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News & Perspectives

Wednesday, November 25, 2015

Source: iStock/KatarzynaBialasiewicz

Horizon Discovery Group said today it has signed development agreements with three undisclosed “global” developers of companion diagnostic tests totaling an initial $3.3 million.

Horizon will develop new and/or supply existing reference standards for the development and validation of new companion diagnostics—as well as for potential inclusion in on-market diagnostic kits under Original Equipment Manufacture (OEM) agreements.

Under the agreements—which include an extension of a pre-existing program—Horizon will provide reference standards for genomic and immunohistochemistry-based standards.

The accuracy and effectiveness of the diagnostic tests will be benchmarked using Horizon’s reference standards, the company said.

“For these prominent diagnostic companies to choose to collaborate with Horizon underlines our expertise and leadership in the creation of reliable diagnostic reference materials, increasingly critical for precise cancer diagnosis,” Horizon Discovery Group CEO Darrin M Disley, Ph.D., said in a statement.

Horizon said the three partnerships are in line with its strategy of generating sustainable, scalable core revenue growth. Reagent development and supply of materials for diagnostic test validation programs provide near-term revenue, while opening up avenues for future OEM relationships.

Those relationships, in turn, deliver visible and predictable revenues as Horizon’s reference standards are integrated into the diagnostic work-flows and kits of partners, according to the company.

Horizon will recognize $3.2 million of revenue from the agreements this year, and the remainder next year.

“These deals are part of larger collaborations with the companies involved and they are expected to lead to additional revenue over time,” Dr. Disley added. “This represents a continuation of our progress in creating a greater network of trusted partnerships and in finding new channels to market for our products.”

Headquartered in Cambridge, U.K., Horizon has more than 1,200 customers across more than 50 countries. According to the company, those customers include major pharmaceutical, biotechnology, and diagnostic companies as well as leading academic research centers.

Horizon’s core capabilities are built around its translational genomics platform, a high-precision and flexible suite of gene-editing tools designed to alter almost any endogenous gene sequence of human or mammalian cell-lines.

Wednesday, November 18, 2015

Source: FDA

The Association for Molecular Pathology (AMP) has urged a U.S. House of Representatives subcommittee to update the Clinical Laboratory Improvement Amendments of 1988 (CLIA)—and thus limit the FDA’s plan to regulate “high-risk” laboratory-developed tests (LDTs).

At a hearing yesterday of the House Energy and Commerce Subcommittee on Health, AMP submitted written testimony calling for the most extensive updates to CLIA since it was phased in starting in 1994.

As it contended earlier this year, AMP says the updated CLIA should be the basis for legislation that would build upon the current system for overseeing the tests, which AMP calls “laboratory developed procedures” or LDPs.

AMP, whose membership includes academic and community medical centers, is among opponents of the FDA’s proposed rules for LDTs. AMP contends that the FDA is overreaching because the tests are not medical devices subject to the Food, Drug, and Cosmetic Act (FDCA).

While FDA first began regulating medical devices in the 1970s, “we chose not to enforce applicable regulatory requirements for LDTs because they were relatively simple tests generally confined to local labs, and often used for rare conditions,” Peter Lurie, M.D., M.P.H., FDA’s associate commissioner for public health strategy and analysis, said Monday in a post on the agency’s blog.

As LDTs have become more complex over the past generation, FDA has argued, many consist of components that are not legally marketed for clinical use while others are used beyond local populations and manufactured in high volume.

The FDA has also raised concerns that many are used widely to screen for common diseases or direct critical treatment decisions; and that many of the tests produce false results, positive or negative.

“FDA oversight would help ensure that tests are supported by rigorous evidence, that patients and health care providers can have confidence in the test results, and that LDTs have more scientifically accurate product labeling,” Dr. Lurie added.

The AMP has countered that the benefits of the FDA’s proposed regulation would be outweighed by its risks, which it said would include additional costs and red tape in the development of new procedures.

“The AMP proposal to enhance oversight over laboratory services does not slow innovation or constrain the flexibility and adaptability of LDPs,” Roger D. Klein, M.D., J.D., AMP professional relations chair, said in written testimony at the hearing, titled “Examining the Regulation of Diagnostic Tests and Laboratory Operations.”

“Most important, it preserves patient access to essential laboratory services provided by academic medical centers, cancer centers, hospitals and health systems, and small independent laboratories that will no longer be offered if a costly FDA-based regulatory system is imposed upon these key health care organizations and the professionals employed by them,” Dr. Klein added.

AMP said its proposal would address stakeholder concerns by:

• Setting standards for adverse event reporting based on effects of laboratory test results on patients.
• Requiring that test information be publicly displayed in a searchable, standardized format for review by physicians, laboratories, and patients.
• Maintaining clinical laboratory oversight under the single agency now charged with overseeing CLIA, the Centers for Medicare & Medicaid Services (CMS).

AMP contrasted the third provision with legislation drafted by the committee, which would assign regulation of “processing” of an LDP to FDA, while placing oversight of performance of and LDP within CLIA.

“It is not clear how processing can be consistently distinguished from performance, or which agency’s rules would govern under specific circumstances,” Dr. Klein said in his testimony. “The Committee’s draft legislation would interfere with the practice of medicine, and if enacted, threatens to concentrate testing in a few large laboratories that are far removed from patients and ordering physicians, disrupting traditional healthcare teams comprised of pathologists, geneticists, oncologists, and other health care providers.”

Wednesday, November 18, 2015

Source: © Photographee.eu/Fotolia

Thermo Fisher Scientific said today it will partner with Novartis and Pfizer to develop and commercialize a companion diagnostic for non-small cell lung cancer (NSCLC) across multiple drug development programs. The value of the collaboration was not disclosed.

The companion diagnostic will be a multimarker, universal next-generation sequencing (NGS) oncology test designed to assess multiple genes simultaneously from a single sample—and thus help match cancer patients with specific drug candidates.

The NGS panel will provide a platform designed to accelerate the development and registration of several new NSCLC drugs and potential new clinical indications for existing drugs, Thermo Fisher Scientific said.

“We look forward to building upon our ongoing collaboration with Novartis and Pfizer to lead the efforts in building potential novel NGS testing approaches to advance the future of cancer care,” Mark Stevenson, president of life sciences solutions for Thermo Fisher Scientific, said in a statement. “The potential to generate a paradigm shift through this agreement—from one test for one drug, to one test for multiple NSCLC therapies, represents a significant step forward in realizing the promise of precision medicine.”

According to the company, the NGS-based companion diagnostic test for NSCLC will be developed using its Ion PGM Dx System and Oncomine assays. Both the NGS platform and Oncomine reagents apply Thermo Fisher’s Ion AmpliSeq™ technology, designed to enable simultaneous sequencing of hundreds of genes, with high reproducibility and rapid turnaround time.

Thermo Fisher added that the Ion Torrent-based sequencing platform and reagents will offer comprehensive sequence analysis of a wider variety of tumor samples, including limited or compromised specimens derived from formalin-fixed paraffin-embedded (FFPE) tissue or fine needle aspirates. DNA and RNA sample input requires a few FFPE slides or 10 ng extracted nucleic acid per reaction.

“It is our hope that we will be able to take advantage of this new technology as part of our growing lung cancer portfolio to offer even better outcomes for patients,” stated Alessandro Riva, M.D., global head oncology development and medical affairs, Novartis Oncology.

Novartis Oncology’s pipeline lists four compounds under study for NSCLC, most in Phases I, II, or combination I/II. Pfizer’s pipeline includes four NSCLC compounds, led by the already-marketed c-MET-ALK-ROS1 inhibitor Xalkori (crizotinib), in registration phase in Europe for a new indication of anaplastic lymphoma kinase (ALK)-Positive 1st Line NSCLC. On October 22, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending the new indication.

Added Hakan Sakul, Ph.D., executive director and head of diagnostics, worldwide R&D, Pfizer: “We believe that this collaboration will help us get closer to our goal of ensuring that cancer patients are able to benefit from a targeted therapy associated with their tumor’s genetic profile.”

Monday, November 16, 2015

Source: iStock/© Chagin

LGC said today it has acquired Maine Standards Company, a provider of calibration verification materials for U.S. clinical laboratories, for an undisclosed price.

Established in 2001, Maine Standards Company specializes in calibration verification/linearity testing, serving the needs of clinical laboratories, and most recently, physician office labs. The company specializes in developing and manufacturing products for calibration verification/linearity, reportable range validation, and new instrument performance validation.

Earlier this year, Maine Standards Company released the VALIDATE® HbA1c calibration verification/linearity test kit; as well as VALIDATE ANEMIA, a calibration verification/linearity test kit designed to measure Ferritin, Folate, and Vitamin B12.

The company manufactures VALIDATE calibration verification/linearity test kits for over 80 analytes, including general chemistries, urine chemistries, enzymes, lipids, HbA1c, therapeutic drugs, cardiac markers, thyroids, serum proteins, vitamin D, prostate specific antigen, and ferritin.

Going forward, LGC said, Maine Standards Company will continue to operate from its recently opened facility near Portland, ME, in Cumberland Foreside, under LGC’s ownership.

London-based LGC said the acquisition will strengthen its growing portfolio of reference materials and proficiency testing programs for the clinical market.

“Our two organizations represent a highly complementary commercial and cultural fit, with a common commitment to developing products of the very highest quality for the benefit of our customers,” Euan O’Sullivan, managing director of LGC’s Standards Division, said in a statement.

“We look forward to working with Maine Standards Company to complete its leading portfolio of calibration verification materials for the US market, while using our global network to expand sales of these products internationally,” O’Sullivan added. “We also see exciting opportunities to combine our distinctive analytical capabilities to develop new products for our mutual customers.”

Added Tom Happe, founder and president of Maine Standards Company: “our combined capabilities will enable us to more easily address the growing global market for our products, at the same time as assisting in our ongoing new product development activities.”

LGC serves customers in pharmaceuticals and a number of other industries, including agricultural biotechnology, food, environment, government, and academia. The company employs more than 2,000 people, and operates in 22 countries worldwide.

Wednesday, November 11, 2015

Results from a new study show the validity of using CSF as a medium for finding ctDNA to detect brain tumors. [Jonathan Bailey, NHGRI]

The field of liquid biopsies has exploded over the past several years with tests being conceived and validated for a large number of widely diverse cancer types. However, for a variety of reasons, liquid screens for brain tumors have been anemic—largely due to the extremely low concentrations of circulating central nervous system DNA within plasma.

Now, researchers at the Vall d’Hebron Institute of Oncology (VHIO) in Barcelona has published evidence validating the use of cerebrospinal fluid (CSF) as a liquid biopsy medium for the potential identification, prognosis, and tracking of brain tumor genomic alterations not in real time prior to and throughout drug treatment regimens. Contrary to low plasma concentration levels, CSF contains very high amounts of circulating tumor DNA (ctDNA).

Using a lumbar puncture—colloquially referred to as a spinal tap— the investigators were able to search for ctDNA corresponding to different brain cancers. The spinal tap procedure, while not pleasant, is much less invasive and risky than standard procedures of obtaining brain tissue for biopsy. Interestingly, the researchers were able to show that the CSF derived ctDNA complemented the diagnosis of leptomeningeal carcinomatosis, a rare brain cancer of the meninges that most often derives from the metastasis of another tumor.  

"We looked for a way to apply this type of liquid biopsy to brain cancer, especially in view of the obstacles associated with accessing this tumor type," explained senior author Joan Seoane, Ph.D., director of translational research at VHIO.

"Our main limitation was that ctDNA levels for brain tumors are very low in plasma,” continued Dr. Seoane. “But the brain has its own closed circuit of fluid, cerebrospinal fluid, which bathes the brain and spinal cord, and is therefore in direct contact with tumor cells and we found circulating tumor DNA in CSF at such high levels that we were able to detect and characterize tumors with a high degree of sensitivity."

The findings from this study were published recently in Nature Communications through an article entitled “Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma.”

"Compared to plasma, cerebrospinal fluid better captures the mutations in patients with brain tumors,” stated lead author Leticia De Mattos-Arruda. M.D., research fellow at VHIO. “The possibility of studying DNA fragments in this fluid by liquid biopsy, as we have done, greatly expands diagnostic possibilities, improves stratification based on genetic profiling, and facilitates better and less invasive monitoring of patients. Our findings should also ultimately translate into clinical benefit for certain patients with brain tumors."

Additionally, the VHIO team was able to detect and confirm the diagnosis of glioblastoma multiforme, the most common and aggressive malignant brain tumor. One of the characteristics of glioblastoma is that the tumor always reappears after time, so the ability to track the progression of this cancer during and after surgery and chemotherapy will become invaluable at getting in front of the disease to prevent it from spreading further.

"Mirroring certain successes to-date of applying liquid biopsy across other tumor types, the use of tumor DNA circulating in CSF as a liquid biopsy for brain tumors could be much less invasive than standard tissue biopsy to characterize the genetic alterations of the new tumor,” remarked co-author Josep Tabernero M.D., director of VHIO and head of the medical oncology department of Vall d'Hebron University Hospital. “This new approach to liquid biopsy in CSF could help, in some cases, to consider novel, more specific and targeted experimental therapies, which could in turn also improve clinical response."

Witnessing the potential of liquid biopsies at research level for so many cancer types, there is every indication that this technique will become a fundamental part of clinical medicine for the future diagnosis and treatment of brain tumors.

“This study of circulating tumor DNA has enabled us to monitor tumors by liquid biopsy of CSF. This approach is, therefore, a potential tool for stratifying patients, assessing their prognoses, and closely monitoring the course of the disease and their response to therapy in a minimally invasive manner," concluded Dr. Tabernero.

Tuesday, November 10, 2015

A study from Karolinska Institutet in Sweden shows that a new test for prostate cancer is better at detecting aggressive cancer than PSA. [Darryl Leja, NHGRI]

Arguably, there are few things men look less forward to than the thought of prostate examination. The reasons for their trepidation range from the comical to somber reality of facing the second most common form of cancer among men worldwide—prostate cancer—with over 1.2 million cases diagnosed in 2012 alone. The uneasiness that many men feel about the screening process, however, is not wholly unjustified, as the main diagnostic used to determine if a patient has prostate cancer, the prostate-specific antigen (PSA) test, has long been controversial due to its high false hit rate.      

However now, a new study led by scientists at the Karolinska Institutet, in collaboration with Thermo Fisher Scientific, shows that a new test for prostate cancer is better at detecting aggressive cancer than PSA. This new screening method has undergone a clinical trial in 58,818 men and was able to detect aggressive cancer earlier, reduce the number of false positives, and decrease the number of unnecessary biopsies.

“PSA can’t distinguish between aggressive and benign cancers,” explained lead author Henrik Grönberg, M.D. Ph.D., professor of cancer epidemiology at the Karolinska Institute. “Today, men who don’t have cancer or who have a form of cancer that doesn’t need treating must go through an unnecessary, painful, and sometimes dangerous course of treatment. On top of this, PSA misses many aggressive cancers. We, therefore, decided to develop a more precise test that could potentially replace PSA.”

To date, no diagnostic test based upon the STHLM3 model has yet been approved for use by the U.S. Federal Drug Administration or other regulatory agencies outside the U.S.

The new procedure, called the STHLM3 test analyzes a simple blood sample from the patient for a combination of six protein markers (PSA, free PSA, intact PSA, hK2, MSMB, and MIC1) and 232 single nucleotide polymorphisms (SNPs), along with clinical data such as age, family history and previous prostate biopsies.

The findings from the study were published today in The Lancet Oncology through an article entitled “Prostate cancer screening in men aged 50–69 years (STHLM3): a prospective population-based diagnostic study.”

The STHLM3 test and PSA were performed on all participants and then compared side-by-side. The results showed that the STHLM3 test reduced the number of biopsies by 30% without compromising patient safety. In addition, the STHLM3 test found aggressive cancers in men with low PSA values (1-3 ng/mL)—which typically go undetected by current methodologies.

"This is indeed promising results. If we can introduce a more accurate way of testing for prostate cancer, we'll spare patients unnecessary suffering and save resources for society", noted Dr. Grönberg. "The STHLM3 tests will be available in Sweden in March 2016, and we will now start validating it in other countries and ethnic groups."

Joseph Bernardo, president of Thermo Fisher’s clinical next-generation sequencing and oncology business, added that “the study authors put this all in perspective by pointing out that a 30% reduction in prostate biopsies would translate to 300,000 fewer procedures annually in the U.S. So, in addition to improving patient experience and outcomes, there is also the potential for significant healthcare cost savings.”

Thursday, November 05, 2015

Source: iStock/© Alex Belomlinsky

A collaborative team of researchers from the Translational Genomics Research Institute (TGen), Mayo Clinic, and Cancer Research UK Cambridge Institute (CRUK) have successfully shown that circulating tumor DNA (ctDNA), shed into the blood stream from cancer cells, can be used to track the progression of cancers and their response to treatment, in real time.

The researchers were able to obtain samples over a three year period from a patient with invasive ductal carcinoma—which had metastasized to other parts of her body. Using these samples the investigators were able to perform extensive analyses and comparisons between traditional biopsy results and those from ctDNA obtained through liquid biopsy methods.       

"When patients receive therapy for advanced cancers, not all parts of the tumor respond equally, but it has been difficult to study this phenomenon because it is not practical to perform multiple, repeated tissue biopsies," explained co-lead author Muhammed Murtaza, M.D. Ph.D., co-director of TGen’s Center for Noninvasive Diagnostics

The results of the study found that the DNA from the blood samples correlated with DNA from the traditional biopsies, reflecting the same pattern and timing of genetic changes as the cancer developed and responded to treatment. The results provide the first proof-of-principle that analyzing tumor DNA in the blood can accurately monitor cancer within the body.

"This definitively shows that we can use blood-based DNA tests to track the progress of cancer in real time,” noted co-senior author Carlos Caldas, M.D., senior group leader at CRUK. “The findings could change the way we monitor patients, and may be especially important for people with cancers that are difficult to reach, as taking a biopsy can sometimes be quite an invasive procedure."

Dr. Murtaza added that "our findings empirically show that ctDNA analysis from blood samples allows us to detect cancer mutations from multiple different tumor sites within a patient and track how each of them responds."

The findings from this study were recently published in Nature Communications through an article entitled “Multifocal clonal evolution characterized using circulating tumour DNA in a case of metastatic breast cancer.”

Additionally, the results from this study suggest that precise and real-time genetic monitoring of changes in a patient's cancer, through ctDNA analysis, could help inform physicians about the type of targeted treatment that might be best at each stage of the disease.

"The potential of using circulating DNA for estimating just how well a patient may respond to targeted therapies and for tracking the development of resistant clones in real-time, heralds a new era for precision medicine," said Keith Stewart, M.B., Ch.B. director of the Mayo Clinic Center for Individualized Medicine, who was not directly involved in the research.

While this study was done in a single patient with a specific type of cancer, the implications from the data the authors obtained may have an invaluable impact on future studies using ctDNA

"We were able to use the blood tests to map out the disease as it progressed. We now need to see if this works in more patients and other cancer types, but this is an exciting first step," stated Dr. Caldas.

"Spotting tumor DNA in the bloodstream is a promising area of research, and has the potential to give doctors valuable clues about a patient's disease without having to take repeated tumor samples,” remarked Kat Arney, Ph.D., science information manager at CRUK. "For now, surgical biopsies still play an important role in diagnosing and monitoring cancers. But this work gives us a window into the future, where we'll use less invasive techniques to track the disease in real time."

Tuesday, November 03, 2015

Source: iStock/tarmofoto

Personalized medicine is usually about personalized benefits. For example, a drug’s potential to benefit a particular patient can be determined on the basis of that patient’s unique genetic make-up, as indicated, for example, by a genomic or metabolomic profile. But what about a drug’s capacity for side effects? If personalized medicine can predict, on a patient-by-patient basis, a drug’s upside, it can, presumably, also predict a drug’s downside.

This notion was put to the test by researchers at the University of California, San Diego. They conducted a proof-of-concept study to demonstrate the feasibility of predicting a drug’s side effects on an individualized basis. Specifically, they developed a predictive model that relied on measurements taken from patients’ blood.

The study was based on genomic and metabolomics data obtained from blood samples of 24 individuals. Researchers used these data to build a personalized, predictive model for each individual. Researchers then used these predictive models to understand—at the metabolic level—why some individuals experienced side effects to ribavirin, a drug used to treat hepatitis C, while other individuals did not.

Details of the study appeared October 28 in the journal Cell Systems, in an article entitled, “Personalized Whole-Cell Kinetic Models of Metabolism for Discovery in Genomics and Pharmacodynamics.”

“[We] constructed multi-omic, data-driven, personalized whole-cell kinetic models of erythrocyte metabolism … based on fasting-state plasma and erythrocyte metabolomics and whole-genome genotyping,” the authors wrote. “We show that personalized kinetic rate constants, rather than metabolite levels, better represent the genotype. Additionally, changes in erythrocyte dynamics between individuals occur on timescales of circulation, suggesting detected differences play a role in physiology.”

While the authors cautioned that their small, proof-of-concept study will need to be confirmed by larger studies, they pointed out that their work demonstrated the feasibility of personalized kinetic models. The authors emphasized, for example, that their modelling efforts not only identified individuals at risk for a drug side effect (ribavirin-induced anemia), but also uncovered a potential protective mechanism (a genetic variation associated with inosine triphosphatase deficiency.

"We're not just interested in predicting the efficacy of a drug, but its side effects as well," said Bernhard Palsson, Ph.D., the Galetti Professor of Bioengineering at the Jacobs School of Engineering at UC San Diego.

"There needs to be a good way to obtain data about a drug's side effects before exposing a lot of people to the drug. This predictive model could be used to figure out what these side effects are ahead of time," added UC San Diego alumnus Aarash Bordbar, who did this research while a Ph.D. student in Dr. Palsson's Systems Biology Research Group.

The researchers stressed that predictive models such as theirs would be extremely useful for pharmaceutical companies during the drug development stage. For example, pharmaceutical companies could conduct predictive screenings for drugs before clinical trials and determine which groups of patients would experience side effects and which ones wouldn't.

"This study is a step forward in demonstrating that patients could be precisely treated based on their genetic makeup," noted Dr. Palsson.

As a next step, researchers are also looking to develop predictive models for platelet cells, which are more complex than red blood cells. The ultimate goal is a liver cell model, researchers said, because the liver is where the majority of drugs are metabolized and where many drug side effects are manifested.

Monday, November 02, 2015

Source: iStock/ CreativeGraphicArts

It seems that the genome’s protein-coding regions get all the attention, but they don’t explain everything, certainly not everything about cancer. In fact, these regions, which account for less than 2% of the genome, are less cancer-type-specific than non-protein-coding regions of the genome. That’s the startling conclusion of a study (“Comprehensive Genomic Characterization of Long Non-coding RNAs across Human Cancers”) that appeared October 12 in the journal Cancer Cell.

The study focused on a particular kind of non-protein-coding DNA, the 70% of the genome that generates long non-coding RNAs (lncRNAs). After analyzing lncRNAs at transcriptional, genomic, and epigenetic levels in over 5,000 tumor specimens across 13 cancer types from The Cancer Genome Atlas (TCGA), the study’s authors found that lncRNA alterations are highly tumor- and cell line-specific compared to protein-coding genes. In addition, these investigators determined that lncRNA alterations are often associated with changes in epigenetic modifiers that act directly on gene expression.

The study’s authors consisted of an international team led by researchers at the University of Pennsylvania. “Our study provides convincing evidence that dysregulation of lncRNAs takes place at multiple levels in the cancer genome and that these alterations are strikingly cancer-type specific,” asserted Lin Zhang, M.D., an associate professor of obstetrics and gynecology. “We expect that additional important lncRNA discoveries will be enabled by our work.”

For the rest of the story, click here.

Monday, November 02, 2015

Source: iStock/fatido

When genomic sequencing is added to a patient’s care, the initial costs can be considerable, but they don’t appear to climb over time. For example, costs related to follow-up tests don’t seem to proliferate. Even the initial costs are mostly due to DNA sequencing itself, not the various activities involved in integrating sequencing into the clinical setting.

These conclusions came from a study that considered only short-term healthcare costs. It did not account for how long-term healthcare costs might be decreased by genomic sequencing, even though genomic sequencing promises to reduce such costs by enabling prevention and early treatment.

The study (“Short-term costs of integrating genome sequencing into clinical care: Preliminary results from the MedSeq Project”) was presented October 9, at the annual meeting of the American Society of Human Genetics (ASHG) in Baltimore. It assumed a third-party payer perspective using medical record data and price weights from Medicare reimbursement schedules.

For the rest of the story, click here.

Monday, November 02, 2015

Source: iStock/valentinrussanov

A new study in the Lancet indicates that Abbott’s ARCHITECT STAT High Sensitive Troponin-I (hsTnl) test may rule out heart attacks to help doctors promptly discharge two-thirds of patients with chest pain from the emergency department. These patients may then avoid a prolonged wait for additional testing or hospital admittance.

This study suggests that by using a newly identified level of troponin, a protein which at increased levels can indicate injury to the heart, doctors may improve patient care by ruling out heart attacks without repeat testing, thereby reducing unnecessary procedures and hospital admissions.

For the rest of the story, click here.

Monday, November 02, 2015

In October 2015, Human Longevity launched Health Nucleus™. [Human Longevity, Inc.]

Human Longevity (HLI) launched Health Nucleus, a genomic-powered clinical research project that the company says has the potential to transform healthcare. The inaugural Health Nucleus facility is located in San Diego at HLI’s headquarters. More Health Nucleus facilities are slated to open in 2016 in other U.S. and international cities.

The Health Nucleus platform uses whole-genome sequence analysis, advanced clinical imaging, and machine learning, combined with a comprehensive curation of personal health history, to deliver a comprehensive picture of individual health.

For the rest of the story, click here.

Graham P. Lidgard, Ph.D.

Monday, November 02, 2015

Patients are often reluctant to undergo colonoscopy. [iStock/Wicki58]

Colorectal cancer is the second-leading cause of death (behind only lung cancer) among men and women in the United States; 49,700 people are expected to die from the disease this year alone.

National screening guidelines call for men and women at average risk for the disease to begin screening at age 50. Unfortunately, while physicians are eager to get their patients screened, 23 million Americans in this age group who are at average risk do not get screened as recommended. As a result, many people are diagnosed in later stages when treatment is difficult and survival rates low.

The challenge for physicians is that, historically, the screening options they could offer patients were limited and often undesirable, making it a challenge to motivate patients to follow through.

Colonoscopy is the standard procedure used to screen for colorectal cancer, and while it’s an effective option, some patients are unwilling to undergo the procedure because it often involves unpleasant preparation, sedation, and time off work.

Additional lab-based tests, such as the fecal occult blood test (FOBT) and fecal immunochemical test (FIT), were developed to help meet the need for noninvasive options and are designed to detect occult blood in the stool. However, because there are unrelated conditions that can cause blood in the stool, and not all polyps or lesions bleed, these tests may not be reliable on their own for the detection of colorectal cancer. In addition, the FOBT has a long list of potential causes for false positive results and a low level of sensitivity, while FIT delivers only a moderate level of sensitivity.

For the rest of the story, click here.

Monday, November 02, 2015

Source: © Dmitry/Fotolia

Tute Genomics said today it has acquired the human-genome interpretation company Knome for an undisclosed price.

Co-founded by George Church, Ph.D., Knome provides human genome interpretation systems and services designed to help researchers, drug developers, and clinicians determine the genetic basis of human disease and drug response.

Knome says its big-data technologies are intended to advance precision medicine by speeding up and industrializing the process of interpreting whole genomes. Most famously, Knome provided genome sequencing and interpretation to Ozzy Osbourne and other high profile early adopters.

Knome's most valuable technology is knoSYS, a best-in-class genome interpretation software platform now in its third generation of development, having originally been conceived as genome analysis software for single human genomes nearly a decade ago.

Tute said it will integrate knoSYS into its cloud-based genome informatics and clinical reporting platform, strengthening its ability to deliver a comprehensive, flexible, scalable, and secure informatics solution for genome-guided medicine.

Tute uses sample-in, report-out technology designed to enable users to process raw sequencing data, perform rigorous quality control measures, annotate genetic variants with more than 200 genetic knowledge sources, and seamlessly create clinical reports. The solution is designed to help diagnostic labs and health systems process next-generation sequencing data quickly and securely.

Technology from Tute has also been integrated with third party tools such as Laboratory Information Management System (LIMS) for scalable sample information management, and electronic health record systems, to bring genetic insights to point-of-care and help guide every medical decisions throughout a patient's life.

“Knome's software is a testament to the extraordinary foresight and ingenuity of its scientists and engineers, as well as the remarkable amount of financial support the company has achieved over the years,” Tute Genomics CEO Reid Robison, M.D., MBA, said in a statement.

“The result is a wealth of technology assets that are well-poised to tackle the bioinformatics challenges faced by healthcare, such as rapidly processing raw genome sequencing data, performing clinical interpretation of the data and generating actionable clinical reports,” Dr. Robison added.

Knome said last year it had closed on a $13 million financing round led by current investors, saying it would use proceeds to promote growth and expansion of its genomic services and software systems businesses.

Tute closed in June on series A1 financing of more than $3.9 million from a group of investors that included Intermountain Healthcare, an integrated network of 22 hospitals and 185 physician clinics. Other major investors included Healthbox, a platform for innovation and entrepreneurship in healthcare, and China-based Internet company Tencent.

Monday, November 02, 2015

Using platelet RNA, scientists have been able to detect the presence of cancer and pinpoint its primary location. [Best et al., 2015, Cancer Cell 28, 1–11]

The age of fast, accurate, and noninvasive cancer screening is rapidly becoming reality. The power of next-generation sequencing has allowed molecular diagnostic techniques to sample small amounts of blood for the genetic hallmarks of tumorigenesis. These liquid biopsy procedures, as they have been dubbed, typically search for circulating tumor DNA (ctDNA) that has made its way into the systemic circulation from tumor cells that have died or enrich for circulating tumor cells (CTCs) that have broken off from the primary cancer site.

Now, a team of researchers lead by scientists at Massachusetts General Hospital (MGH), have developed a new diagnostic test that analyzes the tumor RNA picked up in circulating platelets. The investigators believe this new method could become even more useful than other molecular technologies for diagnosing cancer since it can also determine the primary location of the tumor and provide insight to potential therapeutic approaches.    

"By combining next-generation-sequencing gene expression profiles of platelet RNA with computational algorithms we developed, we were able to detect the presence of cancer with 96 percent accuracy," explains co-senior author Bakhos Tannous, Ph.D., associate professor Harvard Medical School and associate neuroscientist at MGH. "Platelet RNA signatures also provide valuable information on the type of tumor present in the body and can guide the selection of the most optimal treatment for individual patients.

The findings from this study were published recently in Cancer Cell through an article entitled “RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics.”

In the current study the research team describes finding that the RNA profiles of tumor-educated platelets (TEPs)—those that have taken up molecules shed by tumors—can distinguish among blood samples of healthy individuals and those of patients with six types of cancer, determine the location of the primary tumor, and identify tumors carrying mutations that can guide therapeutic decision-making.

Over the past several years, the scientific literature has shown that in addition to their role in promoting blood clotting, platelets take up protein and RNA molecules from tumors, possibly playing a role in tumor growth and metastasis. Dr. Tannous and his colleagues set out to determine whether tumor RNA carried in platelets could be used to diagnose and classify common types of cancer.

The investigators isolated platelets from blood samples taken from 55 healthy donors, 39 individual with early-stage cancer and 189 patients with advanced, metastatic cancer. Among those patients with cancer, they were diagnosed with non-small-cell lung cancer, colorectal cancer, glioblastoma, pancreatic cancer, hepatobiliary cancer, or breast cancer.

The comparison of RNA profiles from the healthy donors to those of the cancer patients identified increased levels of approximately 1,500 RNA molecules—many involved in cancer-associated processes—and a reduction of almost 800 in samples from cancer patients. Using their novel algorithm, the MGH group was able to examine close to 1,000 RNAs from almost 300 individuals with 96% accuracy for the presence of cancer.

Additionally, the platelet mRNA profiles were able to identify the particular type of cancer within each patient participant, including distinguishing among three types of gastrointestinal adenocarcinoma: colorectal cancer, pancreatic cancer, and hepatobiliary cancer. Platelets from patients with tumors driven by mutations in KRAS or EGFR proteins—biomarkers that can guide the use of drugs targeting those mutations—proved to have unique RNA profiles as well.

The researchers were excited by their findings and emphasize the uniqueness of their approach as currently utilized liquid biopsy approaches have been unable to diagnose cancer while simultaneously pinpointing the location of the primary tumor.    

"We observed that the mRNA profiles of tumor-educated platelets have the sensitivity and specificity to detect cancer, even in early, non-metastasized tumors," noted Dr. Tannous. "We are further assessing the potential of TEP-based screening for therapeutic decision making and also investigating how non-cancerous diseases may further influence the RNA repertoire of TEPs."

Douglas S. Rabin, M.D.

Friday, October 30, 2015

Utilization of NIPS is growing, with the market estimated to be $750 million for high-risk pregnancies and up to $3.25 billion when use of NIPS is recommended in medical guidelines for average-risk pregnancies. [iStock/EmiliaU]

In the dozen years since the sequencing of the human genome, the pace of innovation in genetic testing has exploded. We are now able to screen, diagnose, and monitor numerous medical conditions based on insights gleaned from lab tests based on genetic markers identifiable in a blood specimen. For many patients, these diagnostic advances have helped to deliver significantly better care and outcomes than would have been possible a few short years ago.

With this fast rate of advance in gene-based knowledge and innovation, scientists and the medical community must make decisions within a more dynamic—yet ambiguous—environment than ever before. Peering into the human genome is akin to seeking to unravel the depths of the universe. With every new discovery come new questions—and uncertainties. How do we interpret a new piece of genetic information for clinicians? Can we ensure insights into a genetic mutation are actionable for our patients? Genetic advances are fascinating, but they may not always be helpful to delivering better care or outcomes. 

Case in point: noninvasive prenatal screening (NIPS), a field that has experienced rapid growth in the recent years. New screening technologies can help identify a pregnancy affected by an aneuploidy through assessment of cell-free fetal DNA (cfDNA) circulating in the maternal blood stream. Utilization of NIPS is growing, with the market estimated to be $750 million for high-risk pregnancies and up to $3.25 billion when use of NIPS is recommended in medical guidelines for average-risk pregnancies. (As of the summer of 2015, several health plans had adopted NIPS into their policies for average-risk as well as high-risk pregnancies.) 

For the rest of the story, click here.

Gail Dutton

Friday, October 30, 2015

Arivale is taking a personalized genomic approach toward fitness, health,and wellness to create actionable recommendations based on an individual’s goals and genetic background. [iStock/kirstypargeter]

As the benefits of the genomics revolution trickle down to patients, Arivale aims to open the floodgates by providing people with meaningful information they can use to manage their health long before the appearance of illness.

Arivale’s mission goes beyond general advice on diet and exercise. Instead, it analyzes each client’s genome, clinical chemistries, lifestyle, and microbiome to produce specific advice tailored to individuals.

“We can identify genetic variants among individuals that identify which foods will add weight—carbohydrates vs. fats, for example—and how much exercise is needed to effectively lose weight for specific individuals,” co-founder Lee Hood, M.D., Ph.D., says.

Arivale co-founder and CEO Clayton Lewis, a triathlete, has experienced this difference in his own life. For example, his attempt to follow general consumer dietary advice left him discouraged. “I tried the Paleolithic diet,” he recalls, “and I moved slower.”

For the rest of the story, click here.

Stephen C. Peiper, M.D., and Zi-xuan Wang, Ph.D.

Friday, October 30, 2015

Stephen Friend has likened pathologists to the shamans of medicine who use technologies similar to the examination of entrails and divining rods to make important decisions. [iStock/duncan1890]

The dominant paradigm in clinical oncology is personalized (therapeutic) medicine driven by precision diagnostics based on a solid foundation of basic and translational research in oncogenesis and signaling pathways.  It is recognized that malignant transformation occurs through the accumulation of somatic mutations with the ultimate evolution to a malignant tumor that is “addicted” to the signaling programmed by a driver mutation.  Advances in medicinal chemistry have allowed oncologists to directly attack this process with agents specifically targeted to block the oncogenic signaling resulting from the driver mutation, thereby releasing the addiction. 

The success of multiple individual targeted therapies and the inability to make associations between histopathology and somatic genetic mutations has led to an enthusiasm, perhaps quixotic, for genomic diagnosis and has fostered the temptation to consider pathologic diagnoses antiquated.  In fact, Stephen Friend, who cloned the retinoblastoma gene in Robert Weinberg’s laboratory, has likened pathologists to the shamans of medicine who use technologies similar to the examination of entrails and divining rods to make important decisions (He & Friend. Nature Medicine 2001;7:658-9).  The overall result is that current approaches stress aggressive genomic diagnostics and targeted therapies, which are expensive, creating a perfect storm in the current climate of financial efficiency that emphasizes value in medicine.

The critical importance of genomic diagnostics has come to the forefront of clinical research in the form of basket trials in which treatment decisions are based on the detection of actionable driver mutations and are agnostic to pathologic type (including tissue of origin).  Clearly, there have been some therapeutic successes with this approach, such as the effective therapy of hairy cell leukemia (demonstrated in multiple reports, including Dietrich et al. N Engl J Med 2012;366:2038-40) that have the BRAF (V600E) mutation with antagonists that are effective in melanomas that carry this mutation.  There have also been failures, exemplified by the lack of significant clinical responses to these agents in colorectal adenocarcinomas positive for BRAF (V600E).

For the rest of the story, click here.

Jeff Buguliskis, Ph.D.

Friday, October 30, 2015

Prenatal genetic screening based on genomic medical technology increasingly allows for the detection and diagnosis of discreet genetic abnormalities within a clinical setting. [Ernesto del Aguila III, NHGRI]

As one of the more controversial topics in diagnostics today, reproductive genetic testing (RGT) has become a lightning rod for political rhetoric and a font of misconception within the general populace. Science fiction would have us believe that RGT will be used to make designer super babies that are disease free and have perfect features.

However, the current medical reality is seemingly more pragmatic by typically assisting couples with reproductive difficulties obtain genetic screening and counseling during in vitro fertilization (IVF) procedures, as well as help all future parents eliminate the risk of common inherited genetic abnormalities.

Traditional genetic screening techniques have relied on observation methods using either customary histology stains (G-banding stain) for gross chromosomal analysis or the use of specific fluorescent markers (FISH analysis) that hybridize within chromosomes that are common for aneuploidy—defined as an abnormal number of chromosomes within the cell. The advantage of these techniques is their speed, low cost, and validated methods for determining genetic abnormalities. However, to obtain the genetic material often requires the use of invasive techniques that carry some risk for the developing fetus.

Rapid progress in genomic medicine over the past several years has allowed researchers to detect and diagnose discreet genetic abnormalities within a clinical setting. Prenatal genetic screening is a field where this is becoming a mainstay of clinical medicine. Women are routinely administered a variety of genetic screening tests within the first trimester in order to detect chromosomal aneuploidies, as well as other inherited abnormalities. Many of these tests come in the form of ultrasonograms or they use maternal serum markers, which typically suffer from high false positive rates.

Positive tests for fetal abnormalities will often lead to much more invasive methods like chorionic villus sampling (CVS) or amniocentesis. However, many women are uncomfortable with the idea of such invasive procedures, as they carry a 1-2% risk of inducing a miscarriage. However, many companies and institutions have been developing new screening methods that are more accurate and carry much less risk.

For the rest of the story, click here.

Patricia Fitzpatrick Dimond

Friday, October 30, 2015

Pharmaceutical manufacturers have found that using companion diagnostics during drug development improves the success rate of therapeutics being tested in clinical trials. [iStock/anna1311]

Companion diagnostics (CDx), in vitro diagnostic devices or imaging tools that provide information essential to the safe and effective use of a corresponding therapeutic product, have become indispensable tools for oncologists.  As a result, analysts expect the global CDx market to reach $8.73 billion by 2019, up from from $3.14 billion in 2014. 

Use of CDx during a clinical trial to guide therapy can improve treatment responses and patient outcomes by identifying and predicting patient subpopulations most likely to respond to a given treatment.

These tests not only indicate the presence of a molecular target, but can also reveal the off-target effects of a therapeutic, predicting toxicities and adverse effects associated with a drug.

For pharma manufacturers, using CDx during drug development improves the success rate of drugs being tested in clinical trials. In a study estimating the risk of clinical trial failure during non-small cell lung cancer drug development in the period between 1998 and 2012 investigators analyzed trial data from 676 clinical trials with 199 unique drug compounds. 

The data showed that Phase III trial failure proved the biggest obstacle to drug approval, with an overall success rate of only 28%. But in biomarker-guided trials, the success rate reached 62%. The investigators concluded from their data analysis that the use of a CDx assay during Phase III drug development substantially improves a drug’s chances of clinical success. 

For the rest of the story, click here.

Friday, October 30, 2015

The November issue of Clinical OMICs is available now! Check it out by clicking on the link below.

Clinical OMICs Volume 2, Issue No. 11

Thursday, October 29, 2015

A new study utilized electronic medical records and genotype data to reveal three patient subtypes of type 2 diabetes. [iStock/dml5050]

In many ways type 2 diabetes can be compared to cancer, in that it is a multifactorial disease that rarely affects each person similarly. For decades, the medical community has struggled to diagnose and treat type 2 diabetes since it presents with such a vast array of symptoms and associated complications. Moreover, it has long been thought that the disease, like cancer, could be treated more successfully if patients could be grouped into clinically distinct subtypes with more specific prognoses.

Now, a team of researchers from the Icahn School of Medicine at Mount Sinai has used a precision medicine approach to identify clinically and genetically distinct subtypes of patients with type 2 diabetes through the use of a massive data analysis project. The power of this new study lies not only in the possibility of more tailored diagnosis and treatment of type 2 diabetes in the future, but also reveals a novel approach that can be applied to virtually any disease.

The investigators sifted through a complex network of electronic medical records (EMRs) and genotype data for more than 11,000 patients. Patients were grouped into three distinct subtypes based on the EMR data, which was followed by genomic single nucleotide polymorphism (SNP) analysis to pinpoint common genetic variants representative of each subtype.

These subtypes were associated with different clinical characteristics. Patients that were more likely to suffer diabetic nephropathy and retinopathy were placed into subtype 1; cancer and cardiovascular disease in subtype 2; and neurological disease, allergies, and HIV infections in subtype 3. For each subtype, the researchers discovered unique genetic variants in hundreds of genes.

“This project demonstrates the very real promise of precision medicine to improve healthcare by tailoring diagnosis and treatment to each patient, as well as by learning from each patient,” explained senior author Joel Dudley, Ph.D., director of biomedical informatics at the Icahn School of Medicine at Mount Sinai. “It is absolutely efncouraging that we were able to paint a much higher-resolution understanding for a common and complex disease that has long stymied the biomedical community with its heterogeneity. I look forward to seeing what we can accomplish for other patient populations.”

The findings from this study were published recently in Science Translational Medicine through an article entitled “Identification of type 2 diabetes subgroups through topological analysis of patient similarity.”

The impact of this disease cannot be overstated as almost 29 million Americans are afflicted, and diabetes and its complications now rank among the leading causes of death in the United States. Furthermore, diabetes is the leading cause of nontraumatic foot amputation, adult blindness, and the need for kidney dialysis, as well as multiplies the risk of myocardial infarction, peripheral artery disease, and cerebrovascular disease. Globally, the World Health Organization estimates that 8% of the adult population is living with the disease, most unaware that they are affected.

“Our approach demonstrates the potential to unlock clinically meaningful patient population subgroups from the wealth of information that is accumulating in electronic medical record systems. The unique genetic component of this study yielded high-priority variants for a follow-up study in patients with type 2 diabetes,” remarked co-author Ronald Tamler, M.D., director of the Mount Sinai Clinical Diabetes Institute, within the Mount Sinai Health System. “The team’s results suggest an attractive alternative to the kind of large-scale, narrow phenotype studies that have produced limited success in explaining common, complex disease.”

Thursday, October 22, 2015

This is a structure showing EGFR—a cancer driver—in its active dimer conformation. Red indicates mutations that destroy the protein-protein interface. [Eduard Porta Pardo]

Using publically available information from genomic and proteomic databases, a team of scientists lead by researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) have created a new and more comprehensive catalog of driver mutations for cancer. Driver mutations are genes that handle the progression of cancerous growths. The researchers used cancer mutation and protein structure databases to identify mutations in patient tumors that alter normal protein-protein interaction (PPI) interfaces—identifying more than 100 novel cancer driver genes that may help explain how tumors that are driven by the same gene often lead to vastly different clinical outcomes.  

"This is the first time that three-dimensional protein features, such as PPIs, have been used to identify driver genes across large cancer datasets," explained lead author Eduard Porta-Pardo, Ph.D., postdoctoral fellow at SBP. "We found 71 interfaces in proteins previously unrecognized as cancer drivers, representing potential new cancer predictive markers and/or drug targets. Our analysis also identified several driver interfaces in known cancer genes, such as TP53, HRAS, PI3KCA and EGFR, proving that our method can find relevant cancer driver genes, and that alterations in protein interfaces are a common pathogenic mechanism of cancer."

The findings from this study were published online recently in PLOS Computational Biology through an article entitled “A Pan-Cancer Catalogue of Cancer Driver Protein Interaction Interfaces.”

The last several years have seen a massive rise in the collection of “omic” data as well as a push by institutions such as the NIH to encourage data sharing. These efforts have led to an era of extraordinary ability to systematically analyze large-scale genomic, clinical, and molecular data to better explain and predict patient outcomes—all the while hoping to find new drug targets to prevent, treat, and potentially cure cancer.

"For this study we used an extended version of e-Driver, our proprietary computational method of identifying protein regions that drive cancer. We integrated tumor data from almost 6,000 patients in The Cancer Genome Atlas (TCGA) with more than 18,000 three-dimensional protein structures from the Protein Data Bank (PDB)," remarked senior author Adam Godzik, Ph.D., director of the bioinformatics and structural biology program at SBP. "The algorithm analyzes whether structural alterations of PPI interfaces are enriched in cancer mutations, and can, therefore, identify candidate driver genes."

The researchers acknowledged that one of the aims of the current study was to change the mindset and begun to view proteins as multifunctional factories instead of an imposing unknown void, thereby making it possible to identify novel cancer driver genes and propose molecular hypotheses to explain the diverse heterogeneity in tumor populations.   

"Genes are not monolithic black boxes. They have different regions that code for distinct protein domains that are usually responsible for different functions. It's possible that a given protein only acts as a cancer driver when a specific region of the protein is mutated," Dr. Godzik noted. "Our method helps identify novel cancer driver genes and propose molecular hypotheses to explain how tumors apparently driven by the same gene have different behaviors, including patient outcomes."

"Interestingly, we identified some potential cancer drivers that are involved in the immune system,” Dr. Godzik added. “With the growing appreciation of the importance of the immune system in cancer progression, the immunity genes we identified in this study provide new insight regarding which interactions may be most affected."

Wednesday, October 21, 2015

Source: © FotolEdhar/Fotolia

NeoGenomics said today it has agreed to acquire Clarient and its wholly-owned subsidiary Clarient Diagnostic Services from GE Healthcare. The deal, valued at up to $275.2 million, is intended to create a larger and broader provider of precision oncology diagnostics.

NeoGenomics said the acquisition will enable it to expand its offering of cancer diagnostic tests to hospitals and physicians nationwide, as well as speed its growth in the global market for pharmaceutical clinical trials and research.

The buyer said Clarient's pathology services and capabilities in the analysis of solid tumor cancers of the breast, colon and lung were “highly complementary” to its molecular testing services and extensive expertise in testing for hematologic cancers.

NeoGenomics added that the acquisition will allow the combined company to further leverage its existing laboratory facilities and infrastructure to drive productivity and lower operating costs.

“Our vision is to become America's premier cancer testing laboratory, and this acquisition is a major step forward in achieving that vision,” NeoGenomics Chairman and CEO Douglas VanOort said in a statement. “We have always respected Clarient's outstanding capabilities, and are very pleased to be able to combine them with our own outstanding service offering.”

Clarient, a unit of GE Healthcare's Life Sciences business, has approximately 415 employees, and is based in Aliso Viejo, CA, and Houston. Clarient had 2014 revenue of $127 million and adjusted earnings before interest, taxes, depreciation, and amortization or EBIDTA of approximately $13 million.

VanOort said that absent any unexpected changes to reimbursement, Neogenomics expects its 2016 revenue to more than double to approximately $240 million to $250 million.  “Adjusted” EBITDA—not including non-recurring charges and non-cash stock-based compensation expenses—is projected to more than triple to between $33 million and $38 million on a pro forma basis.

He also acknowledged that the combined company will carry out approximately $4 million to $6 million of cost-cutting or “synergies” in 2016. That will grow by the end of year 3, NeoGenomics said, to an expected $20 million to $30 million per year of realized synergies.

“Our increased scale will also enhance our ability to innovate in new areas of precision medicine,” VanOort added. “Of all the possible acquisition candidates we have reviewed, Clarient is by far the best fit for NeoGenomics.”

NeoGenomics will acquire Clarient for $80 million in cash, $110 million in preferred stock, and 15 million shares of NeoGenomics common stock. The stock was valued at about $85.2 million based on Tuesday’s closing share price of $5.68.

The deal is subject to approval by anti-trust regulators and NeoGenomics' shareholders—and is anticipated to close during Q4 of this year.

On a fully diluted basis, assuming full conversion of the preferred stock, NeoGenomics said approximately 32% of the company will be owned by GE Healthcare.

As part of the transaction, NeoGenomics’ Board of Directors will be expanded with the appointment of a new director from GE Healthcare.

NeoGenomics added that it and GE Healthcare have also agreed to collaborate on a new bioinformatics initiative that combines their shared interest in precision oncology.

Wednesday, October 21, 2015

The largest genetic study of eczema ever performed permitted a team of international researchers to identify ten previously unknown genetic variations that contribute to the development of the condition. [University of Gothenburg]

With cold winter temperatures looming around the corner for much of the northern hemisphere, the arid frigid air seemingly brings along with it dry, itchy skin. Yet, for a fair number of people this type of skin malady is a constant part of life, regardless of the season.

Atopic dermatitis—commonly known as eczema—is a common inflammatory skin disorder that affects one out of every five children and between 5-10% of the adult population. While inheritability patterns and some genetic markers have been identified for the disease, most of the genes responsible for the skin condition have yet to be determined.

Now, an international team of scientists from clinical researcher centers across the globe have conducted the largest study to date of atopic dermatitis, pooling data obtained from 377,000 subjects in 40 different projects around the world.     

"We identified ten new genetic variations, making a total of 31 that are currently known to be associated with atopic dermatitis," explained co-author Bo Jacobsson, M.D., Ph.D., professor and chief physician in the department of obstetrics and gynecology at the Sahlgrenska Academy, a division of the University of Gothenburg. "Of particular interest is that each of the new ones has a role to play in regulation of the immune system."

The findings from this study were published recently in Nature Genetics through an article entitled “Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis.”

Among the new candidate genes for eczema, the researchers came upon loci that are important for the innate immune system and for the development and function of T-cells, which play an important role in various immune responses.

“We identified ten new risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with new secondary signals at four of these loci),” stated the researchers. “Notably, the new loci include candidate genes with roles in the regulation of innate host defenses and T cell function, underscoring the important contribution of autoimmune mechanisms to atopic dermatitis pathogenesis.”

Interestingly, the newly identified genetic regions show a robust correlation with known risk loci for other immune disorders such as asthma, allergies, and other chronic inflammatory diseases like Crohn's disease and psoriasis, as well as with autoimmune diseases.

"While the new variations contribute in only a small way to the risk of developing atopic dermatitis, knowing about them will raise our awareness of the mechanisms for the various diseases," noted Dr. Jacobsson. "Our ultimate hope is that additional treatment methods will emerge as a result."

For this study, the researchers incorporated a total of 21,399 cases of European, African, Japanese, and Latino ancestry in 22 different studies comparing them with 95,464 controls. Moreover, the findings were then replicated in 18 studies of 32,059 cases and 228,628 controls.

“While not detracting from the importance of maintaining the skin barrier in the prevention and treatment of atopic dermatitis, our findings lend support to new therapeutic approaches targeted at immune modulation,” concluded the investigators.

Thursday, October 15, 2015

A new study offers a glimpse of the wealth of information that can be gleaned by combing the genome of a large collection of leukemia tissue samples. [hidesy/iStock]

Researchers from the Dana-Farber Cancer Institute and the Broad Institute of MIT and Harvard have harnessed the power of next-generation sequencing to analyze a large collection of leukemia tissue samples. Using whole exome sequencing (WES), the investigators screened genetic material from more than 500 samples of chronic lymphocytic leukemia (CLL) and normal tissue—identifying dozens of genetic drivers for the disease, including two genes that had previously not been linked to human cancer.

The investigators began to trace how some mutations affect the course of the disease and its susceptibility to treatment. Moreover, they started tracking the evolutionary path of CLL, as its dynamic genome spawns new groups and subgroups of tumor cells within a single patient.  

"Sequencing the DNA of CLL has taught us a great deal about the genetic basis of the disease," explained senior author Catherine Wu, M.D., physician at Dana-Farber and associate professor of medicine at Harvard Medical School. "Previous studies, however, were limited by the relatively small number of tumor tissue samples analyzed, and by the fact that those samples were taken at different stages of the treatment process, from patients treated with different drug agents.

Dr. Wu continued, stating "in our new study, we wanted to determine if analyzing tissue samples from a large, similarly-treated group of patients provides the statistical power necessary to study the disease in all its genetic diversity—to draw connections between certain mutations and the aggressiveness of the disease, and to chart the emergence of new mutations and their role in helping the disease advance.  Our results demonstrate the range of insights to be gained by this approach."

The findings from this study were published recently in Nature through an article entitled “Mutations driving CLL and their evolution in progression and relapse.”

The researchers collected tumor and normal tissue samples from 538 patients with CLL, 278 of whom had participated in a German clinical trial that helped determine the standard treatment for the disease. After WES analysis, they uncovered dozens of genetic abnormalities that may play a role in CLL, including 44 mutated genes and 11 genes that were over- or under-copied in CLL cells. Interestingly, two of the mutated genes—RPS15 and IKZF3—have not previously been associated with human cancer. 

"This study also provides a vision of what the next phase of large-scale genomic sequencing efforts may look like," noted lead author Dan Landau M.D., Ph.D., research fellow at Dana-Farber and the Broad Institute. "The growing sample size allows us to start engaging deeply with the complex interplay between different mutations found in any individual tumor, as well as reconstructs the evolutionary trajectories in which these mutations are acquired to allow the malignancy to thrive and overcome therapy."

Another fascinating discovery was that certain gene mutations were particularly common in tumor tissue from patients who had already undergone treatment, suggesting that these mutations help the disease rebound after initial therapy. In addition, the investigators found that therapy tends to produce shorter remissions in patients whose tumors carry mutations in the genes TP53 or SF3B1.

"We found that genomic evolution after therapy is the rule rather than the exception," Dr. Wu remarked. "Certain mutations were present in a greater number of leukemia cells within a sample after relapse, showing that these mutations, presumably, allow the tumor to persevere."

Dr. Wu and her colleagues hope that the findings from their studies will continue the push initiated by precision medicine to help personalize cancer treatments and develop new therapeutics. 

"The breadth of our findings shows what we will be able to achieve as we systematically sequence and analyze large cohorts of tumor tissue samples with defined clinical status," stated co-senior author Gad Getz, Ph.D., director of the Cancer Genome Computational Analysis group at the Broad Institute. "Our work has enabled us to discover novel cancer genes, begin to chart the evolutionary path of CLL, and demonstrate specific mutations affect patients' response to therapy. These discoveries will form the basis for precision medicine of CLL and other tumor types."

Wednesday, October 14, 2015

Source: ©Rido/Fotolia

The HudsonAlpha Institute for Biotechnology said today it has won a $100,000 grant from the Jane K. Lowe Charitable Foundation to help establish a clinical genomics program.

The foundation said the $100,000 will provide funds to support five new HudsonAlpha faculty members “who will work with existing faculty to bring scalable, cost effective, genomic medicine to the residents of Madison County (AL) and beyond.

“The Jane K. Lowe Charitable Foundation is excited that our grant will assist HudsonAlpha to bring genomic medicine to our region and to become a leader in this rapidly developing technology,” said John Wynn, a board member of the foundation. “During her lifetime, Mrs. Lowe was a generous supporter of medical research. This grant enables our foundation to carry on Mrs. Lowe’s legacy by supporting this innovative approach to patient care.”

Each year the Foundation distributes the greater of its net income or 5% of its value, as follows: 60% to six named charities and 40% to charitable organizations chosen by its trustees.

In a separate statement, HudsonAlpha said it has recently recruited the five, which it described as “world-renowned” investigators specializing in genomic medicine who will support the new clinical genomics program.

Next month, HudsonAlpha will open what it said was the world’s first clinic solely for the practice of genomic medicine. The new clinic will make use of HudsonAlpha’s fully-accredited and certified clinical sequencing laboratory, designed to provide clinically-validated and interpreted genomic information for physicians worldwide.

Located in Huntsville, AL, HudsonAlpha carries out genomic data analysis and interpretation toward research into areas that include cancer, undiagnosed childhood genetic disorders, neuropsychiatric disorders, immune-mediated disease, agriculture and public health.

“From the beginning, the mission of HudsonAlpha’s mission has been to utilize the power of genomics to help improve lives. I can’t think of a better way to do that than to use what we know about the genomic sequence to identify the causes of unknown diseases and help identify new therapies for some of the sickest patients,” said Richard M. Myers, PhD, president and scientific director of HudsonAlpha. “We are deeply grateful to the Jane K. Lowe Foundation for this gift.”

Tuesday, October 13, 2015

Source: raven/Fotolia

By declaring unpatentable an isolated nucleic acid containing the breast and ovarian cancer susceptibility gene BRCA1, Australia’s High Court used different legal reasoning than the landmark, two-year-old U.S. Supreme Court decision on gene patentability, in order to arrive at a similar conclusion.

The Australian court on October 7 ruled invalid three patents covering a nucleic acid coding for the BRCA1 protein, with mutations linked to breast and ovarian cancer. Like the Supreme Court, Australia’s highest court’s patent ruling concerned the BRCA1 test developed by Myriad Genetics.

In the latest case, the High Court reasoned that even though the test was in a formal sense a product of human action, the essential element of the invention was not—namely the information stored in the nucleic acid sequences. As a result, the Australian court held, the BRCA1 test did not meet Australia’s “manner of manufacture” standard for patentability.

“Although it may be said in a formal sense that the invention as claimed, referring to isolated nucleic acids, embodies a product created by human action, that is not sufficient to support its characterisation as a manner of manufacture,” according to the court’s majority opinion in the case. “The substance of the invention as claimed and the considerations flowing from its substance militate against that characterisation. To include it within the scope of a “manner of manufacture” involves an extension of that concept, which is not appropriate for judicial determination.”

The ruling was a victory for Yvonne D’Arcy, a 69-year-old pensioner from Queensland, Australia, and two-time survivor of breast cancer. In an interview with Australia’s ABC, she said she was motivated by a desire to help women avoid chemotherapy and radiation therapy by making genetic testing more widely available. She began her legal fight in 2010 when a social-justice law firm took the case on her behalf, then pressed on after an Australian Federal Court judge, and the full Federal Court, both ruled in favor of Myriad.

The Australian High Court ruling was arguably as much of a defeat for test developers as the Supreme Court’s landmark AMP v. Myriad decision (2013)—if not more so.

As with AMP v. Myriad, the Australian decision “appears to tighten the boundaries of patentable subject matter,” Lisa Haile, J.D., Ph.D., a partner at the law firm DLA Piper, told GEN.

There is no reason to believe at this time that the decision will be broadly interpreted, Dr. Haile added, given the narrow question addressed by the Australian court of whether isolated genetic material is patentable. In the U.S., she noted, the Supreme Court’s decision had a significant impact because the decision was taken much further than the question of gene patentability.

“At this time in the U.S., almost all ‘naturally occurring’ subject matter—genes, proteins, cells—are patent-ineligible. For Australia, the concern will be whether this decision will be interpreted more broadly beyond just genes,” Dr. Haile said. “We will need to keep any eye on where the Australian Patent Office and the Australian courts take the decision.”

Unlike the American decision, the Australian High Court extended its definition of unpatentable DNA to include composite DNA (cDNA) and other synthetic genetic material.

“Thus, the High Court decision is potentially more far-reaching than the US Supreme Court’s decision,” Mark Egerton, Ph.D., a principal with the Australian law firm Fisher Adams Kelly, said in a commentary posted on the firm’s website.

Ron Rogers, a Myriad spokesman, told GEN the company does not see the Australian decision as hindering its ability to sell its cancer genetic tests, since the company hasn’t sold many in Australia: “It will have no impact on our business.”

However, in a statement, Myriad expressed disappointment in the High Court ruling, which the company said could hinder development of new genetic tests. Myriad said it invested more than $1 billion over 25 years toward its hereditary cancer testing business and the company has tested more than two million patients to date.

“We remain committed to what we do best, developing innovative and high-quality molecular diagnostic tests that save and improve lives,” Myriad stated. “In order for personalized medicine to become a reality, strong patent protection is essential because it provides the research-based companies like Myriad with an incentive to continue to invest in R&D.”

Sandra Levy

Tuesday, October 06, 2015

The new crop of students will need much more than just a basic understanding of human genetics for optimal patient care, thanks to the remarkable progress in the field of genetics and genomics. [iStock/© sturti]

When Lorraine Potocki, M.D., attended medical school in the 1980s she didn’t have exposure to a genetics class. Dr. Potocki, a professor at Houston, TX-based Baylor College of Medicine’s department of Molecular and Human Genetics, wasn’t even aware that there were training programs in genetics until her residency was well underway. And she didn’t know there was such a thing as clinical geneticists.

Fast forward to 2014: That’s when the first class of medical students graduated from Houston, TX- based Baylor College of Medicine, with a concentration in a genetics track curriculum that Dr. Potocki co-founded with Shweta Dhar, M.D., just  a few years ago.

In addition to three preclinical electives which are available to any med student, the track includes: a Journal Club course for students to discuss key articles in genetics and genomics; an Exome Sign Out Round, where the department meets monthly to discuss patient presentations and whole exome sequencing results from its laboratory; Patients as Teacher program; and a scholarly project which enables student to develop a genetics course.

Albeit a small class, comprised of 15 students, Dr. Potocki believes that offering a genetics track to Baylor’s 180 medical students is essential.  

Make no mistake. The new crop of students nationwide will need much more than just a basic understanding of human genetics for optimal patient care, thanks to the remarkable progress in the field of genetics and genomics, notably the Human Genome Project and the development of genomic-based technologies.

In 1967, Duke University Medical School, Durham, NC launched The Duke University Program in Genetics and Genomics (UPGG), an umbrella graduate training program that spans several basic science and clinical departments and bridges the Medical Center and the College of Arts and Sciences.

The UPGG currently consists of over 100 faculty and adjunct faculty and more than 75 students.

In 1981, Harvard University established the department of genetics at the Medical School. Advances in human genetics had already occurred at its affiliated institutes, including Children’s Hospital and the Massachusetts General Hospital. In its sister faculty in Cambridge, molecular genetics had already produced dramatic discoveries that established the foundation of the science.

Heather C. Mefford, M.D., Ph.D., associate professor, pediatrics division of genetic medicine at University of Washington who has co-chaired the 2nd-year medical genetics course (with Jay Shendure) at the medical school for the past five years, said, “We cover a wide range of topics including the basics of patterns of inheritance, recognizing the ‘red flags’ that suggest a condition is genetic, and taking a good family history. We emphasize the role that genetics plays in both rare and common disease. In the past five years, we’ve added a fair bit of content regarding new technologies for genetic testing—primarily next-gen sequencing for gene panels and whole exome sequencing.”

Dr. Mefford went on to say that incorporating genetics and genomics into the medical school curriculum has never been more important. “Genetic testing is available for disorders across all specialties and all stages of life (prenatal to pediatric to adult). Physicians need to be aware of when and how to send testing and, at the very least, when and to whom to refer their patients for the most appropriate testing and interpretation of results,” said Dr. Mefford.

Gail P. Jarvik, M.D., Ph.D., head of the division of medical genetics, and a professor of genome sciences at University of Washington Medical Center, added, “University of Washington has always been a leader in genetics, so it is no surprise that there has been formal genetics training in the second year of medical school since well before I arrived in 1991.  This content has been updated regularly. Important topics to cover continue to include a taking a proper family history and recognizing family history information should result in consideration of genetic disease, patterns of Mendelian inheritance, and the genetics of common disease, such as cancer and dementia. However, the role of new genetic technologies such as arrays and whole genome sequencing in clinical care now must be included.”

In the fall of 2009, Johns Hopkins School of Medicine fully implemented its Genes to Society curriculum. According to the Johns Hopkins Gazette, the curriculum was nearly six years in the making. The curriculum centers on advances in understanding of the human genome. The changes, some of which have already been integrated into the academic schedule, are grounded in the Human Genome Project and the concepts of human variability, risk and the ability to alter disease presentation and outcomes. Genes to Society also incorporates knowledge in the social and behavioral sciences, as well as public health and policy content, with an aim toward improving societal health outcomes.

In September 2015, Duke University’s School of Medicine created the Center for Statistical Genetics and Genomics. The center, led by Andrew Allen, Ph.D., professor of biostatistics and bioinformatics, will bring together quantitatively oriented scientists from various disciplines on the Duke campus to address the computational and statistical challenges associated with efforts to use genomics to improve patient care.

Albert La Spada, M.D., Ph.D., professor of pediatrics, cellular & molecular medicine, and neurosciences, division head of genetics, department of pediatrics at Rady Children's Hospital-San Diego, and associate director, Institute for Genomic Medicine at University of California, San Diego said, “Medical school education in the U.S. has undergone a transformation over the last 15 years, where the curriculum has moved away from teaching each area of medical science as an individual subject to an integrated approach.  Prior to 2010, the UCSD School of Medicine offered an individual course on ‘Genetics in Medicine’ in December of the first year, but upon reorganization of the curriculum, we decided to include Genetics as one of the core sciences in the ‘Foundations Block’ which comprises the first 1.5 months of education for all entering first year medical students.”

The goal of the genetics course in the Foundation Block is to train the student in principles of inheritance, and provide an introduction to molecular genetics and cytogenetics. The course then provides students with a broad exposure to disease areas where genetics is essential for understanding such disorders, and culminates with an overview of emerging themes in genomic medicine.  To illustrate key issues in medical genetics, students are taught a set of cases from clinical practice in small groups, including diseases such as cystic fibrosis and a developmental disorder diagnosed by genomic sequencing.

If students wish to acquire further training in genetics, they are offered a clerkship in clinical genetics where they will participate in the care of patients.  This clerkship experience will include cases where genomic sequencing is being used to make diagnoses.  Students also have the option of taking a research year where they can participate in biomedical research utilizing emerging genomics techniques.

To be sure, a growing number of large medical school have indeed stepped up to the plate, but adoption of a genetics track, or advanced genetics and genomics courses, is still absent from many med schools’ curriculum.

Recent numbers are hard to come by, but in an Education Report, which appeared in Genetics in Medicine in January 2012, Dhar and a team of researchers noted that over the past several decades many studies have been published demonstrating the deficiency of genetics in the medical school curriculum.

Dhar pointed to a study by Hutner et al., which showed that a major proportion of practicing physicians rely upon their undergraduate and medical education in genetics, and most doctors feel less confident about genetic counseling and testing.

Michael Dougherty, director of education at the American Society of Human Genetics (ASHG), believes that there’s little recent evidence to suggest that the amount of genetics in the med school curriculum has increased “which means that less than half of medical schools incorporate any genetics in the third and fourth years of med school (i.e., the clinical years). Roughly three-fourths teach medical genetics in the basic science first year,” said Dougherty.

ASHG’s executive vice president Joseph McInerney said a recent study showed that medical students who had demonstrated mastery of genetics concepts in their basic science courses could not then apply those concepts during their clinical rotations. “This paper highlights the problem with teaching genetics only in the basic-science years: once the students move into their clinical rotations, there are too few preceptors trained in genetics to help point out and elaborate for students the genetic messages inherent in the clinical cases they encounter,” he said.

David Smith, Ph.D., professor and consultant at Mayo Clinic, believes strongly that med students aren’t receiving the education they need in genetics. “We need to train a whole new cadre of people to be that interface. If students are learning genetics at all, they are learning classical genetics. It’s very much an introduction and it’s not preparing them for this world of (genetics) sequencing at all.”

Dr. Potocki couldn’t agree more. “Our goal is to get all of the medical students literate in genetics. By the time they graduate they should all know about the basic patterns of inheritance, how to take a pedigree, how to navigate a couple of the online genetics resources, such as Genetic Home Reference, and Medelian Inheritance in Man.”

Christopher “Cody” Miller, who is a first year med student at Baylor opted to pursue the genetics track although he says he that he isn’t interested in becoming a clinical geneticist. “I believe that genetics is intrinsic to all areas of medicine. The advent of personalized medicine and all of the research showing that chronic diseases, such as hypertension and diabetes, and all genetic risk factors aren’t necessarily discrete, heredity things, but may predispose you, shows that genetics will play a larger role in medicine,” said Miller. 

Miller said he is especially touched by learning about the genetic conditions of the patients he has met in the track’s Patients as Teachers program.  

Mark Lempert is a patient who participates in this program. After being diagnosed with colon cancer, Lempert was undergoing chemotherapy when his doctor did genetic testing and found that he had a genetic predisposition to his disease. Lempert, who had his colon removed, said that the students are very interested in hearing his story, learning about his genetic condition, and how his diagnosis affects his family’s decision to get tested or not.    

So, with all of the advantages for students and patients that comes with courses in genetics, what are the roadblocks preventing medical schools from jumping on the genetics bandwagon?

One of the barriers facing medical schools is the lack of a huge infrastructure that is necessary for the type of technology that genetics sequencing requires.    

“It’s difficult for places to do this. It’s not a simple thing. It’s not just, okay, you need some sequencing. You have to build an entire superstructure for this technology. You can’t just have a machine that generates data. You need people to analyze data, people to make libraries, you need storage, and you have to have programs that surround it,” said Dr. Smith.

Emphasizing that the technology to sequence genes was born in 2006, but that it has only been used in the clinic setting for a few years, Dr. Smith said a revolution not seen since the development of the transistor, is rapidly occurring not only in med schools, but pharmacy schools. Dubbing it “a pharmacogenomics revolution,” Dr. Smith sees a need for pharmacy schools to develop a genetics curriculum too.

“Now they are measuring some of the P450 enzymes responsible for metabolizing various things. If you are a fast metabolizer it means you have to use more of a drug, if you are a slow metabolizer, less, so pharmacogenomics is becoming very critical in determining how much of a drug you give someone and it is transforming pharmacy,” said Dr. Smith.

The University of Illinois Chicago College of Pharmacy is offering pharmogenomics in its curriculum. Janet P. Engle, Pharm.D., Ph.D., professor and head, department of pharmacy practice, senior associate dean for clinical education at UIC College of Pharmacy, said, “We will be revising our curriculum in fall 2016 and will be adding more content in pharmacogenomics.”  

Pointing out that the Mayo Clinic has a whole series of molecular genetic tests, and over the past decade there has been an explosion from just a few tests to hundreds, Dr. Smith explained that access to a highly competent staff capable of generating and analyzing data is paramount to success in setting up a genetics curriculum.

“It’s just the tip of the iceberg. All of those tests, in the next two years, will transition from Sanger (classical) sequencing to next-gen sequencing. With next-gen sequencing you are sequencing, 10, 50, or 100 or more genes together,” said Dr. Smith.

Having next-gen sequencing also entails creation of a plethora of libraries, and Dr. Smith argues that someone has to be generating the libraries where they are capturing whatever it is you want to sequence and then produce the library and get it ready for the sequencing machine.

Another hurdle med schools face when trying to delve into sequencing technology is the immense cost for the sequencing machines, especially when many of them become obsolete in just a few years. Add to this the fact that there aren’t any reimbursement codes in place, and it’s no wonder that some schools are hesitant to set up a genomics program. 

Having a strong bioinformatics department, which includes a very strong program in research, statistics, and bioinformatics analysis, is one which can serve students well, says Dr. Smith. 

Perhaps Dr. Smith summed up the advantage of med schools offering genetics courses best when he said, “In less than five years more people will have their genome sequenced before they are sick and that information will become part of your medical record. You will be able to tell from genome sequencing what are the cardiovascular, allergy, asthma, and cancer risks. That is also going to transform things.” 

Friday, October 02, 2015

Source: iStock/Mactrunk

Genomic medicine is already demonstrating its valuable uses in pediatric oncology. These uses, however, are mainly limited to diagnostics and risk stratification. Another use, perhaps the most ambitious use, is the development of personalized treatment plans. However, whether or not treatment plans for individual patients can be customized on the basis of genome sequencing data has yet to be demonstrated. Nonetheless, one recent study indicates that genome sequencing may guide treatment decisions and improve patient outcomes.

This study was undertaken by scientists at the University of Michigan Comprehensive Cancer Center and C.S. Mott Children’s Hospital. According to these scientists, the incorporation of integrative clinical genomic sequencing data into clinical management was not only feasible, but also revealed potentially actionable findings in nearly half of the patients; and was associated with change in treatment and family genetics counseling for a small proportion of patients.

These findings appeared in the September 1 issue of the Journal of the American Medical Association, in an article entitled, “Integrative Clinical Sequencing in the Management of Refractory or Relapsed Cancer in Youth,” in which, “clinical sequencing” refers to sequencing of tumor DNA and RNA as well as normal DNA, and “integrative” refers to procedures used to incorporate sequencing into clinical management.

For the rest of the story, click here.

Friday, October 02, 2015

The Percepta Bronchial Genomic Classifier reportedly increases accuracy in diagnosis over that of bronchoscopy alone. [Avrum Spira, M.D., Boston University School of Medicine and Veracyte]

Veracyte said that data supporting the use of its Percepta Bronchial Genomic Classifier to help reduce unnecessary, invasive biopsies as part of lung cancer diagnosis was presented at the recent World Conference on Lung Cancer.

The multicenter study involved 163 current or former smokers undergoing bronchoscopy to evaluate lung nodules or lesions suspicious for cancer. Among the 123 patients whose bronchoscopy results were inconclusive, i.e., meaning that cancer could not be ruled out, the Percepta test identified patients at low risk of cancer with a high level of accuracy (negative predictive value of 94%).
The genomic test and bronchoscopy had a combined ability to detect cancer (i.e., sensitivity) of 96%, compared to 51% for bronchoscopy alone.

For the rest of the story, click here.


Friday, October 02, 2015

Source: DepositPhotos/Bahrialtay

The BRCA1/BRCA2 genetic test for breast cancer may be a very expensive way of looking for needles concealed in massive haystacks. That’s the conclusion reached by UCLA researchers who compared universal BRCA1/BRCA2 screening with alternative diagnostic techniques such as annual mammograms, biennial mammograms, and mammograms augmented by magnetic resonance imaging. The alternatives, the researchers found, are usually more cost-effective than BRCA1/BRCA2 screening.

The basic problem is one of weighing the health benefits of population-based screening against the potential health benefits, a problem which is often resolved by means of decision-analytic modeling. A version of this technique was applied to BRCA1/BRCA2 screening by Patricia Ganz, M.D., director of the division of cancer prevention and control research at UCLA’s Jonsson Comprehensive Cancer Center, and Elisa Long, Ph.D., assistant professor at the UCLA Anderson School of Management. These researchers outlined their work in a viewpoint that was published September 3 in JAMA Oncology.

The viewpoint—“Cost-effectiveness of Universal BRCA1/2 Screening: Evidence-Based Decision Making”—concluded that the BRCA genetic test most widely used today is too expensive to warrant universal screening given how rare BRCA mutations are in women. This test, marketed by Myriad Genetics, sells for about $4,000.

For the rest of the story, click here.

Friday, October 02, 2015

New test detects DNA fragments that are shed from cancer cells and released into the bloodstream. [iStock/ElementalImaging]

Pathway Genomics launched its first liquid biopsy, CancerIntercept™, a noninvasive screening test designed for early cancer detection and monitoring.  The test detects mutations that are commonly associated with lung, breast, ovarian, colorectal cancers, and melanoma, as well as mutations that occur less frequently in other cancer types (such as pancreatic, head and neck, thyroid, gastric, and prostate cancers).

The test is offered for two general populations; CancerIntercept Detect is designed to detect tumor DNA in high-risk, but otherwise healthy, patients while CancerIntercept Monitor monitors patients with active or previously diagnosed cancer. According to Jim Plante, CEO and founder of Pathway Genomics, both programs use advanced DNA analysis to identify small DNA fragments that are shed from cancer cells and released into the bloodstream. The tests analyze the presence of 96 frequently occurring DNA mutations in nine cancer genes.

“Early detection is the single most important factor in ensuring successful treatments and improved survival rates,” said Plante. “Cancer patients and those at risk for the disease can take proactive steps to safeguard their health and fight back against some of the most virulent forms of the disease.”

For the rest of the story, click here.

Kyra Mumford, Ph.D.

Thursday, October 01, 2015

The Parsortix CTC isolation system.

In 1971, President Nixon signed the National Cancer Act, declaring a War Against Cancer. Over the past 30 years, there has been an explosion in molecular oncology with consequent clinical approval of anticancer drugs targeted at specific molecules. The power of drugs, such as trastuzumab, bevacizumab, and gefitinib has resulted in substantially increased patient survival. However, the impact of these drugs continues to be restrained.

Tumor heterogeneity and cancer evolution lead to high relapse rates, and tumors that initially show response frequently develop resistance to initial therapies. Consequently, a major unmet clinical need today is the temporal molecular characterization of cancer. Clinicians require new methods to deploy molecular techniques in initial diagnosis and niche characterization of tumors and for ongoing monitoring of cancer evolution, drug resistance, and relapse. This requires noninvasive methods of biopsy to enable repeated examination of patients to determine the on-going evolution and the progression of their disease.

For the rest of the story, click here.

Stephen C. Peiper and Zi-xuan Wang

Thursday, October 01, 2015

Source: Wikicommons/Oliver Byrne’s Elements of Euclid, 1847

Those of you who have a working knowledge of applied Latin can do a quick and easy translation and deduce that pons asinorum literally means the “bridge of donkeys.” Traditionally, it refers to the proof of the isosceles triangle theorem in Euclid’s Elements, and connotes a challenge that separates the nimble thinkers from the simple minds. The goal of this gazette will be to provide insights that will help us all function as nimble thinkers in the rapidly evolving field of diagnostic genomics.

Multiple significant updates/advances have occurred in the field of lung cancer during the past weeks. The American Society of Clinical Oncology (ASCO) updated guidelines for advanced stage non-small cell lung cancer (NSCLC) diagnosis that have an impact on the clinical genotyping of these tumors and basic science studies elucidated mechanisms in ALK signal transduction that can impact efficacy of targeted therapeutics and the emergence of resistance. The increased understanding of ALK signaling mechanisms provide insights for therapy for targeting multiple critical elements in EML4-ALK positive NSCLC tumor cells.

Guidelines for the selection of patients with NSCLC for treatment with tyrosine kinase inhibitors (TKI) of the epidermal growth factor receptor (EGFR) and the anaplastic lymphoma kinase (ALK) published in November 2014 (Leighl et al. J Clin Oncol 2014;32:3673-9) broadened the spectrum of testing to detect sensitizing mutations in EGFR and activating rearrangements of tyrosine kinases associated with responsiveness to these agents. In addition to testing of tumors from patients with advanced disease (stage IV), characterization of the status of EGFR and ALK genes in patients with stage I, II, and III disease was encouraged. In addition, the importance of testing for rearrangements in other genes encoding tyrosine kinases, specifically ROS and RET, each of which occur in approximately 1% of patients, was recognized.

For the rest of the story, click here.

Alex Philippidis

Thursday, October 01, 2015

The FDA wants to assign LDTs a risk classification of low, moderate, and high, based on existing classes of medical devices. [iStock/Kasto80]

A year after the FDA proposed regulating “high-risk” laboratory-developed tests (LDTs) along the lines of Class III medical devices, through draft guidances friendlier to for-profit diagnostic developers than nonprofit academic medical centers, both sides have advanced detailed regulatory counterproposals in hopes of swaying the agency.

The Association for Molecular Pathology (AMP), whose membership includes academic and community medical centers, has released its own recommended rules for LDTs. AMP contends that the FDA is overreaching in its proposed regulation of LDTs—which it calls “laboratory-developed testing procedures”—because the tests are not medical devices subject to the Food, Drug, and Cosmetic Act (FDCA).

Instead, the AMP is advocating the most extensive updates to the Clinical Laboratory Improvement Amendments of 1998 (CLIA) since they took effect in phases through 1994, with the goal of accommodating current laboratory practices and technology. Labs may develop and use their own diagnostic tests internally, without FDA oversight, if certified under the waiver program of CLIA, overseen by the Centers for Medicare and Medicaid Services (CMS).

The AMP’s “Proposal for Modernization of CLIA Regulations for Laboratory Developed Testing Procedures” creates a three-tier, risk-based regulatory system for LDTs. Labs can validate “low risk” tests and put them into service, subject to inspection in the normal course of the inspection process.

For the rest of the story, click here.

Ian Clift, Ph.D.

Thursday, October 01, 2015

The Genome in a Bottle Consortium has developed the world’s first well-characterized whole human genome reference material. [Genome in a Bottle Consortium]

When people talk about the $1,000 genome, they are not speaking about the whole genome, but the exons, the so-called coding regions of the genome. “Six years ago, I was spending $15,000 per exome sequence,” says Gholson Lyon, M.D., Ph.D., a genomic scientist working for the Cold Spring Harbor Laboratory. “Now that costs about $700.”

Whole genome sequencing is more expensive. “We are still not at the $1,000 genome in my opinion,” Dr. Lyon continues. “Almost everyone I’ve talked to is charging $1,500–2,000, and we pay $3,000 because that gets us 60× coverage of the genome, which we have shown is very important to recover small insertions and deletions in the genome ranging in size from 5 to 50 base pairs.”

Dr. Lyon, who studies rare but heritable medical diseases such as Ogden syndrome and TAF1 syndrome, believes that advances in next-generation sequencing technology—better software algorithms, improved methodologies, and lower costs—accelerate his work and the work of others conducting clinical research.

For the rest of the story, click here.

Jeff Buguliskis, Ph.D.

Thursday, October 01, 2015

Beating cancer depends on early detection. Predictive diagnosis could improve survival rates dramatically. [iStock/Wildpixel]

On a cold December day in 1971, Richard M. Nixon, the 37th president of the United States, signed a bill in front of a packed White House room and proclaimed that it was “an early Christmas present for the American people.”

That bill was The National Cancer Act. Outlined in the document were plans to create a new research infrastructure with enormous resources devoted to fighting the disease. The media quickly dubbed it “Nixon’s War on Cancer.”

However, Nixon was initially reluctant to partition money into a large public health bill and, in fact, originally planned to cut the budget for cancer research. Yet, with continued pressure, especially from individuals such as health activist and philanthropist Mary Lasker and her eponymous foundation, President Nixon made his case in front of the American people during his January 1971 State-of-the-Union Address.

“The time has come in America when the same kind of concentrated effort that split the atom and took man to the moon should be turned toward conquering this dread disease,” President Nixon declared. “Let us make a total national commitment to achieve this goal.”

Brimming with jubilation from having put two men on the moon just a few years earlier, political bluster knew few boundaries, and many pontificated about cancer’s cure by the time the bicentennial had rolled around. Now, more than 45 years later, the public continues to ask where the cure is and what is to show for the money that has been spent.

For the rest of the story, click here.

Thursday, October 01, 2015

Researchers have identified a protective allele that was found to reduce the risk of severe malaria by almost 40% in children. [iStock/© MShep2]

The protective effect of the sickle cell allele and its increased prevalence in sub-Saharan Africa is evidence of the selection pressure that malaria has had on human evolution. However, remarkably few other polymorphisms have been observed to be associated with parasite resistance in large population studies.      

Now, researchers with MalariaGEN—an international network of scientists and clinicians spread across Africa, Asia and other malaria-endemic regions of the world, largely funded by the Wellcome Trust—conducted a genome-wide association study (GWAS) to try and explain why in endemic regions some children develop severe malaria and others do not.

Comparing the DNA from 5,633 children with severe malaria with the DNA of 5,919 children without severe malaria, investigators identified a locus that may explain the disparity in the development of severe malaria. To be certain of their initial results, the scientists replicated the study in a further 14,000 children. 

The new locus identified was near a cluster of genes that code for proteins called glycophorins that are involved in the malaria parasite's invasion of red blood cells. Though many different malaria resistance loci have been postulated over the years, this is one of very few that have stood up to stringent testing in a large multi-centre study; the others include the genes for sickle cell and the O blood group.

"We can now say, unequivocally, that genetic variations in this region of the human genome provide strong protection against severe malaria in real-world settings, making a difference to whether a child lives or dies,” explained co-senior author on the study Dominic Kwiatkowski, M.D., professor at the Wellcome Trust Sanger Institute and the Wellcome Trust Centre for Human Genetics. "These findings indicate that balancing selection and resistance to malaria are deeply intertwined themes in our ancient evolutionary history.

The findings from this study were published recently in Nature through an article entitled “A novel locus of resistance to severe malaria in a region of ancient balancing selection.”

"This new resistance locus is particularly interesting because it lies so close to genes that are gatekeepers for the malaria parasite's invasion machinery,” stated Dr. Kwiatkowski. “We now need to drill down at this locus to characterize these complex patterns of genetic variation more precisely and to understand the molecular mechanisms by which they act."

The researchers found that the protective allele was found most commonly among children in Kenya in East Africa and reduced the risk of severe malaria by about 40% in Kenyan children, with a slightly smaller effect across all the other populations studied.

"These findings provide new insights into the human and Plasmodium genetic interaction that are determined by their co-evolution,” noted co-author Ogobara Doumbo, Ph.D., professor at the Malaria Research and Training Center at the University of Bamako in Mali. “How these findings could be used in public health settings, as a marker of individual and population risk of malaria infection is the next step. Applying the findings in this way will only be possible by training a critical mass of African scientists in genomics and big data management and analysis.”

Researchers have known for decades that the glycophorin cluster of genes is highly variable, but until recent advances in next-generation sequences it was not possible to show that this genetic variation was responsible for protecting people against severe malaria.

Interestingly, the new genetic resistance locus lies within a region of the genome where humans and chimpanzees have been known to share particular combinations of DNA variants, known as haplotypes. This would indicate that some of the variation seen in contemporary humans has been present for millions of years.

"This work is an excellent example of how genuine large-scale collaboration can tap into the power of modern genomic science,” stated co-author Kevin Marsh, M.D., professor at the Kemri-Wellcome Research Programme in Kilifi, Kenya. “The risk of developing severe malaria turns out to be strongly linked to the process by which the malaria parasite gains entry to the human red blood cell. This study strengthens the argument for focusing on the malaria side of the parasite-human interaction in our search for new vaccine candidates.” 

Thursday, October 01, 2015

Source: © Dana Britton/Fotolia.com

Amoy Diagnostics and Illumina are embarking on a collaboration to speed up the adoption of precision medicine and targeted therapies in China.

Amoy will develop and commercialize a series of oncology-related tests based on Illumina's next-generation sequencing (NGS) platforms, including the recently released research-use-only TruSight Tumor 15 as transferred from Illumina to Amoy. The collaboration mirrors the commitment made by both companies to offer integrated solutions to meet China’s clinical needs.

"Our genetic tests for detection of EGFR, KRAS, NRAS, and BRAF mutations, and ALK and ROS-1 fusions, have led the way for precision medicine adoption in clinical oncology across China. However, as the number of clinically actionable genetic variants in cancer increases, NGS technology is crucial in order for companion diagnostics to keep pace. Illumina is the world-leader in NGS and a natural partner for our company. We intend to combine Amoy's expertise in molecular diagnostics with Illumina's superior NGS technology to better serve Chinese cancer patients," said Dr. Limou Zheng, CEO and president of Amoy Diagnostics, in a statement.

Commenting on the strategic collaboration, Dr. Rick Klausner, senior vice president and chief medical officer of Illumina, said in a statement, “We are excited to announce this strategic collaboration with Amoy, which will increase access to our advanced NGS technology in the clinical oncology market in China. Genetic changes are a major cause of cancer development, and the number of clinically actionable genomic variants is growing rapidly. NGS technology, with its ability to generate and analyze large-scale data and its high sensitivity in detecting rare mutations, has shown great value and potential for oncology. Working with market leaders such as Amoy is central to Illumina's strategy to advance personalized cancer diagnostics globally."


Thursday, October 01, 2015

The October issue of Clinical OMICs is available now! Check it out by clicking on the link below.

Clinical OMICs Volume 2, Issue No. 10

Wednesday, September 30, 2015

Source: © AlexRaths/iStock

Today Color Genomics unveiled the Benefits Program for Genetic Testing for Breast and Ovarian Cancer Risk, a first-of-its-kind initiative to offer this type of testing to an organization’s employee base.

The initial partners include 18 organizations from the Bay Area and surrounding area, who are pledging to offer their employees the Color Benefits Program.

The program will cover at least 50% of the cost of the physician-ordered Color Test for employees from October 2015 through October 2016. Color Genomics welcomes others to join in support of Breast Cancer Awareness Month.

Color Genomics launched in April 2015 to offer the Color Test: a clinical-grade, physician-ordered genetic test for 19 genes, including BRCA1 and BRCA2, which are related to breast and ovarian cancer.

All Color testing includes genetic counseling at no additional cost.

For companies participating in the Benefits Program, Color Genomics will also offer onsite educational programs with board-certified genetic counselors. Genetic testing for breast and ovarian cancer risk can typically cost as much as $4,000.

Color’s price for the Color Test is $249, and with a 50% or more subsidy from employers, the fee is $125 or less for employees. In addition, during October’s Breast Cancer Awareness Month, the cost will be about $199.

The pioneering 18 organizations participating in the Color Benefits Program include: Addepar, Andreessen Horowitz, AngelList, CloudPhysics, Gainsight, Glow, Innovation Endeavors, Instacart, Medium, Sacramento Kings, Slack, Social Capital, Stripe, SurveyMonkey, Visa, and Y Combinator.


Wednesday, September 30, 2015

Source: © Ljupco Smokovski/Fotolia.com

Generex Biotechnology has agreed to acquire for $15 million a 51% majority equity interest in Hema Diagnostic Systems (HDS), but could reap up to $50 million in royalties from gross sales of HDS tests, the companies said today.

While saying it entered into a non-binding letter of intent for the majority stake in HDS, Generex cautioned that discussions between the companies are at an early stage, and the deal is pending valuation and other due diligence.

HDS has designed, engineered, and manufactured a series of new rapid diagnostic tests for infectious diseases that include hepatitis B, hepatitis C, malaria, HIV, tuberculosis, syphilis and dengue. As part of the deal, Generex will receive royalty payments on gross sales of HDS products. Those royalties will be capped at $50 million.

All HDS rapid tests are manufactured under GMP conditions and in accordance with ISO13485 guidelines, according to the company.

HDS is also developing new diagnostic tests for chikungunya and Zika Virus—as well as an anthrax test designed to detect both the protective antigen and the lethal factor in 15 minutes from a single drop of blood; and a fourth-generation HIV test designed to detect the presence of HIV in a patient weeks earlier than the current 3rd Generation diagnostic.

In addition, HDS has begun development of a new rapid whole blood Ebola test for in-field and clinical use, with the company citing relationships it has developed in West Africa.

Also, HDS is finalizing a new rapid tuberculosis (TB) assay that will not react to the Bacillus Calmette–Guerin vaccine, and based upon test results will become a triage test confirming the presence of the active/infectious form of m.tuberculosis in a test subject. Upon successful submission of data derived in a series of classified evaluations, the diagnostic will become the first accepted whole blood rapid test for the detection of m.TB in the active/infectious state, according to HDS.

The new TB and Ebola tests, as with the rapid tests, will use HDS’ RAPID 1-2-3® HEMA EXPRESS® system, designed to restrict the free flow of the blood sample by directing it onto an absorbent pad, then directly into a sealed transparent housing. The system virtually eliminates the need for transport of potentially infected blood from the in-field test site to the clinical lab, according to HDS.

HDS's rapid HIV assays have been approved by the U.S. Centers for Disease Control and Prevention (CDC) and are included on the USAID Blanket Waiver List. This enables organizations around the globe to procure the tests with funds under The U.S. President's Emergency Program for AIDS Relief, known as PEPFAR. HDS is also a supplier of product to The Global Fund and to The Partnership for Supply Chain Management.

"We believe that the HDS infectious disease detection technologies can form a synergistic adjunct to the Antigen Express proprietary infectious diseases vaccine platform technology, with prospects for efforts on the Ebola virus as well as avian and swine influenzas, where Antigen Express has already undertaken clinical work, creating new and expanded market opportunities for us both,” HDS President and CEO Lawrence Salvo said in a statement.

Generex develop immunotherapeutic vaccines for malignant, infectious, allergic, and autoimmune diseases through its Antigen Express wholly-owned subsidiary, which has pioneered the use of specific CD4+ T-helper stimulation technologies in immunotherapy. One technology focuses on modification of peptides with Ii-Key to increase potency, while a second relies on inhibition of expression of the Ii protein.

“We look forward to embarking on this exciting new endeavor, an opportunity to leverage the scientific work already undertaken by Antigen Express in vaccines for infectious diseases and to access the presence and experience of Hema Diagnostic Systems in the international marketplace,” added Mark Fletcher, Generex’s president and CEO.

Wednesday, September 30, 2015

A new test developed at Washington University School of Medicine in St. Louis can detect virtually any virus that infects people and animals, including the Ebola virus (above). [Courtesy of The National Institute of Allergy and Infectious Diseases]

Scientists at the University of Washington School of Medicine in St. Louis have devised a new metagenomics shotgun sequencing approach that they believe has the capacity to detect virtually any virus that infects people or animals.

Thousands of different viruses are known to cause illness, but making a diagnosis can be an arduous task requiring a battery of different tests—mainly due to the insensitivity of current methods to detect low levels of viral genetic material.  

"With this test, you don't have to know what you're looking for," explained senior author, Gregory Storch, M.D., professor of pediatrics at WUSM. "It casts a broad net and can efficiently detect viruses that are present at very low levels. We think the test will be especially useful in situations where a diagnosis remains elusive after standard testing, or in situations in which the cause of a disease outbreak is unknown."

The findings from this study were published online recently in Genome Research, through an article entitled “Enhanced virome sequencing using targeted sequence capture.”

Researchers found that with their new test, which they have dubbed ViroCap, they can detect viruses not found by standard testing based on genome sequencing. The new test could be useful for detecting outbreaks of pathogenic viruses such as Ebola, Marburg, and severe acute respiratory syndrome (SARS), as well as more routine viruses, including rotavirus and norovirus, both of which cause severe gastrointestinal infections.

ViroCap sequences and detects viruses in patient samples and is just as sensitive as the gold-standard PCR assays that are widely used in clinical laboratories. However, even the most expansive PCR assays can only screen for up to about 20 similar viruses at the same time.

In the current study, the researchers evaluated their new method in biological samples (blood, stool, and nasal secretions) from patients at St. Louis Children’s Hospital. In one group, standard testing that relied on genome sequencing had detected viruses in 10 of 14 patients. But the new test found viruses in the four children that earlier testing had missed. Standard testing failed to detect common everyday viruses: influenza B, a cause of seasonal flu; parechovirus, a mild gastrointestinal and respiratory virus; herpes virus 1, responsible for cold sores in the mouth; and varicella-zoster virus, which causes chickenpox.  

Additionally, in another group of children with unexplained fevers, standard testing had detected 11 viruses in the eight children evaluated. But the new test found another seven, including a respiratory virus called human adenovirus B type 3A, which usually is harmless, but can cause severe infections in some patients.

After assessing all of the data from the study groups the number of viruses detected jumped from 21 using the standard testing method to 32 viruses detected using the ViroCap method—a 52% increase.

"The test is so sensitive that it also detects variant strains of viruses that are closely related genetically," noted lead author Todd Wylie, instructor of pediatrics at WUSM. "Slight genetic variations among viruses often can't be distinguished by currently available tests and they complicate physicians' ability to detect all variants with one test."

ViroCap targets stretches of DNA or RNA from every known group of viruses that infects humans and animals. In all, the research team included 2 million unique stretches of genetic material from viruses in the test. These stretches of material are used as probes to capture viruses in patient samples that are a genetic match. The matched viral material is then analyzed using high-throughput next-gen sequencing.

"It also may be possible to modify the test so that it could be used to detect pathogens other than viruses, including bacteria, fungi, and other microbes, as well as genes that would indicate the pathogen is resistant to treatment with antibiotics or other drugs," concluded co-author Kristine Wylie, Ph.D., assistant professor of pediatrics at WUSM.

Monday, September 28, 2015

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Cynvenio Biosystem and ATGen Global are poised to bring ATGen’s NK Vue™ test to the U.S. market, as a result of a collaborative partnership.

NK Vue is an ELISA-based blood test that measures Natural Killer (NK) cell activity. NK cells are part of the innate immune system and represent the first line defense against infections and cancer.

Abnormally low levels of NK cell activity have been associated with an increased risk of cancer and autoimmune diseases. Recent publications have described a strong relationship between NK cell activity and the degree of circulating tumor cells in patients with metastatic prostate, breast, and colorectal cancer.

NK Vue, which is already approved to measure Natural Killer cell function in Korea and Canada by their respective regulatory agencies, will be sold in the U.S. as a laboratory developed test (LDT) that has been certified by Cynvenio’s CLIA and CAP-accredited laboratory.

Using the test, U.S. physicians will be able to monitor overall immune wellness in the general population, have a complementary tool in cancer screening and cancer surveillance post-treatment, and be provided with additional insights into the condition of active autoimmune diseases, such as multiple sclerosis and inflammatory bowel disease.

Clinical trials are planned or underway in Korea, Canada, Denmark, China, and the United States looking at the use of NK Vue to monitor several different cancer types, including breast, prostate, lung, colorectal, ovarian, and gastric cancers. In addition, several trials are ongoing to measure NK cell activity in autoimmune diseases and to correlate this with response to treatment and relapse.

Commenting on the collaboration, Dr. Paul Y. Song, chief medical officer at both Cynvenio and ATGen said in a press statement, “An extensive amount of published scientific and clinical research has established the role of NK cell activity in numerous cancers and autoimmune diseases. The problem has been that, up to now, the techniques used to measure NK cell activity have not been easily reproducible or commercially available. We are confident that NK Vue will provide a consistently reliable and affordable means to measure NK cell activity, while spawning new studies that will result in clinically relevant associations with a wide range of diseases not yet explored.”

Friday, September 25, 2015

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Americans are hungry to learn the makeup of their DNA, but their doctors aren’t necessarily having a tete a tete about genetic screenings, according to a recent Counsyl survey.

The survey, conducted by ORC International, among 1,020 adults found that more than half (53%) of consumers are eager to find out what’s in their DNA. Although 94% of adults believe you should do genetic screening, only 7% mentioned that their doctor has discussed genetic screening. What’s more, 41% of respondents said their doctor has discussed family history with them.

According to the survey, the perceived benefits of knowing about potential health problems and any impact on future generations outweighs the fear or anxiety of finding out, with only 11% of respondents saying they would be scared to find out what’s in their DNA and more than half wanting to find out.

The survey also found that most consumers aren’t aware that the right time to do genetic screening is before starting a family. In fact, 78% of respondents indicated that they know that DNA can inform them if they could pass on genetic diseases to their children, and 70% want to glean if they could pass on a genetic disease. However, only 28% of respondents think screening should be done before deciding to start a family.

“Just like family characteristics, such as hair and eye color, people can inherit genetic diseases from their parents. In fact, two people who are carriers for the same condition have a one in four chance of passing the disease to their children. Pursuing genetic screening before getting pregnant gives couples important knowledge that can make a difference for a family’s well-being,” said Shivani Nazareth, director of Women’s Health at Counsyl.

“In most cases where children are born with severe inherited diseases, there was no ‘family history’ known,” added Dr. Jim Goldberg, chief medical officer at Counsyl.  “It’s only when two individuals carry a gene for the same disorder that they are at risk of having an affected offspring and only with carrier screening can we identify these couples.”

Millennials give more thought to finding out what’s in their DNA than their older counterparts. Of respondents aged 18 to 24, 84% have thought about finding out what’s in their DNA. Of those who’ve considering genetic screening, 76% want to know their results. This is in contrast to 44% of respondents over age 65 who have considered genetic screening and only 32% of those respondents who would want to know results.

When queried why they wouldn’t want to find out if they have a genetic disease or could pass on a genetic disease to their future children, 35% of respondents said, I believe what’s meant to be will be; 18% would rather be in the dark; cost was an issue with 16%; having no family history of genetic disease was cited given by 15%, while 12% are just too nervous to find out. Nine percent of respondents indicated they’ve heard that the results are often inaccurate.

After being told that if you test positive for a genetic disease, you can take steps to potentially prevent the disease, or at least detect it at an earlier state when treatment may be more successful, respondents were asked, Does knowing this influence your opinion about genetic screening?  Four in five respondents (80%) stated that their opinions about genetic screening were influenced by the idea that early detection of a genetic disease can help prevent the disease, or at least detect it earlier when treatment may be more successful. Half (51%) find it comforting to know that they would be able to take action against a possible problem, while three in ten (29%) said they want to live a long healthy life and any information is good information. Women and younger respondents are more likely to be influenced by this information.

Finally, when asked, Would you want to find out if you have a genetic disease or could pass on a genetic disease to your future children? 68% of males and 72% of females said yes, and 32% of males and 28% of females gave thumbs down to the idea.

Thursday, September 24, 2015

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AC Immune will partner with the Nestlé Institute of Health Sciences (NIHS) to develop a new minimally invasive Tau diagnostic assay for early diagnosis of Alzheimer’s disease.

The research collaboration—whose value was not disclosed—is designed to combine AC Immune’s lab capabilities and expertise in the biology and pathology of Tau with NIHS’ multiplexed antibody technology platform.

NIHS’ antibody technology was developed by its Prometheus Laboratories subsidiary, and is being applied by the institute in Brain Health research, specifically in Alzheimer’s. According to the institute, the assay uses an antibody microarray-based platform that measures the expression and activation of target proteins in tissues, blood, and other fluids.

The partners said they intend to identify and validate a highly sensitive diagnostic assay for detecting Tau in human cerebrospinal fluid and blood plasma.

“Our overarching goal is to develop nutritional approaches and technologies that help people maintain or re-establish their cognitive vigor,” Prof. Emmanuel E. (Ed) Baetge, Ph.D., director of NIHS, said in a statement. “This collaboration agreement opens up exciting new possibilities in the quest to better understand and combat this debilitating disease.”

Added Prof. Andrea Pfeifer, Ph.D., CEO of AC Immune: “Early diagnosis of this critical global health problem is equally needed for the development of pharmaceutical as well as nutritional approaches.”

Dr. Pfeifer also said the collaboration with NIHS marks AC Immune’s fourth partnership involving the Tau protein. The company’s three other partnered programs targeting Tau include the Phase Ib vaccine ACI-35, co-developed with Johnson & Johnson’s Janssen Pharmaceuticals; Tau PET tracers co-developed with Piramal as an Alzheimer’s diagnostic agent; and preclinical Tau-antibodies co-developed with Roche’s Genentech.

AC Immune focuses on designing, discovering, and developing therapeutic and diagnostic products designed to prevent and modify neurodegenerative diseases caused by misfolding proteins. Founded in 2003, AC Immune has raised CHF 84 million ($86.5 million) from private investors.

Wednesday, September 23, 2015

Scientists have built an inexpensive, portable sensor that enables fast and easy detection of multiple diagnostically relevant proteins. The diagnostically relevant protein (green or red), if present, binds to an electro-active DNA strand and limits the ability of this DNA to hybridize to its complementary strand located on the surface of a gold electrode. This causes a reduction of electrochemical signal, which can be easily measured with simple electronics. [Ryan & Peter Allen]

Does being able to test for allergies, STDs, or even cancer in minutes from the comfort and privacy of your home sound like science fiction? Well, a newly designed test from researchers at the University of Montreal could make it a reality before the next Star Trek movie comes to theaters.

The Canadian scientists have designed a rapid, inexpensive diagnostic test that should only take minutes to perform. This new design could aid efforts in building point-of-care devices for quick medical evaluations.

The tests are comprised of DNA molecules and the key to the new design is that it takes advantage of a basic force that drives molecular chemistry—steric effects, repulsion forces that arise when atoms are brought too close together. This design allows the assay to detect a wide range of protein markers associated with various disease states. 

"Despite the power of current diagnostic tests, a significant limitation is that they still require complex laboratory procedures. Patients typically must wait for days or even weeks to receive the results of their blood tests," explained senior author Alexis Vallée-Bélisle, Ph.D., professor in the department of chemistry at the University of Montreal. "The blood sample has to be transported to a centralized lab, its content analyzed by trained personnel, and the results sent back to the doctor's office. If we can move testing to the point of care, or even at home, it would eliminate the lag time between testing and treatment, which would enhance the effectiveness of medical interventions.”

The findings from this study were published recently in the Journal of the American Chemical Society through an article entitled “A highly selective electrochemical DNA-based sensor that employs steric hindrance effects to detect proteins directly in whole blood.”

Interestingly, a key breakthrough for the realization of the test design came about serendipitously. "While working on the first generation of these DNA-based tests, we realized that proteins, despite their small size (typically 1000 times smaller than a human hair) are big enough to run into each other and create a steric effect (or traffic) at the surface of a sensor, which drastically reduced the signal of our tests," said lead author Sahar Mashid, Ph.D.,  postdoctoral scholar at the University of Montreal "Instead of having to fight this basic repulsion effect, we instead decided to embrace this force and build a novel signaling mechanism, which detects steric effects when a protein marker binds to the DNA test."

The chemistry behind the sensing mechanism is fairly straightforward: a diagnostically relevant protein, if present, binds to an electro-active DNA strand, and limits the ability of this DNA to hybridize to its complementary strand located on the surface of a gold electrode. The resulting current created by the signaling mechanism is sufficient enough to be picked up by simple electronic devices, such as those used by in-home glucose meters.

Using this DNA-base assay, the investigators were able to detect multiple protein markers directly in whole blood in fewer than 10 minutes, even if their concentration was a million times less concentrated than glucose.

"A great advantage of this DNA-based electrochemical test is that its sensing principle can be generalized to many different targets, allowing us to build inexpensive devices that could detect dozens of disease markers in less than five minutes in the doctor's office or even at home," concluded Dr. Vallée-Bélisle.

Tuesday, September 22, 2015

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Human Longevity Inc. (HLI) will partner with Discovery to offer whole exome, whole genome, and cancer genome sequencing to the insurer's clients in South Africa and the U.K.

HLI will offer a full exome sequencing and analysis for Discovery's clients priced at $250. HLI will provide the information to Discovery, which will deliver reports to its clients through its network of physicians and genetic counselors. The reports will detail clients’ genome findings, including disease risk and potential wellness strategies.

The partners said Discovery clients will receive regular updates as new scientific discoveries emerge, and will be able to access updated reports via specially designed web and app interfaces. Discovery and HLI added that they will implement “the highest standards of data security” to ensure that client data is fully protected.

Through their agreement, HLI will also receive de-identified data from participating Discovery clients. The combined genomic and phenotypic data will become part of the HLI database and will support HLI in further expanding what it said was the world's largest and most comprehensive collection of whole genome, phenotype, and clinical data.

“The de-identified genomic data will be used for extensive ongoing research with numerous collaborators around the world, and we are excited that together with our clients, we will be able to make a material contribution to global research efforts aimed at improving the health of populations and reducing the growing burden of diseases of lifestyle,” Discovery Health CEO Jonathan Broomberg, M.D., Ph.D, said in a statement.

Discovery will offer the services and make them available through its Vitality Program, designed to promote behavioral wellness among its clients by giving them the tools, knowledge, access, and incentives to improve their health. The program is designed to encourage behavioral change, and enable behavior-linked insurance pricing.

Founded in 1992, Discovery serves more than 4.4 million clients across South Africa—the insurer is headquartered in Johannesburg—as well as the U.S., Australia, China, Singapore, and the U.K..

In the U.K., the Discovery-HLI partnership will be available to clients of VitalityHealth, whose holistic healthcare approach integrates wellness and prevention programs with traditional health coverage to more than 550,000 customers. VitalityHealth is a wholly-owned business within Discovery Group and was previously a joint venture with Prudential known as PruHealth.

Discovery and HLI said they will also develop and open HLI Health Nucleus centers in the U.K. as well as South Africa. HLI Health Nucleus is a free-standing health center designed to supply clients with a complete biological and health assessment of themselves through genome, microbiome, metabolome sequencing, along with comprehensive MRI body scans and traditional clinical testing.

The first Health Nucleus is opening next month at HLI's San Diego headquarters.

“We believe that genomic understanding of individuals is one of the best ways to positively impact human health and health outcomes. Together Discovery and HLI are paving the way for a new healthcare future," added J. Craig Venter, Ph.D., HLI co-founder and CEO.

Tuesday, September 22, 2015

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Working with tissue, blood, and DNA from six people with precancerous and cancerous lung lesions, scientists from Johns Hopkins scientists say they have identified what they believe are among the very earliest premalignant genetic changes that mark the potential onset of the most common and deadliest form of disease.

In a study (“Targeted sequencing reveals clonal genetic changes in the progression of early lung neoplasms and paired circulating DNA”) published online in Nature Communications, the team says the DNA alterations it uncovered were in premalignant lung lesions known as atypical adenomatous hyperplasia, or AAH, and that the alterations occurred long before the lesions would acquire the ability to invade surrounding tissue and fulfill the definition of adenocarcinoma of the lung.

"We believe we were able to detect, for the first time, DNA circulating in the blood from precancerous lesions of the lung," says Mariana Brait, Ph.D., an assistant professor of otolaryngology-head and neck surgery at the Johns Hopkins University School of Medicine and a member of the research team. "This work is a big step in advancing our knowledge of lung cancer because it could give us a chance to find people at risk early."

Their analysis also showed, they explain, that different regions of the same lesion had various mutations distinctly associated with good and poor outcomes, and that in patients for whom blood samples were available, circulating DNA evidence of the mutations showed up clearly.

"This study takes detection to a whole new level in terms of size of the lesion," says David Sidransky, M.D., professor of oncology and pathology at the Johns Hopkins University School of Medicine and the director of head and neck cancer research at Johns Hopkins. "I'm not aware that circulating DNA from precancerous lesions this small has ever been identified before."

He cautions that the findings are preliminary, involved only a few patients and are but a first step in figuring out how DNA testing might be used to detect precancerous changes at their earliest stages. But the knowledge is invaluable, he adds, for both understanding the molecular biology of how lung cancer originates and how to use the findings in clinical applications.

The prevailing opinion among lung cancer experts is that adenocarcinomas of the lung develop from microscopic lesions that accumulate multiple genetic alterations over time that then lead to malignancy. The problem is that many such precancerous lesions regress and disappear after a few years, but some will progress to cancer, says Evgeny Izumchenko, Ph.D., a postdoctoral fellow in Dr. Sidransky's laboratory and the lead author of the study.

To help sort out factors that might predict which small lesions progress to lung cancer, the team collected tissue samples from six patients undergoing surgical removal of lung tumors. Then William Westra, M.D., professor of pathology, went through the tissue samples millimeter by millimeter to single out tiny precancerous AAH lesions in the lung tissue for study.

The scientists then extracted and sequenced DNA from these AAH lesions, as well as from other adenocarcinomas in situ, minimally invasive adenocarcinomas and fully invasive adenocarcinomas, a spectrum of lesions that represent the progression from AAH to fully invasive adenocarcinoma.

Using a technique next-generation sequencing, they next looked for mutations in 125 genes known to play a significant role in cancer development and progression. By comparing the DNA of the premalignant lesions with DNA isolated from primary invasive cancer within each patient, the sequencing approach showed that in three of the patients, the same mutations were shared between the premalignant lesions and the tumor from the same patient. This is the first definitive link ever found between potential premalignant lesions and invasive tumors in the same lung, says Dr. Izumchenko, and it suggests that those mutations may be the drivers of tumor progression.

The team also found that different AAH lesions from different patients had unique patterns of mutations, indicating that lung cancer can be initiated by disturbances in different molecular pathways. The researchers also discovered, to their surprise, they report, that some of the lesions were dead ends, harboring mutations in their DNA that most likely were insufficient to progress to full-blown cancer.

When the team further explored different regions within the same lesion, they found genetic differences even within the same lesion. Mutations associated with good and poor prognosis or responses to therapy were seen in different regions of the same tumor, highlighting the limitations of single biopsies commonly used to decide patients' therapies, says Dr. Sidransky.

In another experiment using blood plasma and sputum from two patients, the researchers extracted DNA from these fluids and used digital polymerase chain reaction, an ultrasensitive method for detecting minute amounts of mutated DNA in a sample, to look for the same mutations they had found in each patient's biopsy samples. They detected those mutations in the fluids, even mutations found in only one specific zone of a lesion. Dr. Sidransky says that this finding may indicate that a blood or sputum test could better represent the overall composition of a tumor than a single biopsy sample.

Further studies are planned to confirm the findings in more lung cancer patients. "We have a glimpse into the future in which we can detect premalignant lesions in the lung before they become tumors," says Dr. Izumchenko. "But it is only the beginning of a long road we must travel to figure out how to interpret these discoveries to use them optimally in the clinic."

Monday, September 21, 2015

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Angelina Jolie’s experience undergoing preventive surgeries for breast and ovarian cancer after learning about her genetic predisposition may have spiked American’s awareness of cancer and genetics, but a new survey finds that additional engagement is sorely needed among patients, their families, and their clinicians.

The Genetic Risk Awareness Survey, conducted by Invitae in June 2015 among 1,000 Americans found that 73% of Americans are aware of genetic testing for hereditary cancers, a dramatic increase from less than 50% in 2010.

Although the “Angelina Jolie Effect,” has increased awareness of genetic testing, the study found that there is still confusion when it comes to how cancer is inherited. Americans also lack knowledge of their family healthy history and they have a strong desire for clinical guidance when pursuing genetic testing, according to the survey.

In fact, 80% of survey respondents said they would want their personal physician or a genetic counselor to provide access to genetic testing and advice on the results.

When queried if they are aware of news reports regarding Angelina Jolie’s decision to undergo surgery for cancer prevention, 76% of Americans surveyed said they were aware of her story and 47% respondents knew that her surgery was for breast cancer. Only 5% were aware that her surgery was for ovarian cancer.

Knowledge of BRCA1 and BRCA2 Genetic Mutations?

On the topic of familiarity with the BRCA1 and BRCA2 genetic mutations, which are linked to an increased risk of breast and ovarian cancer, only 32% of those surveyed said they were familiar with the BRCA genetic mutations that influenced Jolie’s decisions.

What’s more, some 47% of respondents are aware that these genetic mutations increase the risk of breast cancer, while only 3% said it indicates increased risk for ovarian cancer.

The majority of respondents, 64% are somewhat familiar with the use of genetic testing to identify a person’s increased risk of hereditary cancer, while only 9% are familiar, and 27% are not aware of genetic testing to identify risk at all.

Some 69% of respondents believe that a test that provides information on the risk of hereditary diseases would be helpful, 26% aren’t sure if a test would help them, and 5% said a test wouldn’t be helpful.

What steps have respondents taken based on their understanding of their risk of cancer or another disease? Lifestyle modifications were mentioned by 61% of respondents, 58% said they discussed the risk with healthcare providers, 56% reported they had medical testing and monitoring, 8% said they had an elective medical procedure, and 5% indicated they took other steps. 

The study also found the following:

• 43% of those surveyed said they did not know which hereditary diseases run in their family.
• Just 21% said they had a very accurate understanding of their family history.
• Almost half (48%) of those surveyed said they thought the combination of family history and genetic testing would be the most useful way to gauge hereditary cancer risk.

Ora Gordon, M.D., director of the Hereditary Cancer Prevention Program at the Disney Family Cancer Center of Providence St. Joseph Medical Center said, “We all know the importance of understanding and documenting our family history of disease, but for many people it’s a challenge. Tracking your family history and talking with your clinician about whether genetic testing is appropriate for you are important steps in assessing your risk of hereditary cancer.”

Tuesday, September 15, 2015

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MDx Health plans to acquire NovioGendix for up to $8.8 million, the companies said today, in a deal that expands the buyer’s uro-oncology offerings with a non-invasive urine-based molecular biomarker test for prostate cancer that is set to be launched to market next year in the U.S. and Europe.

Privately-held NovioGendix has focused on developing the “liquid biopsy,” an mRNA-based test designed to help differentiate patients with aggressive, clinically significant prostate cancer, from those with slower growing cancer. According to the company, initial comparative studies have shown the new mRNA test outperforms the prostate cancer antigen 3 (PCA3) gene test in clinical performance.

MDx Health CEO Jan Groen, Ph.D., said in a statement his company plans to launch the new test as SelectMDx for Prostate CancerTM in the US next year as a laboratory developed test. The test is CE-marked and validated to run on several PCR instruments, enabling MDx Health to enter the European and broader global urology markets with a kit option, the company said.

Dr. Groen said the NovioGendix facility in the Netherlands will allow MDx Health to expand its presence in Europe and will serve as a platform to launch the SelectMDxTM IVD kit in Europe, also in 2016.

"Our focus is to build MDxHealth into a market leader in molecular diagnostics for uro-oncology,” Dr. Groen stated. “The acquisition of NovioGendix provides us with a validated, non-invasive, actionable testing option for prostate cancer and allows us to address the larger market opportunity of initial prostate biopsy for early cancer detection, complementing our ConfirmMDx test for repeat biopsy."

MDxHealth said it will continue the scientific collaboration between NovioGendix and the Radboud University Medical Center in Nijmegen, the Netherlands, where the PCA3 test was discovered. In addition to SelectMDx, NovioGendix has a range of diagnostic tests for prostate, bladder, kidney and other urologic cancers in various stages of development.

NovioGendix was founded in 2007 by Jack A. Schalken, Ph.D., and Willem Melchers, Ph.D., and began operations the following year as a Radboud University Medical Center (Radboudumc) spinout company. Main shareholders of NovioGendix include fund manager BioGeneration Ventures, and Participatiemaatschappij Oost Nederland, a regional venture capital company that is part of East Netherlands Development Agency.

a regional venture capital company that is part of East Netherlands Development Agency - See more at: http://www.ppmoost.nl/page/ppm-oost-english#sthash.W7EVPrJ2.dpuf
a regional venture capital company that is part of East Netherlands Development Agency - See more at: http://www.ppmoost.nl/page/ppm-oost-english#sthash.W7EVPrJ2.dpuf

MDx Health said it will propose appointing Dr. Schalken to its board as an independent director following the completion of the deal, which is expected to occur on or about September 18.

MDxHealth agreed to purchase all outstanding shares of NovioGendix Holding for up to $8.8 million in cash and stock. Of the purchase price, $5.1 million is payable in new MDxHealth shares, $283,345 in cash—and up to an additional $3.3 million cash is tied to achieving unspecified milestones. MDxHealth also agreed to grant NovioGendix a bridge loan of $680,000 to repay outstanding debts.

MDxHealth said it anticipates the acquisition will add approximately $0.5 million in 2015 operating expenses, excluding acquisition-related expenses.

Friday, September 11, 2015

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True Health Diagnostics agreed to pay $37.1 million to acquire Health Diagnostic Laboratory (HDL) after emerging as the successful bidder at a U.S. Bankruptcy Court auction, HDL said today.

The sale is subject to final approval by Judge Kevin R. Huennekens of the U.S. Bankruptcy Court for the Eastern District of Virginia. He has set a Sept. 16 hearing on the matter.

Headquartered in Frisco, TX, privately-held True Health specializes in advanced clinical laboratory testing intended to help healthcare providers more accurately diagnose, manage, and prevent the progression of cardiovascular diseases, genetic disorders, diabetes, and other metabolic conditions.

“HDL’s culture of innovation and scientific excellence and commitment to compliance with healthcare regulatory requirements aligns perfectly with ours,” True Health CEO Chris Grottenthaler said in a statement. “Together, we will have the scale and talent we need to pursue new market opportunities.

“While HDL, Inc. has encountered financial challenges, I have no doubt its best days are ahead,” Grottenthaler added. “The acquisition by True Health is the best possible outcome for all involved, including employees from both companies, the Richmond community, healthcare providers and their patients.”

Founded in 2008, HDL provides comprehensive biomarker testing and clinical health consulting for earlier disease detection and targeted disease management. In addition to lab testing, HDL offers patients personalized overviews of their lab results and counseling intended to promote healthier lifestyles.

In June, HDL filed for protection from creditors under Chapter 11 of the U.S. Bankruptcy Code. According to a court filing, HDL’s largest unsecured creditor is the U.S. Justice Department, which is owed $49.5 million after the company agreed in April to settle federal allegations that it violated the False Claims Act by paying physicians in exchange for patient referrals and billing federal health care programs for medically unnecessary testing.

HDL had named True Health as the auction’s “stalking horse” bidder on September 4. True Health’s initial $32 million bid rose during the bidding process by more than $5 million, as multiple bids were submitted during yesterday’s auction, held at the Richmond, VA, office of HDL’s restructuring counsel Hunton & Williams.

The transaction is expected to be completed by the end of the month, HDL said.

“HDL, Inc. is pleased that our cutting edge diagnostic testing will continue to be utilized in the vitally important and continuing battle to fight cardiovascular disease and diabetes,” HDL President and CEO Joseph McConnell said in a statement. 

Wednesday, September 09, 2015

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Asuragen agreed to collaborate with Illumina to set up a framework for the development and commercialization of sequencing-based companion diagnostics in partnership with biotech and pharmaceutical companies. Asuragen  officials say they will leverage its Quantidex™ NGS product platform for development of customized companion diagnostics for its biotech and pharma partners on the Illumina MiSeqDx™ instrument

Asuragen’s recently launched Quantidex™ Pan Cancer [research] Kit demonstrates its optimized NGS system that unifies pre-analytical DNA QC, sample quantification, multiplex PCR enrichment, dual-index barcoding, and library purification and quantification, using reagents provided in a single kit, according to Matt McManus, president and CEO of Asuragen.. “It integrates Asuragen’s analytics and reporting suite, the Quantidex™ Reporter, providing a straight forward sample-to-answer solution for Asuragen NGS panels,” he added.

Tuesday, September 08, 2015

Big data scientists have developed a new online tool to better understand the immune system's role in combating disease. [Dmitry Zaslavsky and Stuart Sealfon]

Analyzing and compiling large datasets is one of the fundamental principles behind the development of computational systems that evolved into modern computers. But what happens when the datasets become so large or complex that traditional processing applications are inadequate? Such are the questions presented to Big Data scientists who are trying to disseminate the seemingly insurmountable glut of digital information.

Nowhere has the big data push had a bigger impact than on the field of genomics. Understanding the key interactions between genes contained within the human genome and the subsequent proteins for which they code is critical to unlocking the functional roles of specific biomolecules in disease states.

In order to address many of these genomic issues researchers from the Icahn School of Medicine at Mount Sinai and Princeton University have designed a new online tool that predicts the role of key proteins and genes in diseases of the human immune system. 

“The resulting comprehensive web-accessible resource (ImmuNet) facilitates researchers’ use of the global data output to generate testable hypotheses for specific immunological research areas,” noted the scientists. “We demonstrate the value and ease of use of ImmuNet to complement genetic studies for identifying disease-associated genes.”

The online tool uses information compiled from 38,088 public experiments in order to predict new immune pathway interactions, mechanisms, and disease-associated genes. Due to advances in computing power and storage, combined with sharp declines in technology prices, big data researchers are able to combine more powerful algorithms and models into tools such as ImmunNet—which can pull previously unidentified disease patterns from databases. 

"This new tool unlocks the insight contained in big data, the world's biomedical research output, to help understand immunological mechanisms and diseases," explained co-senior author Stuart Sealfon, M.D., professor and chairman of the department of neurology at Mount Sinai Health System. "The goal of 'ImmuNet' is to accelerate the understanding of immune pathways and genes, ultimately leading to the development of improved treatment for diseases with an immunological component."

The findings from this study were published online late today in Immunity through an article entitled “Interactive Big Data Resource to Elucidate Human Immune Pathways and Diseases.”

ImmuNet enables immunology researchers without special computational training to use the statistical techniques of Bayesian data integration—an interpretation of statistical probability—and machine learning algorithms to "interrogate" this huge archive of public data. Analyses such as these are able to detect relevant information among the sea of often-conflicting data obtained from diverse experiments. Additionally, Bayesian analysis is able to discern only those datasets that provide new insight about a pathway of interest while excluding datasets that are not relevant to the targeted pathway.

The researchers stressed that one of the main goals of ImmuNet is to advance the understanding of the immune system, the network of cells and organs that protects the body against infections and cancer.

"We expect the applicability of ImmuNet to wide-ranging areas of immunology will grow with the incorporation of continually increasing public big data," stated co-senior author Olga Troyanskaya, Ph.D., professor in the department of computer science and Lewis-Sigler Institute of Integrative Genomics at Princeton University. "By enabling immune researchers from diverse backgrounds to leverage these valuable and heterogeneous data collections, ImmuNet has the potential to accelerate discovery in immunology."

Tuesday, September 08, 2015

Source: iStock/© agsandrew

AstraZeneca and The University of Manchester today said they would partner to deliver personalized healthcare for cancer patients through the use of clinical bioinformatics.

Under their five-year agreement, the company and the university said they will apply clinical trial bioinformatics with the aim of better identifying cancer treatments for individual patients.

AstraZeneca has agreed to provide a total of £11.5 million ($17.7 million) to support clinical bioinformatics research led by a team of investigators within the recently established Centre for Cancer Biomarker Sciences at the Manchester Cancer Research Centre. The research will be carried out in partnership with the clinical trials unit of The Christie National Health Service (NHS) Foundation Trust, which focuses on experimental cancer medicine in the U.K.

Projects by the partners will include the development of a new bioinformatics system to capture and integrate clinical trial safety, efficacy, biomarker and drug distribution data in real time, presenting the information in the form of graphs that can be easily interpreted by clinicians.

The collaboration will also support new training programs in clinical research and pharmacokinetic and pharmacodynamic modeling for investigators to understand the distribution and clinical effects of medicines within the body, AstraZeneca and the university said.

“This collaboration is exciting because it will eventually allow us to incorporate important data from clinical trials into a format that can be reviewed in real time by healthcare professionals and matched with information about cancer medicines,” Mene Pangalos, evp, innovative medicines & early development with AstraZeneca, said in a statement. “We will be able to modify clinical trial programs accordingly and support clinicians to offer more accurate, personalized and rapid decision making to patients about their treatment.”

The collaboration is the latest between AstraZeneca and the university, and builds on scientific collaborations launched in recent years by AstraZeneca and The University of Manchester. The earlier collaborations range from research into novel cancer medicines to progressing treatments for lung cancer, advancing inflammatory research, and developing new drug delivery systems.

“AstraZeneca has long supported the UK science base and this latest collaboration with the Manchester Cancer Research Centre will enable the patients to share their insights with investigators and sponsors more effectively and efficiently than today, enabling a more informed assessment,” added Andrew Hughes, Ph.D., professor of experimental cancer medicine at the university’s Institute of Cancer Sciences.

Tuesday, September 01, 2015

Source: iStock/izusek

Inequality. The word had all but vanished from public discussion of economic policy. Then Occupy Wall Street happened, and suddenly “inequality” was on everyone’s lips, as though people were waiting for an opportunity to recognize, however belatedly, an uncomfortable truth—individual virtue doesn’t guarantee security, let alone prosperity. And, finally, people felt free to admit that there might be, after all, such a thing as society.

A comparable shift in discourse may be in store for precision medicine, if two public health scholars have anything to say about it. These scholars—Sandro Galea, M.D., Dr.P.H., and Ronald Bayer, Ph.D.—are adamant that differences in public health outcomes are less a matter of access to medical care than they are a matter of sheer socioeconomic differences. Moreover, they suggest that if access to medical care matters relatively little, the availability of precision medicine matters even less.

For the rest of the story, click here.

Tuesday, September 01, 2015

Source: iStock/© evryka23

The genetic basis of a patient’s cancer is often unclear. A patient’s cancer may be driven by just one out of many possible genetic causes, or it may be the culmination of multiple genetic causes. All of these possibilities exist in a kind of cloud, which is complemented by another sort of cloud, which consists of the various cancer-suppression activities that one drug, or a combination of drugs, may have. Some drugs are “promiscuous.” For example, some cancer drugs inhibit multiple cancer-related kinases.

A patient’s cancer-driver cloud might overlap with a particular drug’s cancer-suppression cloud, but who could say? We’re dealing with clouds, after all, not the crisply bound regions we see in Venn diagrams.

For the rest of the story, click here.

Tuesday, September 01, 2015

A genomic marker panel was recently described that has the ability to predict tumor aggressiveness in a race-dependent manner. [iStock/gchutka]

GenomeDx Biosciences reported that its commercially available Decipher® testing platform identified, with statistical significance, a set of prostate cancer biomarkers predictive of aggressive disease in African American men after radical prostate surgery. This represents the first and only study describing a set of genomic markers that have the ability to predict tumor aggressiveness in a race-dependent manner, said Elai Davicioni, Ph.D., president and CSO at GenomeDx and an author on a study (“Novel Biomarker Signature That May Predict Aggressive Disease in African American Men With Prostate Cancer”), that was published online in the Journal of Clinical Oncology.

Additionally, the study demonstrated that the Medicare-covered Decipher test is an independent predictor of metastasis in African American men.

For the rest of the story, click here.

Tuesday, September 01, 2015

The primary goal of the Paradigm Registry is to accelerate tumor profiling based on disease biology. [iStock/LilliDay]

Paradigm and TME Research launched the Paradigm Neoadjuvant Breast Registry. The system will use Paradigm’s PCDx next-generation sequencing test and other advanced molecular capabilities to genomically characterize invasive breast cancer patients for targeted neoadjuvant therapies [presurgical treatment]. With more accurate accounts of individual gene variability driving disease, therapy selection will be refined for patient success, according to officials at Paradigm.

The initial six-month pilot for this project will enroll 100 patients across eight primary U.S. centers, potentially expanding to 1,000 patients across 50 U.S. centers. Patients enrolled into the Paradigm Registry will have neoadjuvant chemotherapy or hormone therapy. The patient’s cancer will undergo tumor profiling with the Paradigm platform. 

Precision oncology is an emerging approach for cancer treatment utilized mainly in the metastatic setting but with great potential to direct initial therapy, said Robert J. Penny M.D., Ph.D., CEO of Paradigm. The primary goal of the Paradigm Registry is to accelerate tumor profiling based on disease biology so that relevant neoadjuvant clinical trials and/or refined treatment regimens can be identified particularly when competing options exist.

For the rest of the story, click here.

DeeAnn Visk, Ph.D.

Tuesday, September 01, 2015

Definiens, a provider of image analysis and data-mining solutions for tissue diagnostics, generated this image to represent the company’s technological approach: providing detailed cell-by-cell readouts from target structures on tissue slides, and correlating this information with data derived from other sources. This approach is meant to generate new knowledge and support better decisions in research, diagnostics, and therapy.

Molecular pathology attempts to describe and understand the origins and mechanisms of disease by evaluating the molecular content of patient samples. Increasingly, “molecular content” is being seen as an intricate, interconnected whole, a dynamic collection of interacting parts. In other words, context is all.

Context was a recurring theme at the Pathology Diagnostics Conference, a key piece of the Molecular Diagnostics Summit recently held in San Diego. At this event, several presenters emphasized the ways pathology results may become more meaningful if, for example, morphological and spatial information is preserved in molecular tests, or—more generally—imaging is integrated with data analysis.

Presenters also indicated that mining molecular pathology not only yields clinical paydirt, it also conserves scarce healthcare resources. For example, Bonnie Anderson, President and CEO of Veracyte, asked how molecular pathology could be used to impact the healthcare system and reduce costs: “Where can we impact the healthcare system to reduce cost? How can efficiency be increased by using genomic technology?” Patients, Anderson noted, often endure multiple procedures in expensive diagnostic odysseys.

For the rest of the story, click here.

Jeffrey S. Buguliskis, Ph.D.

Tuesday, September 01, 2015

NGS technology has enabled researchers to epidemiologically analyze DNA sequences by quickly deciphering mass quantities of genetic information in a short amount of time. [Heart illustration: iStock/SvetaP DNA double helix: iStock/Kagenmi]

Since cardiovascular disease (CVD) still represents the leading cause of death in the United States, researchers are, if anything, only more determined to identify the triggers of disease and those who may be at greatest risk. Science has made considerable progress over the years identifying and even treating many of the risk factors that contribute considerably to CVD progression (e.g., hypertension, type 2 diabetes, cigarettes, and physical inactivity), resulting in an overall decline in mortality rates.

However, in the genomic age, researchers feel they can push the diagnostic testing boundaries even further by testing for subclinical disease through specific genetic biomarkers. This spirit animates a recent report published online ahead of print in Nature and discussed in GEN. It describes how a scientific team led by researchers at Massachusetts General Hospital discovered the first gene linked to mitral valve prolapse (MVP).

While it has been well documented that MVP is heritable and variably expressed in families, a specific genetic marker had not been previously identified. Although more work will need to be done with larger cohorts of MVP patients to determine the prevalence of the mutation in the DCHS1 gene, the identification of this genetic mechanism may hold potential for presurgical therapeutic intervention—an important discovery given that MVP affect nearly 1 in 40 people worldwide. 

For the rest of the story, click here.

Tuesday, September 01, 2015

The September issue of Clinical OMICs is available now! Check it out by clicking on the link below.

Clinical OMICs Volume 2, Issue No. 9

Renee Deehan Kenney

Tuesday, September 01, 2015

Source: iStock/ttsz

With the emergence of a wide array of new therapies for the management of rheumatoid arthritis, not only has treatment improved markedly over the past two decades, it has also grown increasingly complex. With 10 approved biologic therapies in the United States comes a growing need for tools that can turn complex biological data into actionable insights for physicians and patients to make informed and personalized treatment decisions.

A progressive and debilitating autoimmune disease, rheumatoid arthritis (RA) causes pain and stiffness and over time leads to joint damage and disability. It occurs when a person’s immune system goes awry, causing inflammation in healthy joints. About 2.4 million people in the United States have RA; of those, more than 1 million have moderate to severe disease.

For the rest of the story, click here.

Patricia Fitzpatrick Dimond, Ph.D.

Tuesday, September 01, 2015

Healthcare professionals express concern that due to complexities of genetic testing and counseling, the self-ordering of genetic tests by patients could cause harm. [DepositPhotos/ Julia_Tim (modified by Clinical OMICs]

The NIH defines direct-to-consumer genetic tests (DTCs) as those aimed at consumers via television, print advertisements, or the Internet. Also known as at-home genetic tests they provide access to a person’s genetic information without necessarily involving a doctor or insurance company in the process.

Causing controversy among healthcare professionals and heavily marketed by the companies that provide them, the tests prompted concern among healthcare professionals, such as the American College of Medicine Genetics board of directors, which said in 2004 that due to complexities of genetic testing and counseling, the self-ordering of genetic tests by patients could potentially cause harm. Potential pitfalls, according to the organization, include inappropriate test utilization, misinterpretation of test results, lack of necessary follow-up, and other adverse consequences.

The widespread availability of these tests offered by multiple companies, including 23and Me, Decode Genetics, DNA Direct, and Genelux to name a few, had driven consumer demand and interest.

For the rest of the story, click here.

Monday, August 31, 2015

Source: iStock/Yuri_Arcurs

Merck & Co. will partner with Daktari Diagnostics to develop Daktari’s rapid hepatitis C virus (HCV) screening test, under a collaboration that will generate up to $8.5 million over three years for the diagnostics developer.

The collaboration is designed to support an accelerated development timeline for the clinical validation and regulatory approval of the HCV test, according to Daktari, which announced the deal today.

Daktari’s technology will form the basis of a point-of-care instrument intended to detect low levels of virus directly in a single drop of blood in approximately 30 minutes, making on-the-spot HCV treatment decisions possible.

The Daktari test is based on high-sensitivity measurement of the HCV core antigen, which is used in Europe and Japan for the diagnosis of chronic hepatitis C infection, but has never been available as a point-of-care diagnostic.

The Daktari™ System includes an embedded connectivity platform, Daktari InSight, designed to provide real-time data management through mobile network connectivity and a web-based dashboard, allowing rapid monitoring of test results.

According to Daktari, the system could be made available at retail clinics, pharmacies, and doctor's offices.

“Merck's collaboration provides support for an accelerated development and regulatory timeline for our HCV diagnostic,” Bill Rodriguez, M.D., Daktari’s founder and CEO, said in a statement.

The collaboration extends Merck’s involvement in Daktari. Merck’s Global Health Innovation (Merck GHI) fund led Daktari’s $10 million staged financing round completed in 2011; co-led a $13 million series C round that closed in 2014; and co-led the diagnostics developer’s $15.5 million series D financing round, closed in March.

In addition to hepatitis C, HIV, and other infectious diseases, Daktari said, it is also developing cardiology and hematology tests for use in doctor's offices and emergency rooms.

Thursday, August 27, 2015

Women who tested positive for circulating tumor DNA were at 12 times the risk of relapse of those who tested negative. Relapses could be predicted about 8 months before they became clinically apparent. [© prudkov/Fotolia]

Conducted repeatedly, a blood test capable of profiling circulating tumor DNA can track genetic changes that occur over time, picking up signs that a treated cancer—in this case, breast cancer—is about to return. The blood test, a so-called liquid biopsy, detects mutations in DNA shed by cancer cells, and it can be used to predict breast cancer relapse about 8 months before tumors become visible on hospital scans.

A liquid biopsy not only spares patients the invasive procedures needed to collect solid tumor samples, it can be repeated easily, catching key mutations that cancer accumulates as it develops and spreads. To create a liquid biopsy for breast cancer, scientists at the Institute of Cancer Research in London, developed a polymerase chain reaction (PCR) test that is sensitive to the sorts of mutations common to many types of breast cancer.

The researchers described their test August 26 in the journal Science Translational Medicine, in an article entitled, “Mutation tracking in circulating tumor DNA (ctDNA) predicts relapse in early breast cancer.” The article detailed the analysis of circulating tumor DNA in plasma, and showed how it may be used to enable monitoring for minimal residual disease (MRD) in breast cancer.

“In a prospective cohort of 55 early breast cancer patients receiving neoadjuvant chemotherapy, detection of ctDNA in plasma after completion of apparently curative treatment—either at a single postsurgical time point or with serial follow-up plasma samples—predicted metastatic relapse with high accuracy,” wrote the authors. “Mutation tracking in serial samples increased sensitivity for the prediction of relapse, with a median lead time of 7.9 months over clinical relapse.”

The authors added that analysis of ctDNA could define the genetic events of MRD, and that MRD sequencing predicted the genetic events of the subsequent metastatic relapse more accurately than sequencing of the primary cancer. They also pointed out that their test could identify the particular mutations likely to prove lethal to individual patients, raising the possibility of tailored treatments.

“We have shown how a simple blood test has the potential to accurately predict which patients will relapse from breast cancer, much earlier than we can currently,” said study leader Nicholas Turner, Ph.D., team leader in molecular oncology at the Institute of Cancer Research. “We also used blood tests to build a picture of how the cancer was evolving over time, and this information could be invaluable to help doctors select the correct drugs to treat the cancer.

"Ours in the first study to show that these blood tests could be used to predict relapse. It will be some years before the test could potentially be available in hospitals, but we hope to bring this date closer by conducting much larger clinical trials starting next year."

“We are moving into an era of personalized medicine for cancer patients,” added Paul Workman, Ph.D., chief executive of the Institute of Cancer Research. “This test could help us stay a step ahead of cancer by monitoring the way it is changing and picking treatments that exploit the weakness of the particular tumor. It is really fantastic that we can get such a comprehensive insight about what is going on in the cancer all over the body, without the need for invasive biopsies.”

Wednesday, August 26, 2015

8 in 10 patients with acute myeloid leukemia relapse after remission, and for most of them there's no reliable way to predict relapse. But new research suggests that performing genetic profiling while a patient is in remission can help physicians assess response to treatment and determine whether aggressive, follow-up treatment is necessary. [Darryl Leja, NHGRI]

While the incidence of acute myeloid leukemia (AML) is still relatively rare, accounting for approximately 1% of cancer deaths in the U.S., rates of occurrence are expected to rise as the largest portion of the population continues to age. Moreover, there remains a significant level of disparity in clinical outcomes, as 50% of patients relapse and die from refractory disease after an initial response to chemotherapy.  

Now, researchers from the Washington University School of Medicine (WUSM) have published data that suggests lingering cancer-related mutations—detected after initial treatments—are associated with an increased risk of relapse and poor survival.

The investigators used next-generation sequencing techniques to profile bone marrow samples from patients with AML. They found that cells carrying mutations 30 days after the initial chemotherapy treatment were roughly three times more likely to relapse and die than patients who cleared the mutations.   

"Most patients diagnosed with AML fall into a gray area when it comes to being able to predict their risk of relapse," explained senior author Timothy Ley, M.D., professor of oncology in the Department of Medicine at WUSM. "About 80 percent of AML patients go into remission with chemotherapy, but most of them eventually will relapse. Unfortunately, we still don't have a definitive test that tells us early on which patients will relapse.”

Dr. Ley continued, stating that "such information is important to know because high-risk patients need aggressive, potentially curative therapy with a stem-cell transplant when they are in remission, early in the course of the disease. However, we don't want to transplant patients who are unlikely to relapse following conventional chemotherapy because the transplant procedure is expensive and carries a significant risk of severe side effects and even death."

The findings from this study were published recently in JAMA through an article entitled “Association Between Mutation Clearance After Induction Therapy and Outcomes in Acute Myeloid Leukemia.”

The WUSM scientists utilized whole genome and exome sequencing on bone marrow samples obtained from 50 patients at the time of their diagnosis and 30 days after the initiation of chemotherapy. The researchers found that 24 of the patients had persistent mutations within their bone marrow cells—suggesting that at least some of the leukemia cells had survived the initial therapy. Additionally, in several cases these same cells were shown to expand and contribute to relapse.  

Those with persistent mutations had a median survival of only 10.5 months, compared with 42 months for the 26 patients whose leukemia mutations had been cleared by initial chemotherapy.

“If our results are confirmed in larger, prospective studies, genetic profiling after initial chemotherapy could help oncologists predict prognosis early in the course of a patient's leukemia and determine whether that patient has responded to the chemotherapy—without having to wait for the cancer to recur," stated lead author Jeffery Klco, M.D,. Ph.D., assistant faculty member at St.Jude Children's Research Hospital. "This approach to genetic profiling, which focuses on performing genome sequencing after a patient's initial treatment, also may be useful for other cancers."

The researchers are now looking into developing assays to detect residual disease after AML treatment, as well as formulating new therapeutic regimens to target the residual disease.

"These findings build on studies performed more than a decade ago that suggested the failure to clear leukemia cells bearing chromosomal abnormalities was associated with increased risk of relapse,” said Dr. Ley. “But that technology was applicable only for the subset of patients with abnormal chromosomes, while genome sequencing can detect mutations in virtually all patients and is much more sensitive and specific. This new approach gives us a way to think about how to use genomics to evaluate the risk of relapse for nearly all AML patients."

Wednesday, August 26, 2015

Source: © Photographee.eu/Fotolia.com

Sequenom agreed to a clinical research collaboration with the University of California, San Diego Moores Cancer Center. Moores will explore the utility of Sequenom's new liquid biopsy assay to profile circulating cell-free tumor DNA in blood to enable serial monitoring and assist with therapy selection in cancer patients. This technology has the potential to overcome the challenges and limitations associated with current methods such as imaging and invasive biopsies, according to Razelle Kurzrock, M.D., chief of the division of hematology & oncology and Murray Professor of Medicine, senior deputy director of clinical science and director of the center for personalized cancer therapy & clinical trials office..

"Sequenom has designed a comprehensive multi-gene panel based on the clinical actionability of cancer genes. The ability to match patients to a growing list of treatments and to monitor their response by a simple blood draw promises to make a significant difference in the way we treat cancer patients at UC San Diego," said Dr. Kurzrock. "The collaboration with Sequenom will allow us to analyze more cancer-related genes in the blood than previously possible to better understand tumor heterogeneity and the emergence of resistance mutations."

Sequenom is currently developing a research use only (RUO) assay with an initial focus on the detection and molecular profiling of late stage non-hematologic malignancies, where tissue biopsies are not available or too risky to obtain. A Sequenon official point out that the assay will cover a breadth of cancer types by analyzing over 100 cancer-related genes that are associated with a FDA-approved drug treatment, included in professional society guidelines, linked to targeted therapies currently in clinical trials, or part of well-documented cancer pathways. 

Tuesday, August 25, 2015

iStock/© baona

Illumina and Burning Rock said today they will collaborate to develop new clinical molecular diagnostics aimed at cancer. The value of the partnership was not disclosed.

Under the collaboration, Burning Rock will develop advanced clinical applications for molecular diagnostics in oncology based on Illumina's next-generation sequencing (NGS) technology. Specifically, the companies said they will work together to develop a user-friendly, oncology molecular diagnostic kit for the Chinese market.

Burning Rock agreed to provide its nucleic acid extraction, library preparation, and data analysis software, while Illumina agreed to provide NGS instrument components and related reagents, the companies said.

The deal reflects Illumina’s increased focus in recent quarters on both clinical uses for its technologies, as well as expansion in China.

On the company’s quarterly earnings conference call July 21, Illumina CEO Jay Flatley told analysts: “We haven't seen any real changes in the Chinese market over the last couple of quarters,” despite the country’s economic slowdown, according to a transcript published by Seeking Alpha—though he added: “The research funding was better in the Chinese market, maybe, 18 months ago than it has been over the past year.”

“Cooperation between our two companies will provide additional high-quality molecular diagnostic solutions in the clinical field of oncology," Yusheng Han, founder and CEO of Burning Rock, said in a statement. “Oncology molecular diagnosis based on NGS, including non-invasive testing, is being applied in the clinic and we hope to promote it as a standard practice in hospitals.”

Headquartered in Guangzhou, China, Burning Rock offers research and commercialized clinical laboratory services mainly through bioinformatics on NGS platforms. The company’s molecular and pathological examination platform includes NGS as well as qPCR, IHC, FISH and digital pathology technologies.

Thursday, August 20, 2015

Researchers announced results from the first published basket study, a new form of clinical trial design that explores responses to drugs based on the specific mutations in patients’ tumors rather than where their cancer originated.[iStock/ Vic2473]

One of the main goals of personalized medicine is the ablity to quickly and accurately determine the genetic background of a patient and prescribe the appropriate therapy based on their mutational signature. To address this vital component of modern medicine initiatives, researchers have designed a new form of clinical trial, dubbed a basket study, which explores responses to drugs based on the specific mutations in patients’ tumors rather than where their cancer originated.

Now, clinical researchers from Memorial Sloan Kettering Cancer Center (MSK) have published results from an early Phase II study that looked at the effect of the drug vemurafenib in multiple nonmelanoma BRAF V600-mutated cancers from a 122 patients in 23 centers around the world. Vemurafenib has been shown previously to be effective at treating BRAF V600-mutated melanoma, but this is the first report of the compound being used to treat nonmelanoma cancers such as lung, colorectal, and ovarian.  

“This study is the first deliverable of precision medicine. We have proven that histology-independent, biomarker-selected basket studies are feasible and can serve as a tool for developing molecularly targeted cancer therapy,” explained senior study author José Baselga, M.D., Ph.D., Physician-in-Chief and Chief Medical Officer at MSK. “While we can—and should—be cautiously optimistic, this is what the future of precision medicine looks like.”

The findings from this study were published recently in the New England Journal of Medicine through an article entitled “Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations.”

Basket studies allow for the detection multiple tumor types simultaneously, while permitting for the possibility that a specific tumor lineage might influence drug sensitivity. The current study is the first to follow this model and aims to explore treatment responses among tumors based on their mutation types and to identify promising signals of activity in individual tumor types that could be pursued in subsequent studies. Ultimately, the results should guide researchers to look at different drug targets or develop new combination therapies that combine with vemurafenib with complementary treatments.

In this study the investigators found that of the 122 participants, clinical activity was observed in a variety of tumor types such as non-small cell lung cancer, Erdheim-Chester disease, and Langherhans cell histiocytosis. Response rate and median progression-free survival in non-small cell lung cancer was 42% and 7.3 months, respectively. In Erdheim-Chester disease and Langherhans cell histiocytosis, the response rate was 43%—despite median treatment duration of 5.9 months, no patients progressed during therapy.

“This kind of study is a beneficial way to do rare tumor research because it allows us to open the study to patients with diseases that are completely underrepresented in clinical trials, in general, such as anaplastic thyroid cancer and glioblastoma,” stated David Hyman, M.D., the study’s lead author and acting director of developmental therapeutics at MSK. “By broadening eligibility, we are translating potential benefits to as large a patient population as possible.”

The authors were excited by their findings and noted that this study was the first part of an imminent flood of such studies focused on cancer-related mutations identified through the huge amounts of genomic data generated over the past several years.

“We now have the landscape of all the most frequent cancer-causing mutations in the majority of tumor types, and we know there are a number of genes that are frequently mutated in some tumors and less frequently in others,” Dr. Baselga noted. “The next step is exploring appropriate drug combinations, knowing that these cells have a finite number of pathways.”

Tuesday, August 18, 2015

Source: iStock/© Svisio

Illumina, Warburg Pincus, and Sutter Hill Ventures set up a company with the goal of helping consumers discover insights into their own genomes. The new firm, Helix, is based in the San Francisco Bay Area and reported received financing commitments in excess of $100 million.

“Genomics is reaching an inflection point in cost, volumes, and knowledge, creating a significant opportunity to unlock information that is currently not widely accessible to individuals,” said Jay Flatley, CEO of Illumina and chairman of the board of Helix.

Helix will enable individuals to acquire an unprecedented amount of genetic information by providing affordable sequencing and database services for consumer samples brought through third party partners, driving the creation of an ecosystem of consumer applications, explained Flatley. “After being sequenced, individuals will be able to manage their data and explore an open marketplace of on-demand applications, provided by Helix’s partners, to gain additional insights into the genomic data that has already been acquired. By converting genetic information to digital data stored in the cloud, Helix enables its partners to develop and deliver premium genomic products to consumers without the burden of developing their own assay, laboratory, or database infrastructure.”

Helix already has formed a partnership with the Center for Individualized Medicine at the Mayo Clinic. The Center is collaborating with Helix to develop applications initially focused on consumer education and health-related queries. The Mayo Clinic also made a strategic investment in Helix. Helix also found a second partner in the Laboratory Corporation of America, which will develop and offer analysis and interpretation services, initially focused on medically actionable genetic conditions, to consumers through Helix’s platform. Helix expects that other partners will develop applications focused on areas such as genealogy, fitness or wellness, and inherited traits to enable insights related to an individual’s genetics.

According to Flatley, Helix will establish one of the world’s largest next-generation sequencing labs and a secure and protected database, all designed in accordance with CLIA, CAP, and HIPAA guidelines. The aim is to allow Individuals to control how their data is accessed.

Tuesday, August 18, 2015

Source: © iceteastock/Fotolia.com

Biogen, the ALS Association, and Columbia University Medical Center (CUMC) agreed to collaborate to better understand the differences and commonalities in the ALS disease process and how genes influence the clinical features of the disease. The project, “Genomic Translation for ALS Clinical care” (GTAC), will involve a combination of next-generation sequencing and detailed clinical phenotyping in 1,500 people with ALS.

The goal of the project is to provide a basis for the development of precision medicine, or more individually tailored therapies for ALS.

“We want to bring genomics right to the point of care in ALS where instead of focusing on retrospective DNA samples with limited clinical information, we focus on patients who are under active clinical management,” said Lucie Bruijn, Ph.D., chief scientist at the ALS Association. “By focusing on patients seen by participating ALS clinics, this project will allow investigators to ask how different genetic causes of ALS translate into different clinical consequences.”

An explicit aim of the collaboration is to set the stage for a nationwide effort to ensure the genomic characterization of all patients with ALS.

“We know that ALS is not just one disease,” explained Tim Harris, svp, precision medicine at Biogen. “This study will help in developing a detailed understanding of how different genes contribute to different clinical forms of ALS. This will in turn help us design better, more focused clinical trials for the development of more effective treatments. This kind of ‘precision medicine,’ in which a treatment is tailored to a person’s unique genetic make-up, is already being used in the cancer field. It is an approach we feel is ready for ALS too.”

“Until recently, most large-scale genomics studies used archived DNA samples, so the findings had minimal impact on patient care,” added David B. Goldstein, Ph.D., professor of genetics and development and director of the Institute for Genomic Medicine at CUMC. "This project reflects our commitment to using ALS genomic studies to benefit patients directly through diagnoses and to set the stage for genetically stratified clinical trials.”

“This project will provide a clinical deliverable to the 1,500 patients that participate in the study. We will use our extensive database of ALS genomes and exomes to carefully identify definitive genetic risk factors for ALS and these risk factors will be communicated back to participating clinics. The database we create will allow for an unprecedented investigation of the clinical correlates of the genetic causes of ALS,” added Matthew Harms, M.D., who will lead the project and be joining CUMC in the fall as an assistant professor of neurology.

Patient blood cells will be stored at the Induced Pluripotent Stem Cell (iPSC) Core, a facility supported by the ALS Association, at the Cedars-Sinai Board of Governors Regenerative Medicine Institute. This cell bank will allow researchers to create cell lines for further study, based on leads provided by genome sequencing.

“The ability to create patient iPS cells from such a genetically well-annotated ALS blood repository will allow us to model causes of motor neuron degeneration in ALS at a scale that has never been possible,” said Dhruv Sareen, Ph.D., who leads the Cedars-Sinai iPSC Core.

Clinical data will be collected and curated through the NeuroBank system at the Massachusetts General Hospital, and cell lines will be developed at Cedars-Sinai in Los Angeles. Currently, participating clinical sites in this effort include the Cedars-Sinai Board of Governors Regenerative Medicine Institute, Columbia University Medical Center, Duke Medical Center, Houston Methodist, the Scotland ALS clinic network, University of Minnesota and Hennepin County Medical Center, University of Utah, University of Washington, and Washington University in St. Louis.

The project is being funded through Biogen’s $30 million strategic alliance with CUMC and $3.5 million from the ALS Association. The ALS Association’s commitment comes from funds raised directly through the Ice Bucket Challenge.

Thursday, August 13, 2015

Source: iStock/©dmbaker

Roche said today it plans to acquire GeneWEAVE for up to $425 million, in a deal intended to strengthen its offerings in clinical microbiology diagnostics.

Through the acquisition, Roche said, it will be better able to fight drug-resistant bacteria because it will own GeneWEAVE’s Smarticles™ technology. Smarticles is a class of molecular diagnostics designed to quickly identify multidrug-resistant organisms (MDROs) and assesses antibiotic susceptibility directly from clinical samples, without the need for traditional enrichment, culture, or sample preparation processes.

GeneWEAVE’s first system in development using the technology, the vivoDx, is a fully automated, random-access system designed for laboratories addressing MDRO detection and antibiotic therapy guidance. The technology is currently being evaluated in multiple sites across the U.S.

“With GeneWEAVE, we further strengthen our microbiology diagnostics offerings with cutting-edge technology that will aid in the fight against drug-resistant bacteria. This technology has the potential to provide healthcare professionals access to quick and accurate diagnoses that can lead to rapid, informed treatment decisions,” Roland Diggelmann, COO of Roche Diagnostics, said in a statement.

Roche has agreed to pay GeneWEAVE shareholders $190 million upfront and up to $235 million in payments tied to achieving product-related milestones.

The deal is subject to customary closing conditions. Once closed, GeneWEAVE will be integrated into Roche Molecular Diagnostics, Roche said.

Based in Los Gatos, CA, GeneWEAVE is a privately-held in vitro diagnostics company focused on diagnostic solutions for advancing clinical microbiology. Last year, the company completed a $12 million series B financing led by Decheng Capital with participation by existing investors Claremont Creek Ventures and X Seed Capital.

“Roche is the ideal company to deliver on the promise of our Smarticles technology. We are fully committed to the continued success of GeneWEAVE’s employees, products, and pipeline,” added GeneWEAVE CEO Steve Tablak.

Roche’s acquisition of GeneWEAVE is the pharma’s second deal this year focused on fighting drug-resistant “superbugs.”

In January, Roche obtained rights from Meiji Seika Pharma and Fedora Pharmaceuticals to develop and commercialize the Phase I beta-lactamase inhibitor OP0595 worldwide except Japan, as part of a treatment designed to fight bacterial resistance to antibiotics. The deal could generate up to $750 million for Meiji and Fedora.

Also, since November 2013, Roche has partnered with Polyphor to develop and commercialize a macrocycle antibiotic designed to fight bacterial infections linked to the multidrug-resistant Pseudomonas species—an up to CHF 500 million ($511.8 million) alliance for Polyphor. In June, Polyphor CEO Michael Altorfer, Ph.D.—a onetime Roche research scientist who took office in March—told Bloomberg News his company may consider an initial public offering should financial markets remain healthy and clinical results prove promising for the co-developed compound, called POL7080.

Tuesday, August 11, 2015

Vera Kuttelvaserova/Fotolia

The Jackson Laboratory (JAX) will partner with several collaborating institutions to establish a new Center for Precision Genetics, to be launched through a five-year, $9,971,936 grant from the NIH.

The new center will work toward the goal of finding solutions for life-threatening and genetically complex human diseases through new approaches to developing precision models of disease, the Laboratory said.

JAX said yesterday it envisions the Center as the hub of an international, multidisciplinary team that includes geneticists and genetics technology experts, molecular and computational biologists, clinical experts in specific disease areas and global leaders in the development of precision mouse models of disease.

Collaborators will include researchers from Emory University, Cedars-Sinai Medical Center, University of California San Diego, Columbia University Medical Center, Nationwide Children's Hospital, University of Massachusetts Medical School, and University of California San Francisco.

“The Center will generate new disease modeling processes and pipelines, data resources, research results and models that will be swiftly shared through JAX’s proven dissemination pipelines to accelerate translation to medical benefit,” Jackson Laboratory President and CEO Edison Liu, M.D., said in a statement.

The new center will draw upon JAX expertise in mammalian genetics and disease modeling, as well as the human clinical samples, data, and collaborations generated by The Jackson Laboratory for Genomic Medicine in Farmington, CT, which opened its $111 million permanent facility last year.

The NIH grant is envisioned as “startup” money for the new Center. The first year’s funding of $1,993,006 will launch six projects, and will pay for several JAX core scientific services including a bioinformatics pipeline, to improve the precision of disease models and the efficiency of preclinical pipelines.

“In order to advance the paths to therapies for previously incurable diseases, we intend to embrace a full range of technologies from reliable yet cutting-edge technological platforms to ambitious high-risk, high-reward platforms that are required to get the job done,” added JAX Professor Wayne Frankel, Ph.D., principal investigator of the grant.

Monday, August 10, 2015

frank peters/Fotolia

Illumina said today it will acquire GenoLogics Life Sciences Software, a developer of laboratory information management systems (LIMS) for life science organizations, in a deal intended to strengthen the buyer’s portfolio of genetic analysis solutions. The price was not disclosed.

GenoLogics’ Clarity LIMS™ software, adopted by more than 120 genomic labs worldwide, is designed to enable lab efficiencies and improved sample throughput with increased accuracy, fast turnaround, sample traceability, and preconfigured instrument integrations.

“Adding GenoLogics’ products to Illumina’s portfolio is another example of our continued commitment to bring innovative sample-to-answer solutions to research and clinical labs,” Illumina President Francis DeSouza said in a statement. “The acquisition of GenoLogics demonstrates Illumina's commitment to drive the adoption of sequencing in new markets and improve the genomic information workflow."

Added GenoLogics CEO Michael Ball: “This acquisition will enable us to widen our distribution, accelerate our product development, and provide even greater support to the Clarity LIMS community."

Illumina said the deal is expected to close by the end of August, and builds on years of partnerships between the companies. In 2011, Illumina became an investor in GenoLogics by leading an $8 million financing round. GenoLogics said at the time it would use the funding to accelerate product development for future clinical applications and new desktop sequencing systems.

A more recent example of a partnership involving the companies is Clarity LIMS X, an edition of its laboratory informatics platform launched on July 20. Optimized for use with Illumina SeqLab, Clarity LIMS X is designed to provide rapid scaling with automation and business logic built into preconfigured HiSeq X Series workflows. Clarity LIMS X Edition also provides e-signature, audit trails, and patient data security, with the goal of being suitable for regulated environments.

GenoLogics will become part of the Illumina Enterprise Informatics business to be led by Sanjay Chikarmane, svp and general manager of enterprise informatics.

Illumina said it accounted for the GenoLogics acquisition in updating its 2015 financial guidance to investors on July 21. The sequencing giant raised its projections for non-GAAP earnings per diluted share to between $3.39 and $3.45—up from between $3.36 and $3.42 as April 21, when first-quarter results were released, and well above the $3.12 to $3.18 range initially projected for 2015 when fourth-quarter and full-year 2014 results were released on January 27.

Tuesday, August 04, 2015

Image 1: MRI of the brain of a healthy child: gray matter is pale gray and white matter is dark gray. Image 2: MRI of the brain of a child with cerebral palsy: red arrows show scarring over the central gray matter leading to stiffness and problems in the coordination of movements. [McGill University Health Centre]

Cerebral palsy (CP) is the most common form of physical disability in children, with an incidence rate of approximately two cases for every 1,000 live births. Historically, CP has been attributed to an array of factors such as asphyxia, stroke, and infections in the developing brains. However, researchers from The Hospital for Sick Children (SickKids) and the Research Institute of the McGill University Health Centre (RI-MUHC) have uncovered evidence for genetic causes of CP that may precipitate a change in the clinical diagnostics for children and expecting mothers.  

"Our research suggests that there is a much stronger genetic component to cerebral palsy than previously suspected," explained lead author Maryam Oskoui, M.D., pediatric neurologist at The Montreal Children's Hospital (MCH) of the MUHC and co-director of the Canadian Cerebral Palsy Registry. "How these genetic factors interplay with other established risk factors remains to be fully understood. For example, two newborns exposed to the same environmental stressors will often have very different outcomes. Our research suggests that our genes impart resilience or conversely a susceptibility to injury."

The findings from this study were published recently in Nature Communications through an article entitled “Clinically relevant copy number variations detected in cerebral palsy.”

The investigators performed genetic tests on 115 children with CP, many of whom had been previously identified with other risk factors as a cause for their disease. DNA tests were also performed on the children’s parents, in order to paint a more comprehensive picture of the genetic background for CP. The researchers found that about 10% of the patients had copy number variations (CNVs) in clinically relevant genes.

"When I showed the results to our clinical geneticists, initially they were floored," said Stephen Scherer, Ph.D., principal investigator on the current study and Director of The Centre for Applied Genomics (TCAG) at SickKids. "In light of the findings, we suggest that genomic analyses be integrated into the standard of practice for diagnostic assessment of cerebral palsy."

CNVs are structural alterations to an individual’s genome that lead to deletion, additions, or some reorganization of gene sequences that produces aberrant genetic products. Typically, CNVs occur in less than 1% of the general population but are increasingly being looked at risk factors, as they are associated with and array of genetic disease states.

"It's a lot like autism, in that many different CNVs affecting different genes are involved which could possibly explain why the clinical presentations of both these conditions are so diverse," noted Dr. Scherer. "Interestingly, the frequency of de novo, or new, CNVs identified in these patients with cerebral palsy is even more significant than some of the major CNV autism research from the last 10 years. We've opened many doors for new research into cerebral palsy."

While the researchers were excited by their findings, they are now urging the clinical community to reevaluate the diagnostic parameters surrounding CP, as they noted that their CNV data would have impacted the diagnosis or classification in almost 10% of the patients they studied. 

"Finding an underlying cause for a child's disability is an important undertaking in management," stated co-author Michael Shevell, M.D. co-director of the Canadian Cerebral Palsy Registry and chair of the Department of Pediatrics at the MCH-MUHC. "Parents want to know why their child has particular challenges. Finding a precise reason opens up multiple vistas related to understanding, specific treatment, prevention and rehabilitation. This study will provide the impetus to make genetic testing a standard part of the comprehensive assessment of the child with cerebral palsy."

Emil Salazar

Monday, August 03, 2015

With NGS diagnostics, the onus on the lab is shifted considerably from hypothesis-driven diagnosis to the interpretation of more data-rich results. [Fotolia.com/© ktsdesign]

If molecular diagnostic tests are to keep pace with fast-evolving microbes, they will have to find an “extra gear.” Existing gears—single pathogen tests and multiplexed panels—have their advantages, mostly with respect to specificity. But specificity is of little help when one is chasing a moving target, as one is obliged to do when typing pathogens or profiling resistant strains. To keep up with such elusive quarry, molecular diagnostics may need to shift to next-generation sequencing (NGS).

Already, NGS is moving into the clinical laboratory, improving the responsiveness of disease control in healthcare settings, and promising to advance the personalization of patient therapy. And now NGS is poised to go yet farther, nimbly bypassing obstacles that have slowed molecular testing’s progress.

For the rest of the story, click here.

Kevin Mayer

Monday, August 03, 2015

Guardant360, Guardant Health’s pan-cancer blood test, is designed to help oncologists prescribe the right treatments at the right time based on the changing genetics of a patient’s cancer. The test does not rely on biopsies, which are risky and costly and typically fail to capture genetic changes that may emerge over time or in response to several cycles of therapy. Instead, the test uses blood samples, which constitute a relatively safe and convenient source of genetic information, one that can be tapped at frequent intervals.

The phrase “information superhighway” sounds quaint nowadays, but only because digital communications has evolved so quickly. Discussion of things digital, once preoccupied with network access and data throughput, is now focused on life-changing applications, such as social networking and data-mining. A similar transition—from speed as a problem to speed as an enabler—may soon be underway in cancer genomics. When this transition is realized, cancer genomics will be less about technicalities, and more about patient benefits.

Until recently, cancer genomics relied almost exclusively on the sequencing of tumor biopsy material. Only this material, acquired by means of inherently difficult and potentially dangerous procedures, could yield actionable information on cancer-associated DNA alterations.

Unfortunately, this material is often hard to obtain, so serial tumor biopsies remain impractical, effectively denying doctors and their patients the benefits of tracking cancers over time.

For the rest of the story, click here.

Monday, August 03, 2015

A three-protein biomarker panel has been established that is able to screen urine samples for signs of early-stage pancreatic cancer. [iStock/© David Marchal]

Raising hopes for a simple, noninvasive, inexpensive, and easily repeatable test for pancreatic cancer, scientists at Barts Cancer Institute, Queen Mary University, have developed a three-protein biomarker panel that can screen urine samples to identify pancreatic cancer when it is still in its early stages. The panel, the scientists say, has already demonstrated better than 90% accuracy. Moreover, it readily distinguishes between pancreatic cancer and chronic pancreatitis, conditions that are easily mistaken for each other.

The scientists settled on just three proteins after conducting proteomic analyses of 488 urine samples—192 from patients with pancreatic ductal adenocarcinoma (PDAC), 92 from patients with chronic pancreatitis, 87 from healthy volunteers, and 117 samples from patients with other benign and malignant liver and gall bladder conditions.

The urine samples were subjected to assays using GeLC-MS/MS (in-gel tryptic digestion followed by liquid chromatography-tandem mass spectrometry) and ELISA. Initially, around 1,500 proteins were identified, with approximately half being common to both male and female volunteers. Of these, three proteins—LYVE1, REG1A, and TFF1—were selected for closer examination.

Each of the three proteins was elevated in urine samples from PDAC patients, but not in urine samples from healthy patients. Patients suffering from chronic pancreatitis had significantly lower levels than cancer patients.

Combining the three proteins, the scientists discovered, yielded a robust panel. The panel’s performance was described August 3 in the journal Clinical Cancer Research, in an article entitled, “Identification of a Three-Biomarker Panel in Urine for Early Detection of Pancreatic Adenocarcinoma.”

“When comparing PDAC with healthy urine specimens, the resulting areas under the receiver-operating characteristic curves (AUC) of the panel were 0.89 in the training (70% of the data) and 0.92 in the validation (30% of the data) datasets,” wrote the authors. “When comparing PDAC stage I–II with healthy urine specimens, the panel achieved AUCs of 0.90 and 0.93 in the training and validation datasets, respectively.”

At present, noninvasive biomarkers for early detection of PDAC are not available. The biomarker panel established by the Barts Cancer Institute scientists, however, shows promise.

“We've always been keen to develop a diagnostic test in urine as it has several advantages over using blood. It's an inert and far less complex fluid than blood and can be repeatedly and non-invasively tested,” said lead researcher Tatjana Crnogorac-Jurcevic, M.D., Ph.D. “It took a while to secure proof of principle funding in 2008 to look at biomarkers in urine, but it's been worth the wait for these results. This is a biomarker panel with good specificity and sensitivity, and we're hopeful that a simple, inexpensive test can be developed and in clinical use within the next few years.”

The team is hoping to conduct further tests on urine samples from people in high-risk groups, to further validate the study findings. Dr. Crnogorac-Jurcevic is also keen to access samples of urine collected from volunteers over a period of 5–10 years. By examining samples from donors who went on to develop pancreatic cancer, this longitudinal information will allow the researchers to see if the three-biomarker signature is present during the latency period—the time between the genetic changes that will cause the cancer to develop and the clinical presentation.

With few specific symptoms even at a later stage of the disease, more than 80% of people with pancreatic cancer are diagnosed when the cancer has already spread. This means they are not eligible for surgery to remove the tumor—currently the only potentially curative treatment.

Patients are usually diagnosed when the cancer is already at a terminal stage, but if diagnosed at stage II, the survival rate is 20%, and at stage I, the survival rate for patients with very small tumors can increase up to 60%. It is hoped that with early detection, the survival rate for pancreatic cancer will improve. At present, only about 3% of patients found to have pancreatic cancer survive more than five years.

Jeffrey S. Buguliskis, Ph.D.

Friday, July 31, 2015

Genetic neurologic diseases may be rare, but new advances in genomic technology are making identifying them a more common event for clinical medicine. [ National Institute of Neurologic Disorders and Stroke]

Contained within the convoluted mass that resides in our skulls is not only the entirety of autonomic muscular signals that control our life-sustaining functions, but arguably more important, at least from an existential point of view, the chemo-electrical constituents that define every individual’s personality. Most often this is why the effects from neurologic disorders like Alzheimer’s disease and amyotrophic lateral sclerosis go far beyond the debilitating neurodegenerative symptoms and often dehumanize patients through the systematic eradication of their personality.

In relation to all other organ systems, our understanding of the brain and associated neuronal pathways is in its infancy. However, advances in technology, genetic analysis methods, and surges in funding and awareness have begun to create a critical mass of information that may well engender an array of revelations within the neuroscience field.

For instance, a recent project has begun to generate a comprehensive map of the neural connections within the brain by harnessing the power and speed of next-generation sequencing (NGS) technology. 

For the rest of the story, click here.

MaryAnn Labant

Friday, July 31, 2015

Genetic information is already being applied clinically, with genomic testing on tumors providing insights into treatment routes, and the knowledge base will continue to grow. But before this technology can be widely adopted and implemented into clinical care, major social, legal, and ethical issues need to be addressed. Thought leaders convened late June at the first Festival of Genomics in Boston to discuss crucial elements of the genomic revolution.

Essentially at some point in the future, individuals will have their complete genome sequenced; the data will be securely stored; and clinicians will reference the information throughout a patient’s lifetime. Doctors will be charged with ordering the tests and will need accessible and easily interpretable reports in order to apply the results in the clinical setting.

For the rest of the story, click here.


Friday, July 31, 2015

The August issue of Clinical OMICs is available now! Check it out by clicking on the link below.

Clinical OMICs Volume 2, Issue No. 8

MaryAnn Labant

Friday, July 31, 2015

Promega, which produces reaction components for PCR-based molecular assays, notes that the quality controls implemented by manufacturers can affect molecular diagnostic assay design and performance. The company adds that as multiplexed assays and panel tests become more common, lot-to-lot reagent consistency will become more important.

Since its invention by Kary B. Mullis in 1985, the polymerase chain reaction (PCR) has become well established, even routine, in research laboratories. And now PCR is becoming more common in clinical applications, thanks to advances in genomics and the evolution of more sensitive quantitative PCR methodologies. Examples of clinical applications of PCR include point-of-care (POC) molecular tests for bacterial and viral detection, as well as mutation detection in liquid or tumor biopsies for patient stratification and treatment monitoring.

Industry leaders recently participated in a CHI conference that was held in San Francisco. This conference—PCR for Molecular Medicine—encompassed research and clinical perspectives and emphasized advanced techniques and tools for effective disease diagnosis.

To kick off the event, speakers shared their views on POC molecular tests. These tests, the speakers insisted, can provide significant value to healthcare only if they support timely decision making.

For the rest of the story, click here.

Thursday, July 30, 2015

New study shows that gender was the most significant attributable source of variation for regulatory elements among immune system genes. [iStock/iofoto]

After the completion of the Human Genome Project, one thing became abundantly clear to scientists: that they had only begun to scratch the surface of how genetic information was processed within cells. In the years since, advances in sequencing techniques have allowed scientists to uncover the underlying regulatory mechanisms that take place from gene expression to protein metabolite end products—the regulome, as it is often referred, encompasses all of these processes.  

Now, researchers from Stanford University have turned their attention to the regulome of the immune system and utilized a newly developed sequencing technique to study how immune genes are toggled on and off and how they are fundamentally different between men and women. Their results revealed some intriguing surprises and may offer new insight into autoimmune disorders.

"Part of why this is possible is a new technology that was invented at Stanford for measuring the accessibility of the genome to regulatory elements," explained the study's senior author Howard Chang, M.D., Ph.D., professor of dermatology at Stanford University.

The findings from this study were published recently in Cell Systems through an article entitled “Individuality and Variation of Personal Regulomes in Primary Human T Cells.”

Interestingly, the Stanford investigators found that some genes are virtually always on while others seemingly sit unused for quite some time. Moreover, they discovered that the genes which switch on and off differently from person to person are more likely to be associated with autoimmune diseases and that men and women use different regulatory elements to turn on many of the immune system genes. These findings led the team to hypothesize that the difference in activity may explain the much greater incidence of autoimmune diseases such as lupus, scleroderma, and rheumatoid arthritis among women.

"We were interested in exploring the landscape of gene regulation directly from live people and look at differences," said Dr. Chang. "We asked, 'How different or similar are people?' This is different from asking if they have the same genes. I would say the majority of the difference is likely from a nongenetic source.”

Dr. Chang continued, stating "but the single greatest predictor for genes' tendency to turn on and off was the sex of the person. In terms of significance, sex was far more important than all the other things we looked at, perhaps even combined."

The Stanford scientists took advantage of a new sequencing technique that Dr. Change helped developed, publishing the initial paper describing the methodology in January, which maps genome-wide chromatin accessibility and was aptly named Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq).  This method allowed the researchers to sample living cells in real time in order to follow their regulatory patterns.  

"In the past, people needed a huge number of cells to do this kind of measurement. You'd actually need a pound of flesh to get certain rare cell types,” stated Dr. Chang. “So you can't get that out of a live person—and certainly not more than once, right?"

"But now," continued Dr. Chang, "you are studying copies of copies; you aren't studying the original cells anymore. Those months of being grown in the lab completely changes how the cells are behaving and so you are no longer looking at the personal. How the laboratory cells behave has nothing to do with what the person just ate, whether they had a fight with their girlfriend or whether they had an infection."

The study looked at T cells from 12 healthy volunteers, measuring the genetic regulatory switches within the immune system of each. Across the 12 healthy volunteers, 7% of the genes were switched on in different patterns from person to person. For each person, these patterns persisted over time, like a unique fingerprint. When the team measured gene activity levels from 30 of the top 500 genes the researchers expected would show gender-influenced activity, they found that 20 of the 30 genes showed significant differential activity between men and women.

Dr. Chang and his colleagues hope that their data will help provide the baseline for future studies that look to determine gene regulatory differences among patients affected with autoimmune diseases.

Friday, July 24, 2015

One of the goals of the Prenatal Quality Foundation’s campaign is to close knowledge gaps among consumers and healthcare providers about novel noninvasive prenatal screening tests. [iStock/© EmiliaU]

The Perinatal Quality Foundation (PQF) has begun a nationwide campaign to improve understanding of the advantages, limitations, and clinically appropriate interpretation of results of noninvasive prenatal screening and other diagnostic tests for pregnant women and their healthcare providers. Quest Diagnostics is the first commercial organization to support the initiative, through a grant.

Campaign officials say they aim to close knowledge gaps among consumers and healthcare providers about a new generation of highly advanced noninvasive prenatal screening tests that identify cell-free fetal DNA in maternal blood, as well as maternal serum screening, chromosomal microarray analysis, and expanded carrier screening. The campaign will also involve the creation of an online patient registry through which women who receive prenatal screening during pregnancy may report results of confirmatory diagnostic tests, primarily chorionic villus sampling or amniocentesis, as well as post-partum outcomes.  The goal is to enable scientists to use this de-identified information to determine the positive and negative predictive value for noninvasive prenatal screens for common aneuploidies such as trisomy 21. 

A tests's predictive value is used to assess whether an individual’s test result is truly positive or negative (or a false positive or false negative), and may be a more important barometer of a test’s clinical value than sensitivity and specificity for conditions that have a low prevalence, such as fetal aneuploidies. In August 2014, Genetics in Medicine published a peer-reviewed study by Quest Diagnostics scientists that found the change that a positive result was a false positive reached as high as 50% for several widely used noninvasive prenatal diagnostic tests, despite sensitivity and specificity rates approaching 100%.

“PQF and Quest Diagnostics share a vision to promote high quality, reliable screening of women during pregnancy,” said Mary Norton, M.D, president of PQF.

“The explosion of novel genetic technologies for assessing pregnancy risks has outpaced the knowledge base women and physicians possess about the advantages and limitations of these tests,” added Douglas S. Rabin, M.D., medical director, women's health, Quest Diagnostics. “As a leader in women’s health services and an innovator of genetic testing, we recognize that we have a role to play in closing this knowledge gap so that women can take the most well-informed action possible to promote a healthy outcome for her and her family. We are thrilled to help PQF kick off this important program.” 

Friday, July 24, 2015

Swiss researchers have developed a technique to use firefly luciferase as a quick and inexpensive medical diagnostic tool. [iStock/huePhotography]

Within the clinical arena, accurate and sensitive diagnostics are paramount to developing effective treatment regimens for patients. Physicians often require quick and reliable ways to discern if patients are afflicted with a specific ailment. Although many such detection methods currently exist, they often require a large investment of time, work, and/or money.    

Now, scientists from the Swiss Federal Institute of Technology in Lausanne (EPFL) have chemically modified the enzyme responsible for fireflies to create light and forced it to seek out target biological molecules, ultimately producing a light signal. The results of their effort should provide clinical diagnostics with a cheap, simple, and highly accurate detection system that could have broad applications for the field.  

 The Swiss researchers were able to add a small chemical tag onto the luciferase enzyme, which is able to detect target proteins, producing a light signal that is able to be seen with the naked eye—eliminating the need for expensive and complex detection equipment.

"You can think of the tagged luciferase as a cyborg molecule," explained Kai Johnsson, Ph.D., Professor in the Institute of Chemical Sciences and Engineering at EPFL. "Half bio, half synthetic. How could you make luciferase sensitive to the presence of another protein just through mutations? It's a lot of work. With this chemical trick, all we have to worry about is designing an appropriate tag that can recognize the target protein."

The findings from this study were published recently in Nature Communications through an article entitled “Modulating protein activity using tethered ligands with mutually exclusive binding sites.”

“The approach is based on synthetic ligands that possess two mutually exclusive binding sites, one for the protein of interest and one for the effector,” the scientists stated. “Tethering such a ligand to the protein of interest results in an intramolecular ligand–protein interaction that can be disrupted through the presence of the effector.”

Specifically, Dr. Johnsson and his team were able to develop a luciferase molecule controlled by the human carbonic anhydrase enzyme, whose activity can be regulated by proteins or small molecules in vitro, on living cells, and on bioluminescent biosensors.

The investigators noted that the ability to modulate protein activity on the surface of living cells creates opportunities and applications well beyond in vitro assays. However, they caution that while their results were exciting this technique will not be usable for every protein and is restricted to those proteins for which ligands with mutually exclusive binding sites either currently exist or can be created. 

“This is a generalized design," said Kai Johnsson. "It shows how you can exploit synthetic chemistry to create sophisticated biosensor proteins."

Monday, July 20, 2015


Researchers at the Norwich, U.K.-based Genome Analysis Center (TGAC) say they have developed a unique bioinformatics approach for identifying associations between molecules from a range of vast data sources. Their report (“ONION: Functional Approach for Integration of Lipidomics and Transcriptomics Data”), published in PLOS1, described studies that focused on measuring metabolism in tissues under varying conditions, e.g. genetics, diets, and environment.

Opposed to current methods that apply statistical analysis to data sets as a whole, the proposed workflow breaks the initial data into smaller groups determined by known molecular interactions. Statistical methods can then be applied to these groups resulting in more accurate results than if the analysis had been applied to the whole dataset. This technique has been shown to improve the detection of genes related to lipid metabolism on an example mouse nutritional study that increases our understanding of biochemical fluctuations by 15%, according to the scientists.

Identifying associations between metabolites and genes is crucial to understanding processes in the cell. However, uncovering these relationships is a complex task, especially when integrating data that concerns various types of molecules. Adding to this complexity is the vast quantity of data available for analysis, a result of the development of new experimental high-throughput techniques.

Initially, the molecular workflow will be applied to research into the benefits of broccoli for prostate cancer, in collaboration with the Institute of Food Research. As well as being applied to studying the health benefits of flavonoids, which are plant metabolites found in a variety of fruits and vegetables, in collaboration with the University of East Anglia.

“By improving our capability to integrate data from various sources and identify links between metabolites and genes, this workflow will provide a more detailed diagnosis of cellular metabolism and gene expression in biological processes,” said study co-author Wiktor Jurkowski, Ph.D., integrative genomics group leader at TGAC. "Knowledge gathered in molecular networks can be harnessed to improve data integration and interpretation."

Dr. Jurkowski explained that his team’s approach, integrating transcriptomics and metabolomics data, will help interpret signals measured by omics techniques to extend our knowledge of processes under specific biological conditions.

“This will benefit biologists in interpreting data, creating better hypothesizes, and pinpointing genes and metabolites involved to unravel the mechanism of interest,” he continued. "This is a proof-of-concept study and we are currently working towards improving the group generation strategy for spare areas of the interactome and less annotated species. We are applying this and other molecular network approaches to data generated in collaborative projects across Norwich Research Park."

Monday, July 20, 2015

Source: iStock/© GoodLifeStudio

Affymetrix and Cytox have agreed to collaborate on developing and commercializing a blood-based genetic assay for research in diagnosis and prognosis of Alzheimer’s disease (AD) and mild cognitive impairment (MCI).

The value of the collaboration was not disclosed by Cytox, which announced the partnership today.

The collaboration is designed to combine Affymetrix’ technology, know-how and marketing support with Cytox’ expertise in developing tests to identify individuals at risk of cognitive decline, AD and other dementias.

Cytox said it has identified a novel panel of DNA sequence variations or single nucleotide polymorphisms (SNPs) in genes influenced by rapamycin, linked to the mTOR signaling pathway. Cytox has data suggesting that an assessment of disease risk may be possible using a customized genetic variation SNP panel associated with mTOR signaling and other pathways, the company added.

A key goal, according to Cytox, is the validation of the panel for future at risk individuals with MCI.

“Our early research studies developed with our partners at University College London and University of Birmingham suggest that by using a customized genetic variation (SNP) panel, it may be possible to better assess the risk of an individual developing AD or MCI,” Cytox CEO Richard Pither, Ph.D., said in a statement.

Dr. Pither added that Affymetrix’ Axiom® genotyping platform was “ideally suited for use in a blood-based test for researchers interested in AD and MCI risk stratification and longer-term diagnostic and prognostic use.”

According to Affymetrix, its Axiom Genotyping Solution offers pre-designed arrays covering more populations than any other technology. Users can use variants they provide or choose SNPs from the company’s Axiom Genomic Database.

“The partnership with Cytox will allow us to extend our offering into the important AD and dementia research market with a significant new application,” added Michael Nemzek, vp of strategic marketing, genotyping, at Affymetrix.

Friday, July 17, 2015

Source: iStock/© angelhell

Scientists at the Aortic Institute at Yale tested the genomes of more than 100 patients with thoracic aortic aneurysms, a potentially lethal condition, and provided genetically personalized care. They say their work will also lead to the development of a "dictionary" of genes specific to the disease, according to researchers.

Their study (“Routine Genetic Testing for Thoracic Aortic Aneurysm and Dissection in a Clinical Setting”) is published online in The Annals of Thoracic Surgery.

Experts have known for more than a decade that thoracic aortic aneurysms run in families and are caused by specific genetic mutations. Until recently, comprehensive testing for these mutations has been both expensive and impractical. To streamline testing, the Aortic Institute collaborated with Allen Bale, M.D., of Yale's department of genetics to launch a program to test whole genomes of patients with the condition.

Over a period of three years, the researchers applied whole exome sequencing (WES) to more than 100 individuals with these aneurysms. "To our knowledge, it's the first widespread application of this technology to this disease," said lead author and cardiac surgeon John A. Elefteriades, M.D., director of the institute.

The researchers detected four mutations known to cause thoracic aortic aneurysms. "The key findings are that this technology can be applied to this disease and it identifies a lot of patients with genetic mutations," added Dr. Elefteriades.

Additionally, the testing program uncovered 22 previously unknown gene variants that likely also contribute to the condition. Using the test results, the clinicians were able to provide treatment tailored to each patient's genetic profile. "Personalized aortic aneurysm care is now a reality," noted Dr. Elefteriades. The personalized care ranged from more frequent imaging tests to preventive surgery for those most at risk. "Patients who have very dangerous mutations are getting immediate surgery," he explained.

Given that aneurysm disease is a highly inherited condition, affecting each generation, the researchers offered testing to family members of patients, and found mutations in relatives with no clinical signs of disease.

The researchers anticipate identifying more gene variants over time, accumulating a whole dictionary of mutations. "In a few years, we're going to have discovered many new genes and be able to offer personalized care to an even greater percentage of aneurysm patients," said Dr. Elefteriades.

Monday, July 13, 2015

Source: © Kheng Guan Toh/Fotolia

Many couples who struggle with infertility also suffer uncertainty. Infertility may arise from paternal or maternal factors, or both. When this uncertainty persists, couples may be unable to start the most appropriate fertility treatments. And the birth of a healthy child may be delayed.

To help resolve uncertainty—and guide prospective parents to the right fertility treatments—scientists propose the use of a new kind of fertility test. It involves examining sperm RNA by means of next-generation sequencing.

To date, evaluation of male infertility has lagged evaluation of female infertility, even though the American Society for Reproductive Medicine holds that infertility is due in equal measure to male and female factors. Male factors that have been subject to scrutiny have been limited to a few semen parameters, in addition to a review of the prospective father’s reproductive and family histories.

Existing semen parameters—sperm concentration, motility, and morphology—are useful mainly for the diagnosis of obvious cases of male infertility. The new test, however, can provide an objective measure of the paternal contribution to infertility. It was developed in the laboratory of Stephen Krawetz, Ph.D., a researcher at Wayne State University, in collaboration with scientists from CReATe Fertility Center, University of Toronto, Harvard University, and Georgia Regents University.

The scientific team presented their results July 8 in Science Translational Medicine, in an article entitled, “Absence of sperm RNA elements correlates with idiopathic male infertility.”

“We assessed spermatozoal RNAs from 96 couples presenting with idiopathic infertility and identified the final reproductive outcome and sperm RNA elements (SREs) reflective of fecundity status,” the authors wrote. “The absence of required SREs reduced the probability of achieving live birth by timed intercourse or intrauterine insemination from 73 to 27%.”

The authors added, however, that the absence of these same SREs does not appear to be critical when using assisted reproductive technologies such as in vitro fertilization with or without intracytoplasmic sperm injection.

“Upon validation, [next-generation sequencing of sperm RNA] may help to identify those couples who may benefit from assisted reproductive technologies and those couples who may be successful with minimal intervention,” said Dr. Krawetz. “It is our goal to use this technology to reduce both the time to live birth of a healthy child and the cost when couples seek infertility treatment, so as to reduce the stress on the couple.”

About 13% of couples of reproductive age experience fertility problems. When fertility problems are identified, the usual response is to conduct extensive evaluation of the female partner before embarking on fertility treatment. But now, with the new test, the male partner may receive additional attention, beyond the evaluation of the usual semen parameters.

In the current study, about 30% of the idiopathic infertile couples presented an incomplete set of required SREs, suggesting a male component as the cause of their infertility. Conversely, analysis of couples that failed to achieve a live birth despite presenting with a complete set of SREs suggested that a female factor may have been involved. This was confirmed by their diagnosis, noted the authors of the Science Translational Medicine article.

According to Dr. Krawetz, the diagnostic potential of next-generation sequencing of sperm RNA indicates this method is "better suited to the task" of analyzing the male's role in infertility, and is a step toward personalized precision reproductive medicine that may help guide the couple to their successful treatment.

Sperm RNA analysis at present is technically challenging, but it is being automated. The technique could become part of a routine examination as "we move toward personalized and precision medicine," Dr. Krawetz asserted. While the test is experimental, it has the potential for cost savings for both the patients and the healthcare system.

The next step, emphasized a Wayne State University press announcement, is to expand to a prospective blinded study and to begin to define a set of markers that may be predictive of assisted reproduction outcomes.

Friday, July 10, 2015

Source: iStock/© Eraxion

Researchers at Johns Hopkins Kimmel Cancer Center report that in a genome-sequencing study of pancreatic cancers and blood in 101 patients at least one-third of the patients' tumors have genetic mutations that may someday help guide precision therapy of their disease. Results of blood tests to detect DNA shed from tumors, they add, also predicted cancer recurrence more than half a year earlier than standard imaging methods.

"Pancreatic cancer has one of the highest death rates among cancer types. Many people think there are no treatment options, but our study shows that genomic sequencing of patients' tumor samples may identify mutations that match the target of certain clinical trials or drugs that are more precisely appropriate for these patients," points out Victor Velculescu, M.D., Ph.D., a professor of oncology and pathology at the Johns Hopkins University School of Medicine and co-director of the Kimmel Cancer Center's Cancer Biology Program.

Dr. Velculescu cautions that for patients to realize the treatment-guiding benefit of genomic sequencing, researchers will first need to develop larger, multi-institutional trials using experimental or approved drugs that target the mutations identified by the Johns Hopkins-led team. Currently, pancreatic cancer is treated surgically, and with radiation and chemotherapy.

Results of their sequencing study (“Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients”), using data generated by Personal Genome Diagnostics, a company co-founded by the Johns Hopkins researchers, are published online in Nature Communications.

Pancreatic cancers are diagnosed in nearly 50,000 people in the U.S. each year. Fewer than 10% of them survive more than five years past diagnosis, and most patients are prescribed therapies based on their disease stage, not the genomic qualities of their cancer.

For the sequencing study, Dr. Velculescu and his colleagues collected tumor samples and normal DNA from 101 patients with stage II pancreatic cancer whose tumors were surgically removed at the University of Pennsylvania, the University of Copenhagen and Washington University at St. Louis.

The team sequenced the whole exomes of 24 of the 101 patients' tumor and normal DNA to find genes that drive the cancer's growth and were commonly mutated among the group. Then, the group sequenced tumor and normal DNA in the rest of the patients, specifically looking for mutations in a subset of cancer-promoting genes.

Pancreatic cancer tissue is often difficult to sequence, and mutations are challenging to find, says co-author Mark Sausen, Ph.D., a former graduate student in Dr. Velculescu's laboratory when the research was completed and who is now employed by Personal Genome Diagnostics. To overcome this, the team used sensitive deep sequencing methods that analyzed each nucleotide base more than 750 times to identify mutated genes.

The team reported that 98 of the 101 patients had tumor mutations in known pancreatic cancer genes, TP53 and KRAS. So far, Dr. Sausen says, drugs that target these two mutations have had disappointing results. However, the study identified 38 patients with mutations in genes such as ERBB2, PI3KCA, BRCA2, AKT1 and AKT2 that are the focus of drugs already approved for other diseases, or of ongoing or published clinical trials.

Dr. Velculescu says previously published research by Johns Hopkins scientists provided proof of principle of the potential value of drug therapies precisely selected for their ability to address specific cancer mutations. They sequenced the tumor of a patient with pancreatic cancer and found mutations in the PALB2 gene, which is involved in repairing DNA damage. When physicians treated the patient with mitomycin C, a DNA-damaging drug, the patient survived more than five years past diagnosis, well beyond average survival estimates.

In further experiments, the scientists collected blood samples every three months from 51 patients with early-stage pancreatic cancer (44 of the 101 subjects who were sequenced in the current study plus seven additional patients) for up to three years. Some 22 of the 51 (43%) had detectable levels of cancer DNA in their blood at the time of their diagnosis. Furthermore, the scientists predicted patients' cancer recurrence after surgery six months earlier by looking for cancer DNA shed into the blood, compared with standard imaging.

"The sooner we find recurrence, the sooner we can intervene with additional therapies," says Dr. Velculescu. "Research on liquid biopsies using blood samples is evolving, but these initial results offer hope for developing methods for early detection of residual disease and real-time monitoring of patients' cancers."

He says that larger clinical trials are also needed to determine the clinical effectiveness of the blood-based DNA tests.

Gail Dutton

Thursday, July 02, 2015

Working with Roche, Foundation Medicine is in the early stages of advancing tests to identify biomarkers to predict response to immunotherapy.

Foundation Medicine plans to fundamentally change the way cancer is diagnosed and treated by providing the molecular information physicians need to match therapies to conditions.

“Cancer is a genomic disease,” Steve Kafka, Ph.D., COO, points out, but until recently its primary descriptor has been its location in the body. That has spawned research focused on prostate cancer, breast cancer, colon cancer, etc. that didn’t look at the genomic causes of the disease. Zeroing in on cancer genomics is a paradigm shift.

“The important thing is to understand the molecular drivers of cancer. Therefore, our tests are comprehensive across the genome,” Dr. Kafka says. “Our approach is information-based. We want to understand each patient’s cancer at a deep molecular level, drawing on scientific and medical literature and targeted drug therapies to help researchers and physicians make the best patient-selection and treatment decisions.”

For the rest of the story, click here.

Rodrigo Barnes

Thursday, July 02, 2015

A new generation of information technology is required to move next-generation sequencing from academic discussion to diagnostic use. [© Mehmet Pinarci (creativecommlons.org/licenses/by/2.01/)]

I’ve been involved in lots of discussions about the future lately. Particularly the future of medicine, the future of data science, and how these topics merge around the potential for genomics to contribute to clinical care. It has long been anticipated, but that translation from science to treatment isn’t quite there yet.

Next-generation sequencing (NGS), particularly whole genome or whole gene sequencing, is poised to impact clinical services beyond research projects and clinical trials. Clear applications exist in rare disease diagnosis and cancer treatment decision support, as well as in stratification of treatment in other disease areas. The problem that exists now is that genomics is still largely used and discussed by academia, and not intended for diagnostic use. We understand the applications, but we still need to make the leap from experimental to mainstream; to demonstrate how and why genomics is the future of medicine.

To do this, healthcare providers need to take control of the operation of genomics, to drive quality upwards and encourage new applications of genomic sequencing in new disease areas.

For the rest of the story, click here.

Alex Philippidis

Thursday, July 02, 2015

For Invitae, a factor in starting patient-pay pricing was the launch of Color Genomics’ $249 saliva test kit for genes linked to breast and ovarian cancers. [iStock/© Susan Chiang]

New tests and pricing plans are reshaping the genetic testing landscape, with Invitae offering non-insurance patients a lower price for its genetic tests, and two other developers launching new tests priced in the hundreds of dollars.

At $475 per indication, patients can access Invitae’s full menu of tests, covering a single diagnostic service with more than 200 genes assessed for any of several indications. These include cancer, cardiology, neurology, pediatric genetics, hematology, and other rare conditions. To take advantage, patients must register with the company, pay online themselves, and have their tests ordered by a clinician.

“We started driving down prices, and we’ve made it clear we intend to continue to drive down the prices to multiple price points in multiple disease areas,” Invitae President and COO Sean George told Clinical OMICs. “Exomes and genomes will cost more than smaller panels, but in general, rapidly driving down the price of indication-based testing is what we foresee in coming years.”

For the rest of the story, click here.

Stephen C. Peiper, M.D., and Erica S. Johnson, Ph.D.

Wednesday, July 01, 2015

In the East Room of the White House, January 30, 2015, U.S. President Barack Obama announced his plans to invest $215 million in precision medicine research. [White House Tumblr Feed]

Healthcare in the United States is currently in the throes of radical change after years of organizational stasis and disheartening metrics. Our healthcare system was ranked 37th among 191 member states for health outcomes, responsiveness, and fairness of distribution by the World Health Organization in 2000, and 31st in a group of 51 for efficiency and life expectancy by Bloomberg in 2014. Recently, however, diverse forces started to converge, leading to forecasts of a “perfect storm” of healthcare reinvention.

These forces include 1) an emphasis on value and outcomes for quality of care and patient safety; 2) a shift from reactive disease management to health promotion; 3) a changing compensation model; 4) access to universal health insurance coverage; and 5) availability of state-of-the-art diagnostic technologies and cutting-edge therapies.

For the rest of the story, click here.

Patricia Fitzpatrick Dimond, Ph.D.

Wednesday, July 01, 2015

Source: iStock/Mutlu Kurtbas

As described by the National Institutes of Health (NIH), point-of-care (POC) instruments combine multiple analytical functions into self-contained, portable devices that can be used by nonspecialists to detect and diagnose disease. They can also enable the selection of optimal therapies through patient screening and monitoring of a patient’s response to a chosen treatment. These devices have attracted public and private funding, as well as considerable investment from large diagnostic companies.

Kalorama Information noted that the emerging area of rapid POC molecular testing attracted over $650 million in investments and financings between 2009 and 2013, alone, while a 2014 Frost and Sullivan report predicted that molecular testing, particularly the overall growth of the global infectious diseases diagnostics market, will approach $12.78 billion in 2018.

For the rest of the story, click here.

Jeff Buguliskis, Ph.D.

Wednesday, July 01, 2015

A portable NGS platform would drastically improve the efficiency of diagnosis and stem the spread of infectious disease outbreaks such as Ebola.

You’re a physician working in West Africa for Doctors Without Borders, and a child has been brought into your clinic who is febrile and complaining of a headache, fatigue, and malaise. Given your locale and the current season, two of the most probable diagnoses would be either malaria or Ebola. While neither disease provides a positive prognosis for the patient, Ebola has the capability of spreading rapidly to many other individuals and would require quarantining as soon as possible.

Time is of the essence, but so is accuracy as the panic of an Ebola infection would spread even faster than the disease itself. Moreover, should your prognosis prove wrong and the child actually have malaria, any Ebola therapy would be completely ineffective.

These are real scenarios that many physicians have to face daily and not just in underdeveloped parts of the world. Infectious diseases could just as easily spread (and have) through hospitals, schools, cruise liners, and food preparation plants. While our current monitoring systems are relatively effective at isolating and identifying the offending microbe during an outbreak, speed is always a most welcome ally in the diagnostic instrumentation realm.

For the rest of the story, click here.

Wednesday, July 01, 2015

The July issue of Clinical OMICs is available now! Check it out by clicking on the link below.

Clinical OMICs Volume 2, Issue No. 7

Thursday, June 25, 2015

iStock/© RoBeDeRo

Joshua Harris, co-founder of Apollo Global Management, and his wife, Marjorie, made a $5 million gift to establish the Harris Center for Precision Wellness at the Icahn School of Medicine at Mount Sinai. The center, reportedly the first-of-its-kind at a major U.S. academic medical institution, is part of the Icahn Institute for Genomics and Multiscale Biology. It will develop innovative approaches to health monitoring and wellness management by integrating emerging technologies in digital health, data science, and genomics to enable people’s health to be treated in precise, highly individualized ways. The Center will provide a focus for a network of precision wellness research programs closely tied to clinical initiatives across the Mount Sinai Health System, according to Mount Sinai officials.

"I am honored to establish this new center to support groundbreaking research and innovation at the frontier of health and wellness,” Harris said. “It is an extraordinary opportunity to make a real difference in people’s lives. While access to powerful new digital and molecular tools to track and inform healthcare is growing, a science-driven approach is needed to integrate these new technologies into tools and applications that people can trust and use with confidence.”

“A number of research initiatives already underway at the Icahn Institute are focused on driving a greater understanding of health and wellness,” added Eric Schadt, Ph.D., the Jean C. and James W. Crystal Professor of Genomics at the Icahn School of Medicine at Mount Sinai, and founding director of the Icahn Institute for Genomics and Multiscale Biology. “The new Harris Center will accelerate this momentum toward developing novel tools and approaches enabling precision wellness.”

The Harris Center’s immediate efforts will focus on digital health, molecular profiling, and data science. The Center is evaluating wearable devices to see how reliably they can measure activity, stress, sleep, cognitive functioning, mood, and environmental exposures and using sequencing technology to bring DNA, microbiome, and immune system profiles into predictive models of wellness.

In addition, the Center is preparing to apply advanced analytics and machine learning to the wealth of individualized metrics to produce actionable, data-driven insights into key aspects of wellness, and to help lead the way to a nextgen healthcare that is scalable.

The Harris Center will be directed by Joel Dudley, Ph.D., a genomics and bioinformatics expert at the Icahn Institute, and by Gregory Stock, Ph.D., a life-science entrepreneur and technology-innovation expert recruited to serve as the Center’s co-director.

Dr. Dudley, known for his work in genomic medicine and translational bioinformatics, was recognized by Fast Company in 2014 as one of the world’s 100-most-creative people.

"We are deeply grateful to Mr. Harris for his generosity, vision, and passion,” said Dr. Dudley. “His gift will help realize the promise we see in new digital health technologies such as wearable sensors and mobile applications. By drawing upon the core competencies in genomics, multiscale biology, bioinformatics, data science, population health, and clinical trial design at the Icahn Institute, the Harris Center initiatives will further enhance Mount Sinai’s reputation as one of the world's premier innovators in personalized healthcare. It is exciting to have an opportunity to integrate and apply these emerging technologies in a meaningful and scientific way in the pursuit of optimal wellness, vitality, and preventive care.”

Prior to joining Mount Sinai, the Center’s co-director, Dr. Gregory Stock, was an influential voice at UCLA in national policy debates about the implications of emerging life-science technology. He recently led an industry effort to assay individualized genetic vulnerability to neurobehavioral deficits from chronic low-level exposure to mercury and other environmental toxins.

“It’s a real privilege to help catalyze the shift to predictive, proactive healthcare,” said Dr. Stock, a Research Professor in the Department of Genetics and Genomic Science. “To realize the promise of nextgen digital healthcare now, a focused effort is essential. The timing for the center is perfect: key enabling technologies are arising on a broad front, and a shift to more precise and personalized approaches to wellness is taking shape. Wellness is much more than the absence of disease, and a big-data approach combining information from wearables, lab work-ups and omic panels to better characterize it should be very fruitful in enhancing our health.”

Thursday, June 25, 2015

Artistic interpretation of an exosome carrying DNA/RNA from a cancer cell. [National Institutes of Health]

Precision noninvasive screening tools are paramount to diagnostic medicine for the early detection of potentially life-threating diseases. Now, researchers at The University of Texas MD Anderson Cancer Center have found a protein present on exosomes, which they believe could become a standard diagnostic biomarker for pancreatic cancer.

Typically, exosomes contain DNA, RNA, and protein molecules that often end up within the systemic circulation of patients suffering from cancer. In the current study, scientists were able to isolate and monitor exosomes containing a protein encoded by the glypican-1 gene (GPC1) from the blood of pancreatic cancer patients, which the researchers dubbed, GPC1 + crExos.  

"GPC1+ crExos were detected in small amounts of serum from about 250 patients with pancreatic cancer with absolute specificity and sensitivity, importantly distinguishing patients with chronic pancreatitis from those with early- and late-stage pancreatic cancer," explained senior author Raghu Kalluri, M.D., Ph.D., chair of Cancer Biology at MD Anderson.

The findings from this study were published recently in Nature through an article entitled "Glypican-1 identifies cancer exosomes and detects early pancreatic cancer."

Interestingly, the levels of GPC1+ crExos were significantly lower in patients following surgical removal of the tumor. Moreover, the study examined crExos from healthy donors as well as breast and pancreatic cancer patients—with elevated GPC1+ crExos being observed in both cancers. 

Exosomes represent a versatile and advantageous tool for the study of various cancers, as the vesicles and their contents are relatively stable for long periods of time.

"GPC1+ crExos can be detected and isolated in blood samples that were stored in freezers almost 30 years ago, unlike circulating tumor cells (CTCs) that require large amounts of fresh blood," said Dr. Kalluri. "DNA, RNA, and proteins can be isolated from cancer exosomes isolated from stored specimen for further genetic and biological analyses. Therefore, cancer exosomes are not just a biomarker but isolating them provides a trove of cancer-specific information."

The MD Anderson team made a critical observation once all the results from the current study were fully analyzed, which was that GPC1+ crExos appeared to be a more reliable screening tool than the commonly used CA 19-9 biomarker. Astonishingly, while screening for GPC1+ crExos, the investigators were able to detect the possibility of pancreatic cancer in mouse models at a time when the mice showed no signs of pancreatic disease by MRI.

"Routine screening of the general population for pancreatic cancer using MRIs or CTs would be prohibitively expensive with the likelihood for many false positives," stated co-author David Piwnica-Worms, M.D., Ph.D., chair of Cancer Systems Imaging at MD Anderson. "Our study suggests the potential for GPC1+ crExos as a detection and monitoring tool for pancreatic cancer in combination with imaging, with an emphasis on its application in early detection."

Recent data concerning pancreatic cancer suggests that early detection could be lifesaving as more patients would qualify for surgeries shown to be curative. Since pancreatic cancer is often diagnosed in more advanced stages, only about 15% of patients currently qualify for any type of surgery.   
"Studies comparing stage of disease with outcome following surgery suggest that death rates for pancreatic cancer would be reduced if the disease were diagnosed at an earlier stage," said Dr. Kalluri. "This presents an unprecedented opportunity for informative early detection of pancreatic cancer and in designing potential curative surgical options."

Thursday, June 25, 2015

Source: iStock/© Dead_Morozzzka

Researchers at Johns Hopkins led a proof-of-principle study that successfully identified tumor DNA shed into the blood and saliva of 93 patients with head and neck cancer. Their report (“Detection of somatic mutations and HPV in the saliva and plasma of patients with head and neck squamous cell carcinoma”) is published in Science Translational Medicine.

"We have shown that tumor DNA in the blood or saliva can successfully be measured for these cancers," says Nishant Agrawal, M.D., associate professor of otolaryngology and of oncology at the Johns Hopkins University School of Medicine. "In our study, testing saliva seemed to be the best way to detect cancers in the oral cavity, and blood tests appeared to find more cancers in the larynx, hypopharynx, and oropharynx. However, combining blood and saliva tests may offer the best chance of finding cancer in any of those regions."

Dr. Agrawal explains that inborn genetic predispositions for most head and neck cancers are rare, but other mutations that don't generally occur in normal cells have long been considered good targets for screening tests. In the case of head and neck cancers associated with human papillomavirus (HPV) Dr. Agrawal and his colleagues searched patients' blood and saliva samples for certain tumor-promoting, HPV-related DNA. For non-HPV-related cancers, which account for the worldwide majority of head and neck tumors, they looked for mutations in cancer-related genes that included TP53, PIK3CA, CDKN2A, FBXW7, HRAS, and NRAS.

The major risk factors for head and neck cancers are alcohol, tobacco, including chewing tobacco, and HPV infection.

For the study, 93 patients with newly diagnosed and recurrent head and neck cancer gave saliva samples, and 47 of them also donated blood samples before their treatment at The Johns Hopkins Hospital and MD Anderson Cancer Center in Texas. The scientists detected tumor DNA in the saliva of 71 of the 93 patients (76%) and in the blood of 41 of the 47 (87%). In the 47 who gave blood and saliva samples, scientists were able to detect tumor DNA in at least one of the body fluids in 45 of them (96%).

When the scientists analyzed how well their tumor DNA tests found cancers in certain regions of the head and neck, they found that saliva tests fared better than blood tests for oral cavity cancers. All 46 oral cavity cancers were correctly identified through saliva tests, compared with 16 of 34 oropharynx cancers (47%), seven of 10 larynx cancers (70%), and two of three hypopharynx cancers (67%).

The oral cavity refers to areas within the mouth, including the lips, front of the tongue, cheeks and gums. The oropharynx and hypopharynx are located in the back of the throat. The larynx, also in the throat, is typically known as the voice box.

"One reason that saliva tests may not have been as effective for cancer sites in the back of the throat is because we didn't ask patients to gargle; we only asked them to rinse their mouths to provide the samples," says Dr. Agrawal, a member of Johns Hopkins' Kimmel Cancer Center and Ludwig Center.

Blood tests correctly identified tumor DNA more often in 20 of 22 oropharynx cancers (91%), six of seven larynx cancers (86%), and all three hypopharynx cancers. Taken together, blood and saliva tests correctly identified all oral cavity, larynx, and hypopharynx cancers and 20 of 22 oropharynx cancers (91%).

Dr. Agrawal points out that the sensitivity of the tests overall depended on the cancer site, stage and HPV status, ranging between 86 to 100%. He also reports that saliva tests performed better for early-stage cancers, finding all 20 cancers, compared with blood tests that correctly identified seven of 10. He and his team found the opposite was true for late-stage cancers: Blood tests found more late-stage cancers (34 of 37), compared with saliva tests (51 of 73). Blood tests also correctly identified HPV-related tumors, occurring in 30 of the 93 patients, more often than saliva tests, probably because HPV-related tumors tend to occur in the back of the throat, which may not have been reached with the saliva rinse.

"Our ultimate goal is to develop better screening tests to find head and neck cancers among the general population and improve how we monitor patients with cancer for recurrence of their disease," says Bert Vogelstein, M.D., the Clayton Professor of Oncology at the Johns Hopkins Kimmel Cancer Center, co-director of the Ludwig Center at Johns Hopkins and a co-author of the study.

The scientists caution that further study of their tumor DNA detection method in larger groups of patients and healthy people is needed before clinical effectiveness can be determined, and that refinements also may be needed in methods of collecting saliva and the range of cancer-specific genes in the gene test panel.

In addition, according to Dr. Agrawal, "We don't yet have definitive data on false positive rates, and won't until there are more studies of the tests in healthy people." However, he notes, the formulas used to analyze their blood and saliva tests are designed to weed out questionable result.

Tuesday, June 23, 2015

Companies say their initial projects will entail developing new automation systems based on PCR and NGS technologies. [iStock/© Chagin]

Hitachi High-Technologies and Qiagen said today they have launched a long-term strategic collaboration to develop molecular testing tools. The value of the collaboration was not disclosed.

The companies said their initial projects will entail developing new automation systems based on polymerase chain reaction (PCR) and next-generation sequencing (NGS) technologies.

The collaboration could be expanded to involve co-commercialization of products in specific geographic markets, Hitachi High-Technologies and Qiagen said, without specifying which markets.

“Developing a co-commercialization collaboration with distribution and customer service in specific geographical regions would be highly accepted by customers of each company,” Yasukuni Koga, head of the medical systems sales and marketing division of Hitachi High-Technologies, said in a statement.

The collaboration is intended to combine Qiagen’s focus on sample technologies, assay technologies, software, and automation solutions with Hitachi High-Technologies’ expertise in industrialized instrument development and manufacturing technologies for life sciences and in vitro diagnostics.

“Combining the NGS-related and other molecular knowhow of Qiagen with the instrumentation expertise of Hitachi High-Technologies will enable us to bring innovative automation solutions to customers all over the world and across the continuum from basic research through to routine molecular diagnostics,” added Thierry Bernard, senior vice president the molecular diagnostics business area at Qiagen and a member of the company’s executive committee.

Tuesday, June 09, 2015

Researchers have developed a technique to visualize the genome much like a mapping app, with the ability to zoom in on individual mutations and zoom out to observe large scale changes. [iStock/ymgerman]

Most of us have used a mapping app at some point, whether for driving directions, finding the best route to the closest subway stop, or just to look at places on the globe we might like to visit one day. The power of these programs is derived from their ability to zoom in on discreet locations within large cities or being able to zoom out to get an overview of how to travel from point A to point B. Imagine now that this was possible for the cancer genome.

Researchers at the University of Wisconsin-Madison are not conceptualizing this technology, as they have developed a new approach that will account for both the discreet locations and a global content of the genome at once. Ultimately, this should enable researchers and clinicians to look at the small- and large-scale genetic changes that define individual cancers.   

"Cancer genomes are complicated but we found that, using an approach like this, you can begin to understand them at every level," stated David Schwartz, Ph.D. professor of genetics and chemistry at the University of Wisconsin-Madison and senior author on the current study.

The findings from this study were published recently in PNAS through an article entitled "Single-molecule analysis reveals widespread structural variation in multiple myeloma."

While the technique and study results are still preliminary, Dr. Schwartz is excited for others to test what he and his colleagues found. Moreover, the results demonstrate the potential of the approach the investigators took, which combines a system called optical mapping with more traditional genomic tools like DNA sequencing

"The approach allows an intimate view of a cancer genome," Dr. Schwartz explained. "You get to see it, you get to measure it, and you get to see it evolve at many levels. This is what we should be doing with every cancer genome and the goal here is to make the system fast enough so this becomes a routine tool."

Specifically, Dr. Schwartz and his team isolated DNA from normal and cancerous tissue from a patient with multiple myeloma at two different stages of the illness: when the cancer was responsive to drug treatment and at a point when it had become resistant to chemotherapy.

First, the researchers performed standard DNA sequencing to obtain the zoomed in portion of the genome. Then DNA was stretched out and placed in a special device. The strands were given specific landmarks and marked with a fluorescent dye. An automated system took images of each of these marked segments, cataloging the molecules, much like a barcode, into large datasets that were then pieced together like a jigsaw puzzle to provide a zoomable view of the genome.   

"It's a rare, near-complete characterization of the complexity of a myeloma genome, from the smallest variance all the way to big chunks of chromosomal material that differ between the tumor DNA and the normal DNA of the patient," stated co-author Fotis Asimakopoulos, M.D., Ph.D., professor of medicine and a multiple myeloma researcher and physician at the UW-Madison School of Medicine and Public Health.

What they found was that across the two time points from when the samples were taken the multiple myeloma genome was marked by an increase in notable mutations and larger scale changes. Not only were there more unusual mutations as the cancer progressed, but whole sections of the genome were removed, flipped around, or even inserted.

"To cure myeloma, we need to understand how genomes evolve with progression and treatment," said Dr. Asimakopoulos. "The more we can understand the drivers in cancer in significant depth, and in each individual, the better we can tailor treatment to each patient's disease biology."

In the meantime, Dr. Schwartz and his team continue to work toward advancing the system making it higher-resolution, more cost-effective and scalable. The researchers would ultimately like to build a system capable of analyzing 1,000 genomes in 24 hours.

Monday, June 08, 2015

Large numbers of people say they want to see their genomic information even when the data are not health-related or are simply raw. [iStock/Dra_Schwartz]

The largest study to date of attitudes towards the use of genomic information shows that the majority of people want access to results from genome sequencing, even if these are not directly related to the condition for which the analysis has been undertaken. This applies even when the data are not health-related or are simply raw, says Anna Middleton, Ph.D., a principal staff scientist at the Wellcome Trust Sanger Institute. She is presenting the results of the survey at the annual conference of the European Society of Human Genetics today in Glasgow.

The survey was aimed at probing the attitudes of the various groups involved in sequencing research, including patients, the public, health professionals, and genomic researchers, towards the types of genomic information they would be interested in receiving. Just under 7,000 people from 75 countries took part in an on-line survey, advertised on social and traditional media, and by an email list-serve.

"We asked participants to imagine that they were taking part in sequencing research with the option to receive personal results, and carefully explained the sorts of results that might come from a sequencing study in ten short films,” she points out. “We found that 98% of participants wanted to know about genes linked to treatable conditions that were serious or life-threatening; they were still interested even if the chance of such a condition occurring was as low as 1%.

According to Dr. Middleton, what was important to them was being forewarned about their future risk of disease so that they could take steps to protect their health. “This makes sense, but we also found that 59% of those surveyed were interested in having access to their own raw data, even though, on its own, it would tell them nothing useful about their future health,” she continues.

Participants perceived a value in raw data that may or may not exist: 'if the scientists know it, I'd like to know it too.' They felt the genomic information simply 'belonged to them' and thus they should be able to have access to it, even if the reality was that they would do nothing with it.

Participants said they also wanted to be connected to the research process. For example, they were keen that genomic researchers should keep re-analyzing their data and report to them if there were new findings. But they also recognized that scientists had an important job to do in doing quality research. The work of answering a particular research question should not be side-tracked by a necessity to supply personalized results. Participants said they were willing to forego the return of individual findings if the delivery of such data compromised the ability of scientists to focus on the answer to a research question.

"It would now be helpful to explore the value that people put on genomic data. For example, would they pay for an interpretation and, if so, how much?" says Dr. Middleton. "Creating clinical-grade health information in a research setting requires funding, resources, and strong clinical connections to the health professionals who will deliver it, explain it, and follow up the patient. This may be out of reach for many researchers. So if research participants expect personalized results, but they also don't want researchers to compromise their research in order to deliver such results, then would they be willing to pay for these services?”

What the team did in its research was explore what people say they might do in a hypothetical situation. What the team plans to do next is explore the actual experience of research participants who are given personal results from sequencing research. The scientists know already that some research participants ask for their raw sequence files and so it would be useful to follow such participants over time to see what they do with these. More also needs to be known about the psychosocial impact of receiving genomic data and whether it has an emotional resonance that people didn't expect.

"Researchers have a responsibility not to harm their research participants, and if they are going to provide results, they need to do this in an ethical way. At the moment our genomics community agrees that if researchers choose to return results that could potentially be clinically actionable these need to be confirmed in a clinically accredited laboratory before they are returned, and there should be a clinician available to share the information with the patient and to provide screening services if necessary,” emphasizes Dr. Middleton. “For research participants who ask for their raw sequence data (that by their very nature, come with no interpretation), then they should be given a clear explanation of the limits of these data together with some signposts to services that they can access for interpretation and support. Without this there is a risk that research participants will turn up at the door of their GP and ask them what it all means.”

Dr. Middleton is a member of the Deciphering Developmental Disorders (DDD) project (www.ddduk.org) after which the DDD study is named. The DDD project is funded by the Health Challenge Fund, a partnership between the Wellcome Trust and the UK Department of Health.

Friday, June 05, 2015

Source: © Robert Mizerek/Fotolia.com

Bio-Techne agreed to acquire 100% ownership of Cliniqa, which specializes in the manufacture and commercialization of quality controls and calibrators as well as bulk reagents used in the clinical diagnostic market.  Its controls and reagents are used in a wide variety of diagnostic tests for such pathologies as cardiac disease diabetes, cancer, immunological disorders, therapeutic drug monitoring, urine analysis and toxicology.

Cliniqa was founded in 1974, is based in San Marcos, CA, and has approximately 75 employees. 

"I am very pleased with this acquisition as it strengthens not only our clinical controls product portfolio, but also our reach into the IVD/clinical diagnostics segment, as well as our management team,” said Charles Kummeth, president and CEO of Bio-Techne. “The addition of Cliniqa adds important capabilities to Bio-Techne as we continue to solidify our market presence and expand our business into key adjacent markets, such as immunodiagnostics."

Cliniqa’s CEO, Kevin Gould, and other members of the Cliniqa leadership team will remain in place following the closing

Friday, June 05, 2015

Scientists at HHMI have developed a screening methodology to basically look back in time in people's sera and see what viruses they have experienced. [iStock/MarkHatfield]

New technology developed by Howard Hughes Medical Institute (HHMI) researchers makes it possible to test for current and past infections with any known human virus by analyzing a single drop of a person's blood. The method, called VirScan, is an efficient alternative to existing diagnostics that test for specific viruses one at a time, according to the scientists.

With VirScan, researchers can run a single test to determine which viruses have infected an individual, rather than limiting their analysis to particular viruses. That unbiased approach could uncover unexpected factors affecting individual patients' health, and also expands opportunities to analyze and compare viral infections in large populations. The analysis reportedly can be performed for about $25 per blood sample.

“We've developed a screening methodology to basically look back in time in people's sera and see what viruses they have experienced,” says Stephen J. Elledge, an HHMI investigator at Brigham and Women's Hospital who led an international team that developed VirScan. “Instead of testing for one individual virus at a time, which is labor intensive, we can assay all of these at once. It's one-stop shopping.”

Dr. Elledge and his colleagues have already used VirScan to screen the blood of 569 people in the U.S., South Africa, Thailand, and Peru. Their study (“Comprehensive serological profiling of human populations using a synthetic human virome”) is described in Science.

VirScan works by screening the blood for antibodies against any of the 206 species of viruses known to infect humans. The immune system produces pathogen-specific antibodies when it encounters a virus for the first time, and it can continue to make those antibodies for years or decades after it clears an infection. That means VirScan not only identifies viral infections that the immune system is actively fighting, but also provides a history of an individual's past infections.

To develop the new test, Elledge and his colleagues synthesized more than 93,000 short pieces of DNA encoding different segments of viral proteins. They introduced those pieces of DNA into bacteriophage. Each bacteriophage manufactured one of the peptides and displayed the peptide on its surface. As a group, the bacteriophage displayed all of the protein sequences found in the more than 1,000 known strains of human viruses.

Antibodies in the blood find their viral targets by recognizing unique features known as epitopes that are embedded in proteins on the virus surface. To perform the VirScan analysis, all of the peptide-displaying bacteriophage are allowed to mingle with a blood sample. Antiviral antibodies in the blood find and bind to their target epitopes within the displayed peptides. The scientists then retrieve the antibodies and wash away everything except for the few bacteriophage that cling to them.

By sequencing the DNA of those bacteriophage, they can identify which viral protein pieces were grabbed onto by antibodies in the blood sample. That tells the scientists which viruses a person's immune system has previously encountered, either through infection or through vaccination. Dr. Elledge estimates it would take about 2–3 days to process 100 samples, assuming sequencing is working optimally. He is optimistic the speed of the assay will increase with further development.

Dr. Elledge says the approach his team has developed is not limited to antiviral antibodies. His own lab is also using it to look for antibodies that attack a body's own tissue in certain autoimmune diseases that are associated with cancer. A similar approach could also be used to screen for antibodies against other types of pathogens.

Thursday, June 04, 2015

© Fotolia/Sebastian Kaulitzk

Exact Sciences and The University of Texas MD Anderson Cancer Center entered an agreement to jointly develop and commercialize blood-based screening and diagnostic tests for the early detection of lung cancer.

The initiative is part of part of MD Anderson's Moon Shots Program and seeks to build upon the center’s research into predictive biomarkers for lung cancer and Exact Sciences’ development and commercialization of Cologuard®, an FDA-approved, noninvasive stool-based DNA colon cancer screening test.

The two groups plan to develop a new blood test that targets biomarkers associated with lung cancer.  The collaboration specifically aims at developing a screening test to determine the need for low-dose computed tomography (LDCT). This test would offer the opportunity to screen nearly 11 million Americans considered high-risk smokers and former smokers, the organizations said.  The partnership is also aimed at developing a diagnostic test to determine the malignant status of nodules found through LDCT screening.

“Taking on lung cancer offers an opportunity to build on the success of Cologuard,” said Exact Sciences’ chairman and CEO Kevin Conroy. “A simple blood test to complement a LDCT scan could significantly improve early-stage lung cancer detection. Our experience working with regulators and insurers coupled with MD Anderson’s world-class research and development capabilities are an ideal match to make a meaningful difference in the war on cancer.”

Tuesday, June 02, 2015

Many more promoter interactions (purple arcs) are captured by the Capture Hi-C method (second track) versus the regular Hi-C method (first track). The interactions from a single promoter (third track) reach numerous other DNA segments, some that are more than one million base pairs apart on the linear sequence.

Sift through metadata. Track contact activity. Identify suspicious patterns. This to-do list sounds as though it were devised by the National Security Agency. But it actually describes a research plan enacted by a group of genomic scientists in Japan and the United Kingdom.

The scientists sifted through a catalogue of gene-promoter interactions, tracked promoters associated with known mutations, and identified potential “bad actors.” In this case, the suspects had nothing to do with threats to national security. Instead, they were thought to instigate disease processes, specifically, inflammatory bowel disorders such as Crohn’s disease.

The scientists used technology that advances genomic surveillance as dramatically as computer networking has advanced intelligence operations, which long ago progressed from the selective planting of “bugs” and phone line “taps.” In fact, the scientists themselves likened their work to the collection and analysis of telephony metadata.

For the rest of the story, click here.

Tuesday, June 02, 2015

A single biomarker plus a fixed threshold may equal a missed diagnosis—actually, a great many missed diagnoses. But fixed thresholds aren’t inevitable. For example, a serum biomarker used to screen women for ovarian cancer can yield more accurate results if it is assessed serially. This biomarker, called cancer antigen 125 (CA125), can detect cancer in 86% of women with invasive epithelial ovarian cancer (iEOC)—provided the pattern of CA125 concentration changes over time is assessed. If, however, CA125 figures in a simplistic “less than/greater than” metric, screen-detected cancers are just 41% or 48%, according to data from clinical trials or clinical practice, respectively.

For the rest of the story, click here.

Tuesday, June 02, 2015

Novel advances in personalized and precision medicine (PPM) could offer enormous gains in healthy life expectancy for Americans, but the incentives to develop them are weak, according to Victor Dzau, M.D., President of the U.S. Institute of Medicine. He and colleagues discussed PPM in an article (“New developments in personalized medicine could save billions of dollars in improved health”) in The Lancet.

PPM tailors medical treatment to the individual characteristics of each patient, according to their susceptibility to a particular illness. But PPM goes beyond just targeting therapies at individuals who are ill; it includes the ability to identify those at highest risk of developing a disease, and who would benefit most from prevention measures.

For the rest of the story, click here.

Tuesday, June 02, 2015

Source: iStock/YinYang

A European Journal Human Genetics survey of nearly 7,000 people from 75 countries has revealed that 98% want to be informed if researchers using their genetic data stumble upon indicators of a serious preventable or treatable disease. The study, which comes after the U.K. government’s announcement that Genomics England will sequence 100,000 genomes by 2017, begins an important and ongoing conversation about how our genomic data is used.

The results show that genomic data has a perceived value to participants even if it is not currently clear what the information means for health outcomes. However, in general, the majority of people were interested in clinically actionable data and genetic professionals surveyed were concerned about returning data that cannot yet be interpreted accurately.

“The advent of fast, efficient genetic sequencing has transformed medical research over the past decade and it’s set to revolutionize clinical care in the future,” says Anna Middleton, Ph.D., first author from the Wellcome Trust Sanger Institute. “Policy surrounding the use of genetic data in research and clinical settings must be directed by the views and experiences of the public, patients, clinicians, genetic health professions, and genomic researchers. This study represents a first step in informing people of the issues and gathering their responses.”

For the rest of the story, click here.

Tuesday, June 02, 2015

[Courtesy of the National Cancer Institute]

CHICAGO—Clinical investigators from the National Cancer Institute (NCI) announced today at the annual meeting of the American Society of Clinical Oncology (ASCO) that they will begin open patient enrollment in July for the much anticipated Molecular Analysis for Therapy Choice (MATCH) precision medicine trial.

The Phase II study will seek to determine if targeted drug therapies for cancers with specific mutational backgrounds will be effective, regardless of the specific cancer type. NCI-MATCH will employ 20 different study drugs or drug combinations each of which targets a specific gene mutation—with the intent to match each patient with a specific therapy that targets the molecular mutation specific to their tumor. The study was co-developed by NCI and the ECOG-ACRIN Cancer Research Group, which is part of the NCI-sponsored National Clinical Trials Network (NCTN) and is spearheading the project.  

The clinical trials will contain a number of substudies for each treatment being investigated, opening with 10 and quickly progressing to 20 substudies within a few months. The first 10 studies will be disseminated through 2,400 participating sites across the US.

“NCI-MATCH is a unique, ground-breaking trial,” said NCI’s acting director Doug Lowy, M.D. "It is the first study in oncology that incorporates all of the tenets of precision medicine. There are no other cancer clinical trials of this size and scope that truly bring the promise of targeted treatment to patients whose cancers have specific genetic abnormalities. It holds the potential to transform cancer care.”

There are two main enrollment steps for patients to be considered eligible for the trial. Each patient will initially be enrolled for genetic screening, in which samples of their tumor will be biopsied and undergo DNA sequencing. This step is for the detection of genetic abnormalities that may be driving tumor growth and if that tumor can be targeted by one of a wide range of drugs being studied. If a molecular abnormality is detected, for which there is a specific substudy available, patients will be further evaluated to determine if they meet the precise eligibility requirements within that arm to be accepted in NCI-MATCH.

This targeted sequencing approach, distinguished by its very low sample requirement and fast turnaround time, will rely on Life Technologies’ Ion Torrent next generation sequencing platform, which can accurately and reliably sequence across a large range of tumor sample types.

“A study of this scale would not be feasible using the traditional one-sample, one-biomarker testing approach,” stated Mark Stevenson, executive vice president and president, Life Sciences Solutions, for Thermo Fisher.

 While discussing the criteria for choosing the appropriate sequencing platform for the NCI-MATCH trial Stanley Hamilton, M.D., head of pathology and laboratory medicine at the MD Anderson Cancer Center and ECOG-ACRIN laboratory stated that “clinical trials of this size and type must rely on technology that can accurately detect a wide range of infrequent gene alterations with a single assay of small amounts of DNA and cDNA from a formalin-fixed paraffin-embedded biopsy specimen or fine needle aspiration specimen.” Dr. Hamilton continued that “meeting these requirements was a key deciding factor for choosing this platform after we completed our evaluation process.”

The NCI-Match study will seek to identify one of the 143 genes associated with cancer that can be targeted by the compounds use in the trial. For quality control all biopsy samples will be sent to one location for processing: the ECOG-ACRIN Central Biorepository and Pathology Facility at the University of Texas MD Anderson Cancer Center in Houston, with DNA analysis being performed at one of four facilities across the US.

"The use of a unique kit for specimen collection, shipment, and centralized tissue processing, assures high-quality analysis,” stated Stanley Hamilton, M.D., head of pathology and laboratory medicine at the MD Anderson Cancer Center and ECOG-ACRIN laboratory lead. “The network of four molecular diagnostics labs provides capacity for large numbers of patients to be screened in the trial. Pilot testing of specimens across the four locations showed remarkable reproducibility of the molecular results—another important aspect of quality assurance in trials of this scope and scale."

There are two main clinical endpoints that investigators are looking to gauge in the NCI-MATCH trial. The primary endpoint is the overall response rate, which is the proportion of patients in the trial whose tumors shrink by a predefined amount over a specific time period. The secondary endpoint is 6-month progression-free survival time, which is a measure a patient’s disease stability.

“For our purposes, a response rate of 5 percent or less in a molecularly-defined population will not be considered promising, whereas a response rate of 16 percent to 25 percent will be encouraging,” said Barbara Conley, M.D., associate director of the NCI’s Cancer Diagnosis Program and NCI study co-chair. “After starting treatment in NCI-MATCH, a 6-month progression-free survival of 15 percent will not be considered promising, whereas a progression-free survival at six months of 35 percent will indicate that we would want to develop that treatment further.”

To view the NCI-Match Clinical Trial infographic click here.

Andy Webb

Monday, June 01, 2015

EKF’s PointMan works by enriching the DNA sample for the point-mutated sequence, using a simple reagent set that combines with standard DNA extracts and runs on a real-time thermal-cycle platform.

The initial diagnosis of cancer is usually based on taking a physical biopsy and then a skilled interpretation by a pathologist followed by tumor genome sequencing to generate informed treatment decisions. 

Numerous genomic targets have been utilized as diagnostic markers for treatment with specific therapeutics. Indeed several anticancer therapies require that pharmacogenomic information is obtained before treatment can be initiated. Diagnostic tests that have established this new standard of care include ER and HER2 in breast cancer, BCR-ABL in chronic myeloid leukemia, c-Kit in gastrointestinal stromal tumors, BRAF in melanoma, KRAS in colorectal cancer, and EGFR and ALK in lung cancers.

With increasing development of targeted therapeutic agents in oncology comes a corresponding need for personalized treatment strategies. These strategies will facilitate the selection of patients who are most likely to benefit from a particular therapy, while simultaneously avoiding the cost and morbidity of futile interventions.

For the rest of the story, click here.


Jeffrey S. Buguliskis, Ph.D.

Monday, June 01, 2015

A classic example of applying pharmacogenomics in a clinical setting. A blood sample is taken from patients with the same condition and either added to a microarray or used with next-generation sequencing to look for genetic variants that affect responses to drugs used to treat the condition. The analysis will yield results that allow physicians to determine if their patient will have a positive response to the drug treatment. [National Human Genome Research Institute]

One of the most practical applications of precision medicine lies within the field of pharmacogenomics, a portmanteau of pharmacology and genomics. It is a discipline designed for tailoring drug treatments to an individual’s genetic make-up.

While scientists have had clinically relevant pharmacogenetic examples of drugs functioning only for patients with specific genetic backgrounds for several decades, the field has burgeoned into the encompassing specialty of pharmacogenomics, shifting away from observing a small number of candidate genes to searching for genome wide biomarkers.

Interestingly, one of the first examples of pharmacogenetics occurred around 510 BCE, when the Greek philosopher and mathematician Pythagoras observed that the ingestion of fava beans were fatal to some individuals and not to others. What Pythagoras couldn’t do at the time was formulate a scientific hypothesis to provide him with an answer as to what had caused such a disparity in symptoms. Now we know about the disease clinicians often refer to as favism, which is a genetic mutation in the glucose-6-phosphate dehydrogenase gene that predisposes those with the mutation to potentially fatal hemolytic anemia in the presence of certain foods, drugs, or chemicals. 

For the rest of the story, click here.


Wendy Whittington, M.D.

Monday, June 01, 2015

Personalized medicine—arguably a more encompassing set of practices than precision medicine—is poised to benefit individual patients, particularly in the context of shared decision making. [Fotolia/Alexander Raths]

There is much enthusiasm these days around precision medicine, and it’s very exciting to see effective individualized care delivered to patients based on their genomic information. I can’t understate the importance of giving the best care possible and avoiding potentially toxic treatments for patients by knowing that a particular medication may or may not be effective for that individual. This science is growing rapidly and many patients stand to benefit from it.

Think of the exponential benefits we might see if we were to layer a personalized element onto this young but already successful field. If my patient’s genomic make up is such that drug X is the scientifically obvious choice to shrink her tumor, but drug X needs to be taken in a precise fashion that will never work with my patient’s lifestyle and diet, then I have more work to do. 

Wouldn’t it be powerful if we could layer lifestyle and other factors on top of our scientific knowledge to really get it right? That’s the idea behind shared decision making, in which patients and their doctors together weigh the pros and cons of treatments and craft plans of care that meet the individual needs of each patient. As we amass medical data, our understanding grows of how patients’ outcomes are affected by various treatments. Combining this knowledge with genomic data and individual patient preferences holds great promise for better outcomes.

For the rest of the story, click here.

MaryAnn Labant

Monday, June 01, 2015

Families can be started in both traditional and nontraditional ways; preconception carrier screening provides the information needed for prospective parents to figure out their preferred direction before conception. [iStock/alynst]

Earlier this year, the Obama Administration launched the Precision Medicine Initiative with a $215 million investment in the President’s 2016 Budget. Heralded as a bold new research effort to revolutionize how we improve health and treat disease, the Precision Medicine Initiative is intended to pioneer a new model of patient-powered research to accelerate biomedical discoveries and provide clinicians with new tools, knowledge, and therapies.

Supporting the concept of precision medicine, preconception carrier screening predicts the chances of having a child with specific genetic disorders while diagnostic testing determines the cause of pediatric-onset and other genetic disorders.

Families can be started in both traditional and nontraditional ways; preconception carrier screening provides the information needed for prospective parents to figure out their preferred direction before conception. Counsyl provides screening for diseases where advanced knowledge makes a difference in health outcomes, whether it is changing a behavior, pursuing preventive measures, or simply preparing for what lies ahead.

For the rest of the story, click here.

Monday, June 01, 2015

© auremar - Fotolia.com

Eurofins Scientific, a provider of bio-analytical testing and genomic services, signed an agreement to acquire Diatherix Laboratories for approximately $50 million, plus an earn-out upon achievement of predefined revenue and profitability targets.

Diatherix employs around 100, serves close to 7,000 healthcare providers across the U.S., and expects to generate revenues of about $40 million in 2015. Eurofins said Diatherix strengthens its growing footprint in the specialty clinical diagnostics market. Based in Huntsville, Alabama, Diatherix offers molecular diagnostic testing services to hospitals and physicians using TEM-PCR™ (target enriched multiplex PCR) technology for detection of infectious diseases.

According to Diatherix, TEM-PCR is a molecular multiplex technology that allows rapid DNA/RNA identification of multiple pathogens in a single sample and specific genetic drug resistance diagnostic, in six hours. Diatherix said it has developed several diagnostic panels to identify multiple organisms in samples quickly and accurately, helping physicians and healthcare providers choose more effective antimicrobial therapy and improve patient outcomes.

Eurofins said Diatherix’ service offering and expertise complement its acquisition of ViraCor in May 2014 for approximately $255 million. ViraCor provides biologic and large molecular biomarker support, along with molecular testing to hospitals, physicians, and biotech and pharmaceutical companies.

"This acquisition reflects our strategy of expanding and strengthening our network of competence centers,” said Gilles Martin, M.D., Eurofins CEO. “Diatherix strengthens Eurofins' growing footprint in the specialty clinical diagnostics market, with truly unique and innovative services with high positive impact for patient care. In combination with ViraCor and Boston Heart, Diatherix reinforces the group's position in genetic testing to better serve the global healthcare community."

Monday, June 01, 2015

The June issue of Clinical OMICs is available now! Check it out by clicking on the link below.

Clinical OMICs Volume 2, Issue No. 6

Wednesday, May 27, 2015

Source: iStock/© Squaredpixels

Halozyme Therapeutics said today it will co-develop a companion diagnostic for its cancer drug candidate PEGPH20 with Ventana Medical Systems, a member of the Roche Group. The value of the collaboration was not disclosed.

Ventana will ultimately commercialize the in vitro diagnostic, an assay designed to identify high levels of hyaluronan (HA), a chain of natural sugars distributed throughout human tissue that can accumulate around cancer cells. 

The diagnostic—which will use Haolzyme’s HA binding protein—is being developed as the company prepares to launch a global Phase III trial next year to assess a combination of its PEGPH20 with Abraxane® (nab-paclitaxel) and gemcitabine in metastatic pancreatic cancer patients with high HA levels.

PEGPH20 is an investigational PEGylated form of Halozyme's recombinant human hyaluronidase or rHuPH20. PEGPH20 is under clinical development for systemic treatment of tumors that accumulate HA.

The FDA has granted fast track status for the compound in combination with gemcitabine and nab-paclitaxel for metastatic pancreatic cancer, while the agency and the European Commission have both given PEGPH20 their orphan drug designations for pancreatic cancer.

“The agreement is an important milestone in our PEGPH20 program as we study the potential of PEGPH20 across multiple tumor types,” Halozyme president and CEO Helen Torley, M.B., Ch.B., said in a statement.

Added Doug Ward, vp with Ventana Companion Diagnostics: “The PEGPH20 program, coupled with our global reach, has the potential to improve the standard of care in pancreatic cancer for patients around the world.”

Ventana has agreed to pursue regulatory approvals for the diagnostic in Europe, the U.S., and other countries.

The pharma giant is also developing and commercializing combinations of Roche target compounds with Halozyme’s rHuPH20 using Halozyme’s ENHANZE™ drug delivery technology platform under an exclusive license granted in 2006 that was valued at more than $601 million plus royalties for Halozyme.

Roche now has rights to apply the technology to up to eight targets, including Roche’s marketed drugs Herceptin® and MabThera.® The European Commission has approved subcutaneous formulations of both drugs that use ENHANZE.

Halozyme is also using ENHANZE to develop drugs under collaborations with Baxter International, Johnson & Johnson’s Janssen Biotech, and Pfizer.

Wednesday, May 27, 2015

Biocartis and Fast-track diagnostics are developing a multiplex respiratory panel for detecting viral and bacterial targets in upper respiratory tract infections. [iStock/Pictore]

Biocartis and Fast-track diagnostics, which provides multiplex polymerase chain reaction (PCR) test kits for infectious disease, entered into a strategic collaboration to develop a range of multiplex infectious disease tests to run on the Biocartis Idylla™ molecular diagnostics (MDx) system.

Biocartis and Fast-track diagnostics plan to use a new approach to infectious disease diagnostics called “syndromic multiplex testing,” which should enable the identification of a broader range of disease pathogens in a single test. Most current methods focus on the detection of one or a few pathogens expected to be present in a patient sample. If the sample is negative, a new test will be performed for other pathogens, increasing the time to result. With syndromic multiplex tests, the initial test will not just look for the most likely pathogen, but also for a range of less likely pathogens, preventing the need to retest.

As part of the collaboration, tests from Fast-track diagnostics’ infectious disease menu will be developed for use on the Idylla fully automated platform.

The first assay to be developed under the collaboration is a multiplex respiratory panel for the detection of viral and bacterial targets in upper respiratory tract infections.

Tuesday, May 26, 2015

Source: iStock/© goldi

Averages shout, and individuals whisper. That, in a nutshell, is the frustration of single-cell transcriptomics. Although innumerable cell types have unique gene-expression profiles, they are hard to discern. Great, thundering herds of cells typically give up their RNA to be sequenced all in one batch. It is possible to effectively cut cells from the herd with a technique called RNA-seq, which enables RNA sequencing with single-cell resolution. Still, RNA-seq does not provide an effective way to routinely isolate and process large numbers of individual cells for quantitative in-depth sequencing.

This limitation, however, may soon be lifted. According to two teams of scientists at Harvard Medical School, microfluidics can be combined with genetic barcoding to bring about high-throughput single-cell transcriptomics. One team, in the laboratory of Steven McCarroll, developed a technique called Drop-seq. The other team, in the laboratory of Marc Kirschner, developed a technique called inDrops.

Both methods use microfluidic devices to co-encapsulate cells in nanometer-sized water droplets along with genetic-barcoding beads. The droplets get created in a tiny assembly line, streaming along a channel the width of a human hair. The bead barcodes get attached to the genes in each cell, so that scientists can sequence the genes all in one batch and still trace each gene back to the cell it came from.

The McCarroll and Kirschner labs were able to advance work initiated by the researchers Evan Macosko and Allon Klein, respectively. Macosko and Klein make their beads in different ways. The droplets get broken up at different steps in the process. Other aspects of the chemistry diverge. But the result is the same.

After running a single batch of cells through Drop-seq or inDrops, scientists "can see which genes are expressed in the entire sample--and can sort by each individual cell," said Klein. They can then use computer software to uncover patterns in the mix, including which cells have similar gene expression profiles. That provides a way to classify what cell types were in the original tissue—and to possibly discover new ones.

Current methods allow researchers to generate 96 single-cell expression profiles in a day for several thousand dollars. Drop-seq, by comparison, enables 10,000 profiles a day for 6.5 cents each.

"If you're a biologist with an interesting question in mind, this approach could shine a light on the problem without bankrupting you," said Macosko. "It finally makes gene expression profiling on a cell-by-cell level tractable and accessible. I think it's something biologists in a lot of fields will want to use."

Both teams published their work May 21 in the journal Cell. The McCarroll team published an article entitled, “Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets.” The Kirshner team published an article entitled, “Droplet Barcoding for Single-Cell Transcriptomics Applied to Embryonic Stem Cells.”

“We analyzed transcriptomes from 44,808 mouse retinal cells and identified 39 transcriptionally distinct cell populations, creating a molecular atlas of gene expression for known retinal cell classes and novel candidate cell subtypes,” wrote the McCarroll team. “Drop-seq will accelerate biological discovery by enabling routine transcriptional profiling at single-cell resolution.”

“The [inDrops] method shows a surprisingly low noise profile and is readily adaptable to other sequencing-based assays,” wrote the Kirschner team. “We analyzed mouse embryonic stem cells, revealing in detail the population structure and the heterogeneous onset of differentiation after leukemia inhibitory factor (LIF) withdrawal.”

McCarroll, Macosko, and their colleagues are excited to explore the brain with Drop-seq. With luck, that will include discovering new cell types, constructing a global architecture of those cell types in the brain and understanding brain development and function as they relate to disease.

Among the questions they want to pursue are: What are all the cell types that make the brain work? How do these cell types vary in their functions and responses to stimuli? What cell populations are missing or malfunctioning in schizophrenia, autism and other disorders of the brain?

Kirschner, Klein, and their colleagues, meanwhile, are keenly interested in other areas, including stem cell development. "Does a population of cells that we initially think is uniform actually have some substructure?" Klein wants to know; he's trying to find out by studying immune cells and different kinds of adult stem cells. "What is the nature of an early developing stem cell? What endows those cells with a pluripotent state? Is gene expression more plastic or does it have a well-defined state that's different from a more mature cell? How is its fate determined?"

Using inDrops, Klein and team have confirmed prior findings that suggest even embryonic stem cells are not uniform. They found previously undiscovered cell types in the population they studied, as well as cells in intermediate stages that they suspect are converting from one type to another.

Although both teams are excited by the massive amounts of data they and other researchers will obtain from Drop-seq and inDrops, they realize the sheer volume of information poses a problem as well. "We have thousands of cells expressing tens of thousands of genes. We can't look in 20,000 directions to pick out interesting features," explained Klein.

Machine learning is able to do some of that, and the teams have already employed new statistical techniques. Still, Kirschner has called on mathematicians and computer scientists to develop new ideas about how to analyze and extract useful information about our biology from the mountains of data that are on the horizon.

Thursday, May 21, 2015

Scientists create comprehensive genetic map for advanced prostate cancer and find an array of clinically actionable targets. [Judith Glick Ehrenthal/iStock]

Based on the most current data, approximately 14% of men will be diagnosed with prostate cancer at some point during their lifetime. If detected early, long term clinical prognosis is very good, however in many cases, prostate cancer can become metastatic and drug resistant tumor rates are on the rise. 

Now, a new study led by scientists at The Institute of Cancer Research (ICR) in London created a comprehensive map of genetic mutations within lethal forms of metastatic prostate cancer. What’s being hailed as the diseases’ Rosetta Stone, found that nearly 90% of men with advanced prostate cancer carry genetic mutations that can be targeted by either existing or new cancer drugs.  

“We have for the first time produced a comprehensive genetic map of the mutations in prostate cancers that have spread round the body,” explained co-author Johann de Bono, M.D., Ph.D., professor of experimental cancer medicine at ICR. “This map will guide our future treatment and trials for this group of different lethal diseases. We’re describing this study as prostate cancer’s Rosetta stone—because of the ability it gives us to decode the complexity of the disease, and to translate the results into personalized treatment plans for patients.

The findings from this study were released today in Cell through an article entitled “Integrative Clinical Genomics of Advanced Prostate Cancer.”

The investigators believe that physicians could begin testing for these clinically actionable markers and give patients with advanced prostate cancer existing drugs or drug combinations targeted at these genomic aberrations within their tumors.

The ICR researchers and their collaborators isolated samples form 150 patients with advanced prostate cancer and analyzed the genetic code from metastatic tumors within their lymph nodes, liver, soft tissues, and bone.

Interestingly, the researchers found that nearly two thirds of the patients had mutations in a molecule that interacts with the male hormone androgen, which is targeted by current standard treatments—possibly leading to new therapies for hormone therapy.  

“Our study shines new light on the genetic complexity of prostate cancer as it develops and spreads—revealing it to be not a single disease, but many diseases each driven by their own set of mutations,” said Dr. de Bono. “What’s hugely encouraging is that many of the key mutations we have identified are ones targeted by existing cancer drugs—meaning that we could be entering a new era of personalized cancer treatment.”

Additionally, the study found mutations in the BRCA1 and BRCA2 genes, which have been successfully treated using PARP inhibitors for breast cancer patients. Moreover, the researchers discovered new mutations that had never been detected before in the PI3K and RAF gene families, which could be targeted by existing chemotherapeutic drugs.    

The ICR scientists also found a small percentage of the patients were born with DNA errors that predisposed them to prostate cancer—strengthen the case for genetic screening for people with a family history of the disease.

“Cancer becomes lethal at the stage when it spreads round the body and stops responding to treatment—but until now it has been incredibly difficult to find out exactly what is going on genetically at that critical point” said Paul Workman, Ph.D., chief executive and president of ICR. “This major new study opens up the black box of metastatic cancer, and has found inside a wealth of genetic information that I believe will change the way we think about and treat advanced disease.”

Monday, May 18, 2015

According to new draft guidelines, BRCA1 and BRCA2 genetic tests will not be covered unless they have undergone a technical assessment and been received favorably by the Molecular Diagnostics Services Program. [Tyler Olson/Fotolia]

The Centers for Medicare & Medicaid Services (CMS) has issued a draft local coverage determination (LCD) allowing limited coverage for BRCA1 and BRCA2 genetic testing, both individually and as part of multi-gene panels.

According to the draft, BRCA tests will not be covered unless they have undergone a technical assessment and been received favorably by the Molecular Diagnostics Services (MolDx) Program by Palmeto GBA, a Medicare administrative contractor. Even then, the tests will be covered only for patients meeting any of four circumstances:

  • A personal history of female breast cancer and any of 11 indications pertaining to age of diagnosis, family history, and type of cancer.
  • A personal history of other forms of cancer.
  • A family history of cancer.
  • Known familial mutation.

Additionally, BRCA1 and BRCA2 genetic testing for breast or ovarian cancer susceptibility with multi-gene next-gen sequencing panels is covered as medically necessary for patients who meet all four criteria: Pre-test genetic counseling independent of the lab has been performed; post-test independent counseling is planned; all genes in the panel are “relevant” to a patient’s personal and family history; patient also meets criteria for at least one other hereditary cancer syndrome, including but not limited to Li-Fraumeni syndrome, Cowden syndrome, or Lynch syndrome.

“Testing with a targeted panel may be indicated as a cost effective strategy when the individual’s symptoms or family history meet testing criteria for more than one hereditary cancer syndrome. All genes included in the test should be relevant to the personal and family history for the individual being tested,” the draft LCD stated.

The draft LCD declared that CMS will only cover BRCA1 and BRCA2 screening for breast or ovarian cancer once in a lifetime—and not for people who are carrying out genetic screening in the general population, people with no personal history of breast or ovarian cancer outside of covered indications, or women younger than age 18.

“If a patient has been previously tested for BRCA1 and BRCA2, repeat testing prior to Lynparza therapy is not reasonable and necessary and will not be covered by Medicare,” the draft added.

Lynparza (olaparib) is the AstraZeneca poly(ADP-ribose) polymerase (PARP) inhibitor approved by the FDA last year against cancer. Lynparza is indicated as a monotherapy in patients with ovarian cancer and with deleterious or suspected deleterious germline BRCA1or BRCA2 mutation, who have been treated with three or more prior lines of chemotherapy.

CMS’ draft also noted that the Patient Protection and Affordable Care Act or “Obamacare” requires private group and individual health plans to cover genetic counseling and, if appropriate, genetic testing for women at risk for hereditary breast and ovarian cancer syndrome as a preventive service with no out­-of­-pocket expense.

The draft LCD will be discussed at the combined meeting of the Kentucky and Ohio Carrier Advisory Committees (CACs), set for June 16. The following day, CMS will begin accepting comment on the draft LCD, through August 3.

Thursday, May 14, 2015

Source: © vishnukumar/Fotolia.com

Human Longevity (HLI) and the Cleveland Clinic agreed to collaborate to sequence and analyze blood samples from Cleveland Clinic's GeneBank study of de-identified patients. The two organizations will apply whole genome, cancer, and microbiome sequencing focusing on a subset of samples with the goal of discovering novel disease genes and disease pathways associated with heart disease.

"Cleveland Clinic is one of the premier clinical health care settings in the world and we are excited to be working with Dr. Cosgrove and his team. Using HLI's powerful genomic technologies and analysis tools to better understand the biological basis for disease should enable earlier intervention and better treatments," said J. Craig Venter, Ph.D., CEO of HLI.

"In medicine we are constantly exploring opportunities to better understand how diseases develop and what we can do to either prevent or provide the most impactful and effective course of treatment," said Toby Cosgrove, M.D., president and CEO of Cleveland Clinic. "We are thrilled to be advancing the correlation of genomic data with clinical care."

HLI is currently sequencing and analyzing thousands of whole genomes per month. The company is integrating this whole genome sequence data with clinical measures and imaging within the HLI Knowledgebase™, which includes the company's proprietary informatics analysis and data interpretation and integration system.

Wednesday, May 13, 2015

Source: istock/© monkeybusinessimages

The Montreal Heart Institute (MHI) agreed to collaborate with AstraZeneca to search the genomes of up to 80,000 patients for genes associated with cardiovascular diseases and diabetes, their complications, and treatment outcomes. The goal is to drive understanding of the biologic mechanisms underlying these conditions and their complications and to uncover which genetic traits are linked to better treatment outcomes.

MHI will genotype up to 80,000 DNA samples from AstraZeneca's biobank. The samples include both tissue and blood samples which have been collected over a period of 12 years under informed consent from patients who have entered clinical trials to test cardiovascular or diabetes treatments.

MHI's Beaulieu-Saucier Pharmacogenomics Centre will initially use an approach called genome-wide SNP analysis to identify regions of DNA that predispose to, or cause, cardiovascular diseases and diabetes or are associated with responses to treatments. They will then apply other technologies, such as next generation sequencing, to carry out full gene sequencing of areas of interest to identify new genes associated with disease, with disease complications such as heart attacks, strokes, diabetic nephropathy, or retinopathy, and with treatment outcomes in terms of responsiveness to medication.

The knowledge gained from genotyping the samples will be applied to the development of new medicines tailored to treat subsets of patients with particular genetic profiles, according to officials at AstraZeneca. The information will also enable a personalized healthcare approach to the use of existing treatments, which means using specific medicines to treat the patient populations which are most likely to respond, noted Ruth March, vp, personalized healthcare & biomarkers at AstraZeneca.

“This partnership has the potential to deliver an unprecedented amount of clinical and scientific information about cardiovascular diseases and diabetes. We expect to identify genes that are associated with more severe forms of disease, and those that are associated with treatment outcome,” continued March. “The information will help us to develop new medicines for these conditions and to target them to the patients who respond best using biomarkers and companion diagnostic tests. We're delighted to be working with the Montreal Heart Institute who has the expertise and technological know-how to deliver such a transformational program. Together we are taking personalized healthcare beyond its great heritage in oncology to benefit patients with cardiovascular disease and diabetes."

Monday, May 04, 2015

Source: © Robert Mizerek/Fotolia.com

Agilent Technologies agreed to acquire Cartagenia, which provides software and services for clinical genetics and molecular pathology labs. Cartagenia, which has offices in Leuven, Belgium, and Boston,  provides software solutions for variant assessment and reporting of clinical genomics data from next-generation sequencing and microarrays. Uniquely geared to routine clinical labs

Cartagenia's solutions are FDA-registered as exempt Class I Medical Devices in the U.S. and as Class I Medical Devices in Europe. The Cartagenia Bench platform enables technicians, lab directors, and clinicians to visualize, assess, and report clinical genetics data in the context of patient information.

With Cartagenia Bench, labs can build an internal knowledge base, build variant assessment SOPs, automate report drafting, and access a wide range of community-validated, private and premium content resources, whether for oncology or inherited disease, according to Agilent officials.

Cartagenia's platform also provides support for consortia of collaborating labs. Data-sharing has become an essential requirement for the community, and through private and public consortia, users can connect and pool their knowledge on rare diseases and actionable findings.

"Cartagenia's approach to enabling the interpretation of clinical genomics data is revolutionary," said Jacob Thaysen, president of Agilent's diagnostics and genomics group. "We look forward to providing Cartagenia's software solutions to our clinical genetics and molecular oncology customers and to providing Cartagenia's existing customers with access to our global service and support network. Together, Agilent and Cartagenia can help remove bottlenecks inherent in analysis, interpretation and reporting clinical data-resulting in faster answers for patients."

The acquisition is expected to be completed May 19., subject to local laws and regulations and customary closing conditions. Cartagenia employs 36 people, all of whom will be offered employment with Agilent.

Financial terms of the transaction were not disclosed.

About Cartagenia

Cartagenia supplies variant assessment support and lab report automation software, database systems, and related services to genetic labs, pathology labs and clinicians, enabling them to perform clinically relevant genetic analyses quickly and efficiently, and offer patients and careers high-quality genetic interpretation and counseling.

Cartagenia Bench Lab allows automation of variant assessment protocols and lab report generation for structural and molecular variant assays such as Arrays, Sanger and Next Generation Sequencing. It supports communication with referring physicians, allows labs and clinicians to put variants in their clinical context, and supports confident data sharing.

The Cartagenia Bench platform is built in collaboration with genetics labs and clinical experts involved in routine medical practice. Because of this, Bench Lab addresses the specific needs of genetic diagnostic labs and clinicians.

Cartagenia Bench is built using a certified ISO13485 Quality Management System and is registered with the FDA as an exempt Class I Medical Device in the United States and as a Class I Medical Device in Europe in conformity with the essential requirements and provisions of the Council Directive 93/42/EEC.

Monday, May 04, 2015

Source: iStock/ktsimage

Scientists at the University of North Carolina School of Medicine and UNC Lineberger Comprehensive Cancer Center say they have developed a technique for finding where DNA repair happens throughout all of human DNA. Their study (“Genome-wide analysis of human global and transcription-coupled excision repair of UV damage at single-nucleotide resolution”), published in Genes & Development, offers scientists a potential way to find and target the proteins cancer cells use to circumnavigate therapy, according to the researchers, who add that the benefit of this new method could be more effective and better tolerated classes of cancer therapeutics.

The research, led by Aziz Sancar, M.D., Ph.D., the Sarah Graham Kenan professor of biochemistry and biophysics, reportedly marks the first time scientists have been able to map the repair of DNA damage over the entire human genome.

"Now we can say to a fellow scientist, 'tell us the gene you're interested in or any spot on the genome, and we'll tell you how it is repaired,'" said Dr. Sancar, co-senior author and member of the UNC Lineberger Comprehensive Cancer Center. "Out of six billion base pairs, pick out a spot and we'll tell you how it is repaired."

When DNA is damaged, cells use many enzymes to cut the strand of DNA and excise the damaged fragment. Then, other enzymes repair the original DNA so that the cells can function properly. Previously, Dr. Sancar's lab relied on purified enzymes to discover how this process happens in DNA damaged by UV irradiation and by chemotherapeutic drugs such as cisplatin and oxaliplatin.

In recent years, Michael Kemp, Ph.D., a researcher on Dr. Sancar's team, found that a particular protein called TFIIH bound tightly to the excised damaged DNA fragment in the test tube. But for this information to be truly useful to biomedical researchers, the experiment needed to be replicated in human cells.

Extracting a stable TFIIH-DNA fragment proved difficult. Not until postdoctoral fellow Jinchuan Hu, Ph.D., joined Dr. Sancar's lab could the team accomplish the task.

Through a series of sophisticated experiments with human skin cells, Dr. Hu exposed the cells to UV radiation and used an antibody against the enzyme TFIIH to isolate the enzyme complex with the excised DNA damage. Then he created experimental techniques to pull the enzyme, as well as the excised DNA fragment it was bound to, from the cells.

The fragment was stable enough for Dr. Sancar's lab to sequence it. Then, Sheera Adar, Ph.D., fellow postdoc, and Jason Lieb, Ph.D., co-senior investigator of the study used their expertise in computational biology to analyze where the DNA repair happened throughout the entire genome and thus generate a human genome repair map for the first time.

Because UV radiation and common chemotherapy drugs such as cisplatin cause DNA damage in similar ways, Dr. Sancar's team is now using their new DNA excision repair method, known as XR-Seq, to study cells affected by cisplatin. They also hope to use it to study the biochemical reactions in animal models with the goal of finding the specific mechanisms that allow cancer cells to repair DNA damage to survive.

“XR-seq and the resulting repair maps will facilitate studies of the effects of genomic location, chromatin context, transcription, and replication on DNA repair in human cells,” wrote the investigators.

"Cisplatin is an old drug," said Dr. Adar. "Right now, it's used with other drugs as a combination therapy. We know these drugs make cancer cells more sensitive to cisplatin. But we don't really know how they do this. We now have an assay to find out how the cells' DNA is being repaired. Our goal is to make cancer cells even more sensitive to existing drugs to help patients."

The research also revealed that parts of the genome scientists previously thought did very little are actually part of this repair process. On chromosomes, DNA forms genes that create proteins. Between these genes, there are DNA sequences.

"People have thought that this DNA didn't do anything," note Dr. Adar. "But it turns out that proteins bind to these other DNA sequences, and this affects other nearby or far-away genes. Our analysis shows that these DNA regulatory sequences are also being repaired. So, if they're being repaired, then they're likely important. And now we can find their locations throughout the genome."

Friday, May 01, 2015

Source: iStock/icefront

Placebo responders are different from placebo nonresponders, with implications for the design of clinical trials and the provision of clinical care. Placebo responders, for example, are thought to have brain signaling pathways that differ in subtle ways from nonresponders’ pathways. Ultimately, these pathways—especially the dopamine, opioid, endocannabinoid, and serotonin pathways—differ at the genetic level.

The genes or gene patterns that affect the placebo response are bound to be extensive—so extensive, in fact, that they may merit the term placebome. The term already graces the title of a paper prepared by researchers at the Beth Israel Deaconess Medical Center. This paper—“Genetics and the placebo effect: the placebome”—appeared April 13 in the journal Trends in Molecular Medicine.

“Evidence that genetic variations in these pathways can modify placebo effects raises the possibility of using genetic screening to identify placebo responders and thereby increase randomized clinical trial efficacy and improve therapeutic care,” the researchers proposed. “Furthermore, the possibility of interaction between placebo and drug molecular pathways warrants consideration in randomized clinical trial design.”

For the rest of the story, click here.

Friday, May 01, 2015

Source: iStock/Aldo Murillo

Cell-free DNA from the maternal blood of a pregnant woman can throw clinicians a curve. Such DNA can indicate whether the genome of a developing fetus contains an abnormal number of chromosomes. Or it may simply indicate that the pregnant woman’s genome contains copy number variants (CNVs). If the latter possibility is not taken into account, a prenatal screen could yield a false-positive result. For example, the screen could overstate the odds that a developing fetus is at risk of certain genetic conditions, such as a chromosome trisomy.

The newer prenatal screens that rely on cell-free DNA have shown high sensitivity and specificity. Yet these tests have limited positive predictive value because the overall incidence of aneuploidy is low. As these prenatal screens become more common, false-positive results may become more worrisome.

This possibility was explored by researchers at the University of Washington, Fred Hutchinson Cancer Research Institute, and the Howard Hughes Medical Institute. These researchers investigated four pregnancies with discordant prenatal test results.

For the rest of the story, click here.

Friday, May 01, 2015

Polygenic risk scoring can help to identify women in higher risk categories who may benefit from interventions such as MRIs, chemoprevention, or even prophylactic mastectomies. [iStock/Wavebreak]

Many gene variants, one genetic profile—that’s the approach Mayo Clinic scientists are using to personalize breast cancer prediction. The relevant gene variants here are common variants that contribute little to a person’s overall risk of developing breast cancer—at least when they are considered individually. In combination, however, these variants constitute a powerful risk factor, one that offers clinicians as much guidance as breast density or family history.

What’s more, the combination approach does not merely duplicate the predictions based on existing breast cancer risk models. It provides an independent risk factor. Accordingly, it could be integrated with existing models, improving their predictive powers.

For the rest of the story, click here.

Friday, May 01, 2015

Source: iStock/Evgeny Terentev

Many of the mutations that are found with tumor-only genetic sequencing are not actually tumor-related. Instead, they are just germline mutations, which are inherited changes that differ from person to person. They are common in normal tissues, and they are not necessarily related to cancer.

Tumor-only genetic sequencing, then, may lead personalized cancer therapies astray—unless genomic information from a patient’s tumor is compared with genomic information from the patient’s normal tissue. Without this check, innocuous genetic changes may be thought “actionable” and therapies thought “targeted” may stray wide of the mark.

Essentially, the problem is a failure to distinguish between positive results and false-positive results. The scale of the problem, warn scientists from Johns Hopkins University and Personal Genome Diagnostics, is considerable.

For the rest of the story, click here.

Nina Peled, Ph.D., and Plamena Entcheva-Dimitrov, Ph.D.

Friday, May 01, 2015

Advocacy groups have alleged that the FDA lacks statutory authority to regulate LDTs, that the agency would not be able to bear the burden, and that the use of a guidance document circumvents requirements of rulemaking. [iStock/shock]

The FDA defines a laboratory developed test (LDT) as a type of in vitro diagnostic device (IVD) intended for clinical use that is designed, manufactured, and used within a single laboratory. According to the FDA, enforcement discretion with respect to LDTs had been exercised because they were traditionally simple, small-scale testing laboratories, serving a limited local population and were typically used and interpreted directly by physicians working within a single institution.

As technology has advanced, LDT labs have been able not only to further the uniqueness, sophistication, and complexity of their tests, but also to offer them across state boundaries. While such advances strive to improve health outcomes, the FDA feels that they no longer fit the above narrow definition of a “Traditional LDT.” From a perspective of risk to public health, the distinction between a test manufactured in a lab and one produced by a conventional IVD manufacturer has become blurred, yet only the latter is subject to the FDA’s scrutiny and oversight.  

For the rest of the story, click here.

Gail Dutton

Friday, May 01, 2015

AAA currently has 17 production and research and development facilities that manufacture both diagnostic and therapeutic molecular nuclear medicine products.

Advanced Accelerator Applications (AAA) is pioneering work in theragnostics—the blending of therapeutics and diagnostics capabilities into one drug for nuclear medicine applications.

“Theragnostics is a very straightforward proposition for physicians dealing with nuclear medicine,” says Stefano Buono, AAA’s CEO and founder. This approach attaches radioisotopes to therapeutic molecules to deliver therapeutics and imaging in one injection. “The isotopes don’t change the nature of the chemical entity, and they don’t change the ability for targeting,” he explains.

Traditionally, most radioactive compounds used in healthcare are active about 10 hours. AAA has produced more than 30,000 batches of such compounds for medical centers since spinning out of CERN in 2002. The company has expanded its work to include therapeutic compounds. “We can make therapeutic, radioactive compounds that have a three-day window,” Buono asserts.

Unlike traditional nuclear medicine approaches, which can’t treat metastatic disease, theragnostics is effective for tumors that are so widespread they can’t be treated with radiotherapy or surgery.

These new capabilities, Buono insists, have the potential to transform nuclear medicine from a niche therapy to “a pillar of medicine.”

For the rest of the story, click here.

Jeffrey S. Buguliskis, Ph.D.

Friday, May 01, 2015

Researchers are being overwhelmed by sequencing data that is accumulating far faster than it be can analyzed. The resulting information log jam has the scientists scrambling for solutions. [iStock/isak55]

Genomics has an obsession, and it’s called Big Data. However, unlike other obsessions, this one will probably not ruin anyone’s life—maybe only a few late nights or weekend plans for the researcher on a tight deadline.

This preoccupation was born out of necessity. It began as an innate need to understand how our genetic makeup controls every facet of human life, from our greatest mental and physical achievements to the debilitating illnesses that render us helpless to our own body systems.

The demand for ever more information by the genomics field began about two decades ago with the advent of microarray technology. This was the first time scientists were introduced to truly large sets of genomic data that required quantitative analysis and training. Assigning values to tiny fluorescent grids on glass slides and then sifting through piles of information about which genes were upregulated or downregulated became a fixation for many research groups. At the time scientific presentations were riddled with heat map displays and descriptions of dye vs probe ratios, clustering, and normalization values. Yet, this was to be just the beginning of the field of genomics’ fascination with mass quantities of data.

For the rest of the story, click here.

Patricia Fitzpatrick Dimond, Ph.D.

Friday, May 01, 2015

Personalized mouse avatars have yet to demonstrate clear changes in the course of a person’s disease, despite the occasional successful anecdote. [iStock/Filo]

Cancer researchers and drug developers continue to say that although gene expression profiling has led to significant advances in cancer diagnosis and prognosis, in vivo animal models that allow translation of therapeutic strategies to the clinic are sorely needed.

Used in research since the 1980s, xenograft models (PDX models) or avatars in which patient tumor samples are grown in immunocompromised mice have proven useful for drug screening and biomarker development. But investigators say that significant hurdles to adoption of the technology as a translational platform remain, including lack of tumor heterogeneity and genetic diversity, both hallmarks of human cancers. The models, they add, fail to replicate the natural tumor microenvironment critical to replicating tissue or organ-specific properties that contribute to tumor progression and modulate therapeutic response. Xenografts also may exclude the important interactions between immune and cancer cells during tumor initiation, maintenance, and metastasis.

Other liabilities to avatar models that may limit their practical use in a research setting include low tumor take rates, slow tumor growth rate, and the need for multiple passages in mice leading to transformation of the original tumors’ character, thereby reducing reliability and making it difficult to get enough mice with tumors to produce statistically reliable results. Production of a tumor model may typically require three to six months, and in the meantime, scientists and suppliers readily say, patients may die of their disease.

For the rest of the story, click here.

Friday, May 01, 2015

The May issue of Clinical OMICs is available now! Check it out by clicking on the link below.

Clinical OMICs Volume 2, Issue No. 5

Friday, May 01, 2015

Telomeric DNA is subject to attrition due to aging, and it accelerates early in cancer. Such attrition, however, slows three to four years before cancer is typically diagnosed. [molekuul.be/Fotolia]

Telomere length hasn’t been a reliable yardstick for measuring the progress of cancer. Because cancer cells divide frequently, and because telomeres shorten with repeated cell division, you might expect cancer cells to age rapidly, and then expire. Yet cancer cells often compensate by making more telomerase enzyme, which prevents the telomeres from getting even shorter. All the same, many cancer cells have very short telomeres. In fact, telomeres in persons developing cancer can look as much as 15 years chronologically older than those of people who are not developing the disease.

To resolve these seemingly contradictory observations, researchers from Northwestern University and Harvard University tracked telomere changes over a fairly long period of time, checking telomere lengths in blood cells at multiple time points. Doing so allowed these researchers to detect a pattern that previous investigators had overlooked. Telomere length shortens dramatically at first, and then stabilizes. And this switch, from fast to slow, occurs three to four year before cancer is typically diagnosed.

The timing of the fast/slow changeover may be telling. That is, it may indicate when cancer hijacks the cell's aging process.

Understanding the pattern of telomere shortening could ultimately yield a new biomarker to predict cancer development with a blood test. This point was emphasized by one of the researchers, Lifang Hou, M.D., Ph.D., a professor of preventive medicine at Northwestern University Feinberg School of Medicine: “Because we saw a strong relationship in the pattern across a wide variety of cancers, with the right testing these procedures could be used to eventually diagnose a wide variety of cancers.”

Dr. Hou is the lead author of an article ("Blood Telomere Length Attrition and Cancer Development in the Normative Aging Study Cohort") that resulted from the Northwestern/Harvard study. This article, which appeared online April 30 in EBioMedicine, describes how scientists took multiple measurements of telomeres over a 13-year period in 792 persons, 135 of whom were eventually diagnosed with different types of cancer, including prostate, skin, lung, leukemia, and others.

"[Relative] to approaching cancer diagnosis, age-adjusted BTL [blood telomere length] attrition decelerated in cancer cases, ultimately yielding significantly elongated BTL and suggesting that critical BTL shortening may contribute to cancer initiation which then, in turn, activates telomere maintenance mechanisms to compensate and further promote cancer," wrote the authors of the article. "Thus, our results may help explain the inconsistent results of previous studies and provide more insight into using BTL as an early detection biomarker of cancer."

The Northwestern/Harvard study is believed to be the first to look at telomere length at more than one time point before diagnosis. That's significant because cancer treatment can shorten telomeres. Post treatment, it's uncertain whether their length has been affected by the cancer or the treatment.

"This likely explains why the previous studies have been so inconsistent," Dr. Hou noted. "We saw the inflection point at which rapid telomere shortening stabilizes. We found cancer has hijacked the telomere shortening in order to flourish in the body."

If scientists can identify how cancer hijacks the cell, Dr. Hou added, perhaps treatments could be developed to cause cancer cells to self-destruct without harming healthy cells.

Wednesday, April 22, 2015

Source: © Monkey Business/Fotolia.com

Promising to bring the benefits of genetic testing to every woman and man, Color Genomics said yesterday it was launching with $15 million in financing, and an immediately-available $249 test for genes linked to breast and ovarian cancers.

The company’s Color Test is designed to analyze mutations in the 19 genes known to be responsible for an inherited predisposition to breast and ovarian cancer—including BRCA1 and BRCA 2. A mutation in the former gene caused actress Angelina Jolie to have a preventive double mastectomy, she disclosed in 2013.

Color says all of its tests are physician-ordered, whether a test-taker’s own physician or one designated by the company. Tests are carried out in the company’s CLIA-certified laboratory, and include access to genetic counseling at no additional cost.

“Color is democratizing access to genetic testing,” the company declared in a blog post announcing its formation. “Every woman should have the choice and opportunity to get tested for her genetic risk of breast and ovarian cancer in an affordable, accessible, high-quality way.”

To that end, Color said, it is partnering with major cancer centers—citing by name University of California, San Francisco (UCSF), and University of Washington Medical Center, and the Abrahamson Cancer Center of the University of Pennsylvania—to provide free testing to women who are unable to afford it, in what the company calls its Every Woman Program. And as part of its purchasing process, Color added, women buying their own tests can opt to donate money to help support a woman who cannot afford testing.

According to the company, men can also benefit from the tests, since they may carry a mutation in one of the 19 genes analyzed that may raise their risk of certain cancers, including male breast cancer.

Headquartered in Burlingame, CA, Color won $15 million in series A financing from VC firms Khosla Ventures and Formation 8, along with funders that include The Home Depot co-founder Ken Langone; Laurene Powell Jobs, Widow of Apple co-founder Steve Jobs; Yahoo co-founder Jerry Yang; and Dropbox co-founder CEO Drew Houston.

“Building a high-quality, but affordable test required significant investments in software design, big data, bio-informatics, CLIA compliance, laboratory automation, and genetics,” Othman  Laraki, Color’s president, said in a statement. “By marrying multiple emerging disciplines, we have developed something many did not think was possible.”

In addition to Laraki, Color’s co-founders include CEO Elad Gil, Ph.D., a former MIT cancer researcher who later served as a product and strategy executive at Twitter and Google; Taylor Sittler, M.D., a former pathologist at UCSF; and founding engineer Nish Bhat, a former security engineer at Lookout and software engineering intern at LinkedIn.

Color’s advisors and scientific collaborators include Mary-Claire King, Ph.D., of the University of Washington, the researcher credited with discovering and naming BRCA1; Tom Walsh, Ph.D., also of UW, and co-developer with Dr. King of the BROCA targeted capture and genomic sequencing approach; and Stan Lapidus, CEO and founder of SynapDx, a developer of lab tests for laboratory tests for autism and other developmental disorders in children, and an MIT instructor who holds over  30 U.S. patents.

Monday, April 20, 2015

Foundation Medicine announces its collaboration with the National Cancer Institute study to further understand the molecular underpinnings that may lead to exceptional responses for drug therapies in patients with cancer. [jessicaphoto/iStock]

The Massachusetts based Foundation Medicine, which develops, manufactures, and sells genomic analysis diagnostics for solid and circulating cancers has announced a collaboration with the National Cancer Institute (NCI) on the Exceptional Responders Initiative (ERI). The alliance is for an exploratory study to investigate the unique molecular indicators of tumors associated with cancer patients with excellent prognosis to drug therapies.

The study will be led by NCI scientists and will include participation from Baylor College of Medicine, Nationwide Children's Hospital, as well as Foundation Medicine tumor samples collected from individuals prior to initiation of the therapy of interest. Samples will be analyzed to determine whether specific molecular determinants can be identified that could be exploited therapeutically. Data from the ERI could radically improve our knowledge of the fundamental differences in survival rates among cancer patients. Moreover, the findings could lead to better clinical diagnostics by identifying previously unknown tumor biomarkers.

“At Foundation Medicine, we are focused on understanding the unique molecular changes that contribute to a patient’s individual disease to inform treatment decisions,” said Vincent Miller, M.D., chief medical officer at Foundation Medicine. “The ERI represents a significant opportunity to utilize advances in precision medicine to better understand outcomes, which can be applied to the future selection of treatments for patients with cancer.”

Exceptional responders represent a small percentage of patients who have experienced an outstanding, but unexpected response to a systemic anticancer treatment. Specifically, these patients represent fewer than 10 percent of patients who have had a complete response or a durable partial response (lasting at least 6 months) based on previous data for the specific tumor type.

“Every oncologist can point to a small number of their patients who have had unusually favorable responses to systemic therapies,” explained Dr. Miller. “By beginning to leverage this experience, largely rooted in community practice, we hope to learn more quickly and generate critical hypotheses which can then be validated in larger cohorts. We are thrilled to participate with Baylor College of Medicine and Nationwide Children’s Hospital in this important NCI-led initiative, which we believe represents the future of oncology care.”

Tissue and clinical data from exceptional responders will be collected at several sources, including NCI-supported clinical trials, clinical studies that are actively enrolling at other institutions, and cases submitted by private practice or community center physicians.

Once the tissue has been obtained and processed at the Biospecimen Core Resource at Nationwide Children's Hospital, the analysis phase will commence using Foundation Medicine's FoundationOne® comprehensive genomic profile test for patients with solid tumors, as well as by whole exome and transcriptome RNA sequencing through the Baylor College of Medicine. The resulting molecular characterization and concordance data will be utilized to determine if opportunities for broader clinical testing exists, in order to accelerate the development of targeted chemotherapies.

Friday, April 17, 2015

Source: © Tyler Olson/shutterstock

Scientists at the Ohio State University Comprehensive Cancer Center have developed a new method for measuring genetic variability within a tumor that might one day help doctors identify patients with aggressive cancers that are more likely to resist therapy.

Researchers used a new scoring technique they developed called MATH (mutant-allele tumor heterogeneity) to measure the genetic variability among cancer cells within tumors from 305 patients with head and neck cancer. High MATH scores corresponded to tumors with many differences among the gene mutations present in different cancer cells.

Cancers that showed high genetic variability, i.e., "intra-tumor heterogeneity," correlated with lower patient survival. If prospective studies verify the findings, MATH scores could help identify the most effective treatment for patients and predict a patient's prognosis.

It’s long been hypothesized that multiple sub-populations of mutated cells within a single cancer lead to worse clinical outcomes; however, oncologists do not use tumor heterogeneity to guide clinical care decisions or assess disease prognosis because there is no single, easy-to-implement method of doing so in clinical practice.

To address this need, James Rocco, M.D., Ph.D., and his colleagues developed MATH to make it easier for doctors to measure genetic variability in patients' tumors and to help guide treatment decisions. Their study (“Intra-tumor Genetic Heterogeneity and Mortality in Head and Neck Cancer: Analysis of Data from The Cancer Genome Atlas”), reported in PLOS Medicine, confirms that high genetic variability with a patient's tumor is related to increased mortality in head and neck squamous cell carcinoma.

"Genetic variability within tumors is likely why people fail treatment," says Dr. Rocco, professor and John and Mary Alford Chair of Head and Neck Surgery. "In patients who have high heterogeneity tumors it is likely that there are several clusters of underlying mutations, in the same tumor, driving the cancer. So their tumors are likely to have some cells that are already resistant to any particular therapy."

For the current study, Dr. Rocco and his team used the MATH tool to analyze retrospective data from 305 head and neck squamous cell carcinoma patients from The Cancer Genome Atlas (TCGA). This NIH repository of publicly available data was launched in 2006 as a pilot project and now includes samples from more than 11,000 patients across 33 tumor types. The MATH score was calculated from data obtained by TCGA via whole-exome sequencing.

Researchers confirmed that high intra-tumor heterogeneity was related to increased mortality in this sub segment of patients. Each 10% increase in MATH score corresponded to an 8.8% increased likelihood of death.

“To our knowledge this study is the first to combine data from hundreds of patients, treated at multiple institutions, to document a relation between intra-tumor heterogeneity and overall survival in any type of cancer,” wrote the investigators. “We suggest applying the simply calculated MATH metric of heterogeneity to prospective studies of HNSCC and other tumor types.”

Tuesday, April 14, 2015

Source: © AlexRaths/iStock

Roche’s Ventana Medical Systems said today it has inked a master collaboration agreement with Astellas Pharma to develop new automated tissue diagnostics to support therapeutic compounds in development. The value of the collaboration was not disclosed.

Initial projects related to the collaboration will center on creating a diagnostic test intended to support early-stage clinical trials for Astellas’ Phase I cancer compound ASP5878.

ASP5878 is a small-molecule fibroblast growth factor receptor (FGFR) inhibitor designed to fight cancer by blocking the kinase activities of FGFR1, FGFR2, FGFR3 and FGFR4. ASP5878 was developed in-house.

Ventana said it will develop, in parallel with ASP5878, an immunohistochemistry (IHC) test identifying FGF19 in certain solid tumors.

IHC is one of Ventana’s seven product areas; the other six include in situ hybridization (ISH), hematoxylin and eosin (H&E), special stains, companion diagnostics, advanced workflow, and image analysis.

“We are pleased to expand our relationship with Astellas with this master companion diagnostic agreement, which allows our collaborative projects to quickly move from early stage biomarker hypothesis testing to late stage companion diagnostic development with Astellas' targeted therapies in oncology,” Doug Ward, vp, Ventana Companion Diagnostics, said in a statement.

Monday, April 13, 2015

Source: © Jaimie Duplass/Fotolia.com

Roche acquired CAPP Medical, a genomics research company founded by Stanford University oncologists and industry veterans, to advance technology development for cancer screening and monitoring through the detection of circulating tumor DNA (ctDNA) in blood. CAPP Medical's technology is designed to isolate and quantify small amounts of ctDNA through a simple blood draw, which has the potential to be used for cancer therapy selection and monitoring tumor response and resistance to therapy, according to Roche officials.

"Roche believes focused and high quality next generation sequencing assays using simple blood draws have the potential to significantly advance the time of cancer diagnosis and change routine cancer diagnostic monitoring and may be highly cost effective compared to today's current standard of using PET and CT imaging to monitor tumor progression," said Roland Diggelmann, COO Roche Diagnostics. "CAPP Medical's technology for detecting the circulating cancer DNA from blood has the potential to further strengthen Roche's diagnostic offerings for patients and will provide valuable clinical trial support for Pharma oncology pipelines."

Alex Philippidis

Friday, April 10, 2015

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Rosetta Genomics said today it has agreed to acquire CynoGen, which does business as PersonalizeDx, from Prelude, in a purchase that expands the buyer’s presence and product offerings in oncology diagnostics.

The acquisition will also create a combined pipeline for Rosetta Genomics that is set to introduce to market five new assays within the next 12 months. One of them is a thyroid neoplasia assay scheduled for launch in the third quarter of 2015.

Those tests will join Rosetta Genomics offerings that now include the Rosetta Cancer Origin Test™, the Rosetta Lung Cancer Test™, and the Rosetta Kidney Cancer Test™—as well as the Rosetta Genomics PGxOne™ test, and EGFR and KRAS sequencing services for Admera Health.

PresonalizeDx provides molecular diagnostics and services that include tests in prostate, bladder, and lung cancer.

Rosetta Genomics said the deal will create “multiple areas of product synergies” with PersonalizeDx, notably in urologic and lung cancers. The combined company plans to add PersonalizeDx Fluorescence in situ Hybridization (FISH) and molecular markers for actionable genomic targets to a recently created combination of Rosetta’s Lung Cancer Test and Admera Health’s genomic markers for targeted therapies.

In addition to the tests, Rosetta Genomics said, the acquisition will give the company commercial and laboratory operations capabilities, and a high-complexity CLIA laboratory in Lake Forest, CA.

“The PersonalizeDx business is an excellent strategic and cultural fit, and we look forward to combining their assays and biomarkers with our current and future microRNA-based and other assays,” Kenneth A. Berlin, Rosetta Genomics’ president and CEO, said in a statement.

The combined company is projected to generate revenues this year ranging from $10 million and $12 million, rising to $18 million in 2016. The following year, Rosetta Genetics expects to rack up positive earnings before interest, taxes, depreciation and amortization (EBITDA), and positive cash flow from operations.

Rosetta Genomics agreed to pay $2 million in cash, 500,000 ordinary shares of company stock—valued at the close of trading today at $1.65 million, based on a $3.30 per share closing price, up 12% from yesterday. Rosetta also agreed to shell out undisclosed “specified assets” and certain services to be provided to Prelude. In return, Rosetta Genomics said, it will gain marketing rights to Prelude’s assay for ductal carcinoma in situ (DCIS).

The deal is set to close “in the next several weeks,” Rosetta Genomics said, and is tied to Prelude purchasing PersonalizedDx from another entity. Prelude is one of 10 companies in the portfolio of tech accelerator Fjord Ventures.

Thursday, April 02, 2015

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Researchers report that the Harmony prenatal test by Ariosa Diagnostics undertaken between 10 to 14 weeks of pregnancy may be more effective in diagnosing Down syndrome and two other less common chromosomal abnormalities than standard noninvasive screening techniques.

In the study (“Cell-free DNA Analysis for Noninvasive Examination of Trisomy”) published in the New England Journal of Medicine, which followed pregnancy outcomes in close to 16,000 women, the cell-free DNA blood test resulted in correctly identifying all 38 fetuses with Down syndrome. The diagnosis was confirmed by newborn exam, prenatal, or postnatal genetic analysis.

“In this large, routine prenatal-screening population, cfDNA testing for trisomy 21 had higher sensitivity, a lower false positive rate, and higher positive predictive value than did standard screening with the measurement of nuchal translucency and biochemical analytes,” wrote the investigators.

The test focuses on the small percentage of fetal DNA found floating in a pregnant woman’s blood. DNA is amplified via PCR and sequenced so that comparisons can be made between relative amounts of each chromosome’s DNA. A greater quantity of DNA is indicative of some chromosomal conditions, including Down syndrome, which is characterized by an extra copy of chromosome 21.

When the same women underwent standard screening, 30 of the 38 fetuses with Down syndrome were flagged. The screening comprises a blood draw in which hormones and proteins associated with chromosomal defects are identified, together with an ultrasound of the nuchal fold fluid in the back of the neck, an excess of which is suggestive of Down syndrome.

The average age of the pregnant women was 30 and approximately one-quarter were over 35, the age at which women have traditionally been considered high risk and offered prenatal invasive testing with procedures like amniocentesis.

A second advantage of cell-free DNA analysis reported by the researchers, who were led by first author Mary Norton, M.D., professor of clinical obstetrics and gynecology at the University of California-San Francisco, was the relatively low incidence of Down syndrome misdiagnoses. While standard testing is acknowledged to result in a large number of false positives, these were significantly less likely with the cell-free DNA tool. There were nine false positives resulting from this method, vs. 854 with standard  screening.

While far fewer cases of two other less common chromosomal abnormalities were found in the study population, the accuracy of cell-free DNA screening still surpassed the standard screening method, according to Dr. Norton. Among 10 cases of trisomy 18, also known as Edwards syndrome, the cell-free DNA technique pinpointed nine and flagged one false positive. With standard screening, eight were identified and there were 49 false positives.

For trisomy 13, also known as Patau syndrome, the cell-free DNA test identified both cases and flagged one false positive, while standard screening identified one case and flagged 28 false positives.

Dr. Norton said that since use of the cell-free DNA test will result in far fewer false positives than current screening, it can consequently reduce the number of invasive tests and miscarriages attributed to them. However, patients should be made aware of its limitations, she added.

“Providers need to be attuned to patients’ preferences and counsel them about the differences in prenatal screening and diagnostic testing options. Those women who do opt for cell-free DNA testing should be informed that it is highly accurate for Down syndrome, but it focuses on a small number of chromosomal abnormalities and does not provide the comprehensive assessment available with other approaches.

“Counseling should also include information about the risks associated with failed tests and the pros and cons of pursuing invasive testing if no results are obtained,” she said.

Gail Dutton

Wednesday, April 01, 2015

Cynvenio Biosystems developed LiquidBiopsy, a platform that utilizes a blood sample to perform sequence analysis and genomic reporting. This platform gives doctors and cancer researchers the ability to perform next-generation sequencing on rare populations of circulating tumor cells and cell-free DNA from whole blood.

Cynvenio Biosystems, with its LiquidBiopsy® rare cell isolation and genomic analysis platform, is at the forefront of cancer diagnostics. Rather than rely on tissue biopsies or counting circulating tumor cells in the blood, this technology extracts and sequences those cells’ DNA. That, in turn, makes possible real-time analysis of specific alterations within tumors that affect treatment decisions.

Historically, blood draws have merely counted circulating tumor cells. “That doesn’t provide a decision point,” says Paul Dempsey, Cynvenio’s CSO. The molecular analysis of circulating tumor cells, however, enables physicians to design treatment regimens based upon their molecular character and, thus, improve outcomes.

Not only are blood samples easier to obtain, but “blood draws let physicians sample tumor cells at intervals through patients’ treatment, remission, and potential recurrence,” Dr. Dempsey explains. “Cancer is a dynamic, quickly moving disease that needs to be monitored over time.

For the rest of the story, click here.

Lisa Heiden, Ph.D.

Wednesday, April 01, 2015

Trovagene’s Next Generation SamplingSM technology can be used to interrogate an ultra-short DNA sequence (~30 bp), yielding data that can show how mutations react to therapy over time. As tumor cells die through treatment or natural processes, small fragments of DNA are released into the blood and the urine. Measuring this circulating tumor DNA offers a new way to track cancer-related gene mutations at the molecular level.

Oncology has risen to the forefront of genomic profiling, which is being used to identify actionable driver mutations and other markers. These markers can help clinicians design therapies and monitor patient responses, and they may be revealed by means of next-generation sequencing (NGS), a catch-all term describing massive parallel sequencing technologies generating gigabases of data.

NGS is already established as a research platform, and it is rapidly gaining acceptance as a clinical platform—at least as far as technical and scientific matters are concerned. Administratively and practically, however, NGS still faces barriers to adoption as a clinical tool. These include regulation, incorporation in clinical guidelines (NCCN, ASCO, etc.), reimbursement, and physician and patient education.

Accordingly, if NGS is to be fully embraced by the clinic, and if the potential for personalized oncology is to be realized, interested parties will have to cooperate and build a sense of shared commitment—at least, that was the sentiment expressed by several of the presenters at the Personalized Medicine World Conference, which was held recently in Mountain View, CA.

For the rest of the story, click here.

Jeffrey S. Buguliskis, Ph.D.

Wednesday, April 01, 2015

It will be absolutely essential for doctors to explain to their patients why some types of genomic information might be clinically actionable while other kinds are inconsequential. [© Science Photo/Fotolia]

It seems every week that a new publication extols the benefits of next-generation sequencing (NGS), often from sequencing the genome of a medically relevant organism in record time or identifying the polymorphisms that may lead to drug resistance in cancer. One could make an educated guess that NGS is poised to tackle almost any clinical issue facing precision medicine. But what about the glut of genomic data that is unavoidably generated from patient samples with each sequencing event? Is there relevant data from those samples that is clinically actionable, disparate from the initial clinical presentation? These are some of the current questions that physicians and clinical researchers will have to face as they foray into the personal genomics era.

With the ever increasing availability of direct-to-consumer genetic testing, coupled with the accelerated fall in costs for whole-genome and exome sequencing (WGS and WES), the opportunity for individuals to analyze their own genomic data and take greater control of their healthcare decisions will be abundant. Patients will want to know what genomic biomarkers are and how they are relevant to everyday health or their current medical condition.

For the rest of the story, click here.

Jeffrey S. Buguliskis, Ph.D.

Wednesday, April 01, 2015

With next-generation sequencing, it is possible to distinguish between inherited and de novo mutations. What's more, it is possible to distinguish between de novo mutations that drive cancer and those that are "along for the ride." [© royaltystockphoto/iStock]

Conventional wisdom has steered scientists for many years toward the assumption that disease-triggering genetic mutations were inherited by offspring from existing mutations within parental DNA, and that these mutations reside within all somatic cells, eventually emerging due to some perturbation of the cellular environment. However, over the past several years experimental and genomic data has shown that many of the mutations that lead to carcinogenesis originate somatically, i.e., de novo  mutations generated in offspring that are undetectable in either parent.

While inherited (germline) mutations are ascribable, since they follow familial genetic patterns, the underlying causes and traceability of somatic mutations has been problematic for many years. However, due to the increased accessibility and cost effectiveness of next-generation sequencing (NGS) techniques such as whole- genome sequencing (WGS) and whole-exome sequencing (WES), researchers have been able to readily identify somatic mutations and begin to categorize them based on the nature of the mutation, as well as the tissue from where it was derived.

For the rest of the story, click here.

Wednesday, April 01, 2015

The April issue of Clinical OMICs is available now! Check it out by clicking on the link below.

Clinical OMICs Volume 2, Issue No. 4

Monday, March 30, 2015

A new MRI technique shows that mucin-attached sugars generate a high MRI signal (left) compared to cancerous cells (right) [Xiaolei Song/Johns Hopkins Medicine]

The holy grail of clinical diagnostics would be a completely noninvasive technique that can identify disease with exceptional accuracy. Unfortunately, science has yet to achieve this almost essential goal. However, new research from Johns Hopkins scientists may provide the crucial data required to take a big leap toward complete noninvasive diagnoses.

Imaging tests such as mammograms or CT scans can often detect tumor growth within tissues, but determining if that growth is cancerous almost always requires a biopsy in order to study cells from the mass directly.

Conversely, the results from the current study would suggest that MRI’s could make many biopsies obsolete by tuning the machines to detect the glycosylation pattern of a specific glycoprotein that is often shed by the outer membranes of cancerous cells.      

"We think this is the first time scientists have found a use in imaging cellular slime," said Jeff Bulte, Ph.D., professor of radiology and radiological science in the Institute for Cell Engineering at the Johns Hopkins University School of Medicine and senior author on the study. "As cells become cancerous, some proteins on their outer membranes shed sugar molecules and become less slimy, perhaps because they're crowded closer together. If we tune the MRI to detect sugars attached to a particular protein, we can see the difference between normal and cancerous cells."

The findings from this study were published recently in Nature Communications through an article entitled "Label-free in vivo molecular imaging of underglycosylated mucin-1 expression in tumour cells."

Previous studies have found that the glycoprotein mucin-1 is overexpressed and underglycosylated in most malignant adenocarcinomas of epithelial origin, for example, colon, ovarian, and breast cancer. Moreover, aberrant expression of mucin-1 has been seen in almost 65% of the 1.4 million tumors diagnosed each year in the United States.

Dr. Bulte and his team wanted to take advantage of these telltale signs for tumor growth by fine-tuning an MRI technique that detects a unique interaction of glucose with its surrounding water molecules without administering dyes. The researchers were able to compare mucins, with and without their sugar moieties, to observe how the MRI signal changed. The team then used the same technique to analyze four types of in vitro cancer cells, in which they were able to detect markedly lower levels of mucin glycosylation in comparison to normal cells.       

"The advantage of detecting a molecule already inside the body is that we can potentially image the entire tumor," explained Xiaolei Song, Ph.D., research associate in Dr. Bulte's laboratory and lead author on the study. "This often isn't possible with injected dyes because they only reach part of the tumor. Plus, the dyes are expensive."

The next step for the Johns Hopkins group is to see if they can distinguish a variety of cancerous tumors in living mice. Though Dr. Bulte and his team are optimistic about their current findings they did caution that there is much more testing that needs to be done to prove that the technique has value for clinical diagnostics in human cancers.

Thursday, March 26, 2015

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Ten biopharma companies have joined together to create the Genomics Expert Network for Enterprises (GENE) Consortium, which will oversee a year-long trial designed to integrate industry expertise into the 100,000 Genomes Project—the U.K.’s effort to catapult itself to global leadership in genetic research into cancer and rare diseases.

Through the GENE Consortium, the companies will work to discover how best to collaborate with clinicians and researchers in studying a selection of whole genome sequences across cancer and rare diseases. The consortium’s work is intended to accelerate the development of new diagnostics and treatments for patients, said Genomics England, the entity created by the U.K. Department of Health to run the 100,000 Genomes Project.

The GENE Consortium’s 10 companies are: AbbVie, Alexion Pharmaceuticals, AstraZeneca, Biogen (which changed its name from Biogen Idec as of Monday), Dimension Therapeutics, GlaxoSmithKline, Helomics, Roche, Takeda, and UCB—whose participation is subject to contract negotiation and signature, Genomics England added.

“We are particularly looking forward to contributing our expertise in understanding the role of biomarkers and personalised healthcare in the development of targeted medicines for patients,” Mene Pangalos, Ph.D., AstraZeneca’s evp of innovative medicines and early development, said in a statement.

Helomics said in a company statement it will provide its PCAPTM tumor profiling technology and diagnostics-focused expertise to the consortium. The company said its goal was to identify new biomarkers that could be used to develop more advanced cancer diagnostic tests and ultimately lead to new levels of personalized medicine.

Genomics England also disclosed the areas where leading clinicians and scientists across the U.K. will explore within Genomics England’s Clinical Interpretation Partnership (GeCIP), formed to identify scientific findings and medical discoveries from the 100,000 Genomes dataset.

As part of GeCIP, more than 28 teams or “domains” will be established for clinical and research experts in which to work. These include rare disease—a category it said will include cardiovascular, neurological, paediatrics domains—as well as cancers; pan-cancer analysis across many cancers; functional effects on gene expression, proteins and life-long DNA changes; electronic health records research; ethics, law and social science; health economics; validation and feedback.

The 28 were selected from 88 applications to join GeCIP made by more than 2,000 researchers, clinicians, analysts, and trainees following a call to the research community in November 2014, Genomics England said.

GeCIP—whose members will include academic institutions, the National Health Service (NHS) Genomic Medicine Centres and industry—will ultimately bring together more than 4,000 U.K. clinicians and scientists, as well as over 500 international collaborators specializing in genomic medicine, Professor Mark Caulfield, M.D., FMedSci, chief scientist for Genomics England, said in a statement.

“We hope that this unique collaboration will lead to earlier and more precise diagnoses for patients and, working with companies, will pave the way for new, more targeted therapies and treatments,” Professor Caulfield added.

According to Genomics England, nearly 3,000 genomes have been sequenced to date as part of the 100,000 Genomes Project, launched in late 2012 by U.K. Prime Minister David Cameron with the goal of mapping 100,000 human genomes from NHS patients by 2017. The project is focusing on patients with rare diseases, and their families, as well as patients with common cancers.

Last year, Illumina, the U.K., and the Wellcome Trust agreed to spend £311 million (nearly $464 million) over four years on the project, which relies on a public-private partnership formed between sequencing giant Illumina and Genomics England.

Tuesday, March 24, 2015

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IntegraGen will oversee high-throughput sequencing activities for the National Reference Center (NRC) and microbiological collections at the Institut Pasteur.

The partnership’s primary objective, according to IntegraGen, is to increase access to next-generation sequencing technologies for the 15 NRCs and the institute’s microbiology collection. The partnership also aims to establish reference tools for the typing of bacterial, viral, and fungal strains.

Additionally, IntegraGen said, it will develop management software tailored to the Institut Pasteur’s internal needs.

“This agreement also represents an opportunity for us to expand our genomics business and to continue to grow our revenue,” IntegraGen CEO Bernard Courtieu said in a statement.

The publicly traded company finished last year with revenue of €6 million (nearly $6.6 million), an increase of 12% over 2013. In addition to identifying biomarkers and commercializing molecular diagnostic tests for autism and oncology, IntegraGen provides genomic services to academic researchers and life sciences companies.

Last month, the company announced the launch of GeCo, a genomic consulting service directed toward academic and corporate genomics researchers.

“Having access to IntegraGen's know-how in high-throughput sequencing is a major asset to reinforce our mobilization abilities and to ensure our mission for public health at the highest level,” added professor Christian Bréchot, M.D., Ph.D., general manager of the Institut Pasteur.

Tuesday, March 24, 2015

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Dako, an Agilent Technologies company specializing in providing cancer diagnostics, said today it has again expanded a three-year-old collaboration with Amgen focused on companion diagnostics.

The value of the expanded collaboration and other financial terms were not disclosed. Dako said the expanded “multi-year” collaboration will allow both companies to benefit from knowledge-sharing within drug-diagnostic R&D, particularly in relation to companion diagnostic products.

“Together we will continue our work in the development of high-quality companion diagnostic products to enable physicians and pathologists to identify cancer patients who are more likely to respond to a specific therapy,” Jacob Thaysen, president of Agilent's Diagnostics and Genomics Group, said in a statement.

Dako and Amgen launched their collaboration in January 2012, when they agreed to develop a diagnostic test for an undisclosed Amgen drug candidate that Dako said was “targeted for a rare and deadly cancer.” A month later, the companies began a second collaboration to develop pharmDx™ for an undisclosed Amgen cancer drug candidate in clinical development. Dako was acquired by Agilent in May 2012 for $2.2 billion.

Amgen’s online pipeline, last updated February 12,  lists six Phase I compounds with cancer indications, as well as three Phase II and five Phase III compounds.

Last year the companies expanded their partnership, as Dako initiated a new project with Amgen to develop a molecular diagnostic test using Dako’s IQFISH hybridization buffer.

The IQFISH hybridization buffer, introduced by Dako in 2012, is designed to slash diagnostic test turnaround time from 17 hours to just 3.5 hours. It enables pathology labs—for the first time—to run DNA-based hybridization assays quickly, with distinct and higher fluorescent signal intensity compared to traditional FISH assays.

Amgen is among several biopharma giants with which Dako has teamed up. Last year, Dako launched a collaboration with Merck & Co. to develop a companion diagnostic test designed to analyze the potential tumor biomarker PD-L1, as part of the clinical development program for Merck & Co.’s investigational anti-PD-1 antibody under study as a potential cancer treatment.

In the two years preceding the Amgen deal, Dako inked agreements with AstraZeneca, Bristol-Myers Squibb, and Roche’s Genentech subsidiary.

Tuesday, March 17, 2015

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Qiagen acquired AdnaGen’s circulating tumor cell (CTC) enrichment technology to boost its capabilities in liquid biopsies. Separately, the company formed a partnership with Tokai Pharmaceuticals to combine its new CTC technology with a molecular assay to co-develop and commercialize a companion diagnostic for Tokai’s galeterone, which is in late-stage clinical trials for treatment of castration-resistant prostate cancer (CRPC). The noninvasive test will determine the expression of the AR-V7 biomarker, which in recent studies has demonstrated potential utility to guide therapy choice in CRPC patients, according to Qiagen officials.

“Following the success of the first-ever regulated companion diagnostic for solid tumors based on molecular biomarkers from a liquid biopsy in Europe, we are expanding our portfolio of highly accurate tests that analyze samples of body fluids that are noninvasive and more accessible than traditional tissue biopsies,” said Peer M. Schatz, CEO of Qiagen. “Our partnership with Tokai Pharmaceuticals, one of the collaborations which we are pursuing with pharma in this area, is expected to result in a liquid biopsy, CTC-based companion diagnostic, with potential to enhance outcomes for prostate cancer patients.”

AdnaGen’s CTC method relies on magnetic particles in an antibody mixture that isolates and purifies mRNA for analysis using RT-PCR. The test for Tokai will be developed by Qiagen Manchester, the global center for the development and regulatory approval of Qiagen’s molecular diagnostic applications.

Friday, March 13, 2015

Richard Scheller, Ph.D., is the new CSO and head of therapeutics at 23andMe.

Less than a month after winning its first FDA authorization, 23andMe is expanding beyond direct-to-consumer genetic testing by creating a new therapeutics group, and appointing Genentech’s recently retired evp of research and early development to lead the new unit.

Richard Scheller, Ph.D., has been named 23andMe’s CSO and head of therapeutics, effective at the beginning of next month. At the new 23andMe Therapeutics, Dr. Scheller will be charged with building a dedicated R&D team that will apply human genetic data toward new therapies for both common and rare diseases.

23andMe said it will link the work of the new therapeutics group with its research platform, which the company says includes the world's largest consented, re-contactable database. That database includes almost 900,000 customers who have contributed more than 250 million data points of information. Over 80% of customers chose to opt-in to research and answer questions, according to 23andMe.

“The same way we are transforming the way people access and understand their genomes, we hope to transform the way we discover and develop novel therapies. By starting with genetic information and understanding the basics of disease, we hope we can make discoveries that will have a meaningful impact on society,” 23andMe CEO and co-founder Anne Wojcicki said today in a post on the company’s blog.

“Our mission is to help people access, understand and benefit from the human genome. With Dr. Scheller joining the team, we believe we will be putting our best efforts into helping customers and society benefit from the human genome,” Wojcicki added. “We believe we have the potential to be the source of new discoveries that transform the health and lives of our friends and family.”

23andMe’s hiring of Dr. Scheller comes some two months after the company launched separate collaborations with a pair of drug developers. On January 12, 23andMe said it gave access to its research platform to Pfizer under a collaboration that will include genome-wide association studies, surveys, and clinical trial recruitment. The partners agreed to undertake a longitudinal study designed to better understand the genetics of lupus by enrolling and genotyping 5,000 people into a new lupus research community. That effort will include integration of medical records, targeted bio-sampling along with genetic information for all participants.

Six days earlier on January 6, 23andMe joined with Genentech in a partnership to generate whole genome sequencing data for about 3,000 people in 23andMe’s Parkinson’s disease community. The company said the multiyear collaboration—whose value has not been disclosed but according to one report was worth $60 million—was intended to identify new therapeutic targets for treating Parkinson’s disease.

Dr. Scheller retired in December 2014 from Genentech, a Roche subsidiary, after 14 years with the company—the last six as evp of research and early development. In that position, he led the company's research strategy, drug discovery, business development, and early drug development activities through proof-of-concept in the clinic. Dr. Scheller also oversaw Genentech’s basic research around oncology, immunology, neuroscience, and infectious disease.

Dr. Scheller served on the faculty of Stanford University for 19 years as a professor in the department of biological sciences and the department of molecular and cellular physiology and was an investigator at the Howard Hughes Medical Institute of Stanford University Medical Center. Since 2004, Dr. Scheller has also served as an adjunct professor in the department of biochemistry and biophysics at the University of California, San Francisco. He has published more than 280 research studies.

For his work elucidating the molecular mechanisms governing neurotransmitter release, Dr. Scheller has received several awards—including the 2014 California Institute of Technology's Caltech Distinguished Alumni Award, and the Albert Lasker Basic Medical Research Award a year earlier. Dr. Scheller was awarded his Ph.D. in chemistry from Caltech, and completed postdoctoral fellowships at the school’s division of biology, as well as at Columbia University’s College of Physicians and Surgeons, where he specialized in molecular neurobiology.

Friday, March 13, 2015

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Tute Genomics said today a company database containing 8.5 billion annotations of genetic variants will be made publicly accessible through Google Genomics, through a partnership with Google as well as Xiaoming Liu, Ph.D., and his team at the University of Texas, Houston Health Science Center’s Human Genetics Center.

According to its main page on Google Genomics, the Tute Genomics Annotation database consists of a curated collection of functional annotations for all possible single nucleotide variants (SNVs) in the human genome (hg19 build).

Data sources include clinical annotations from the National Center for Biotechnology Information’s ClinVar database, and the genome-wide association studies (GWAS) catalog; allele frequencies from the 1000 Genomes Project and National Heart, Lung, and Blood Institute Exome Sequencing Project (NHLBI-ESP) 6500 exomes.

Additional data sources include the Exome Aggregation Consortium 60,000 samples gene and transcript model annotations, such as amino acid and protein substitutions and the functional consequence of exonic variants. Additionally, the database includes conservation and evolutionary scores from tools like SIFT, PolyPhen2, PhyloP, MutationTaster, MutationAssessor, FATHMM, MetaLR, and MetaSVM.

Finally, the database contains Tute-developed scoring system to predict whether a SNP or indel is likely to be associated with Mendelian phenotypes. According to Tute Genomics, the clinical genome interpretation platform is designed to assist researchers in identifying disease genes and biomarkers, as well as assist clinicians/labs in performing genetic diagnosis and personalized therapeutics. Tute draws on expertise that developed the genome annotation and interpretation software ANNOVAR.

“The time is coming when genome sequencing will be part of routine clinical care, and open access to genetic variant databases is a necessary step in order to accelerate progress towards precision medicine,” Tute Genomics CEO Reid Robison, M.D., M.B.A., said in a statement.

Tuesday, March 10, 2015

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Illumina said today it launched a collaboration with Merck Serono—the biopharma unit of Merck KGaA—intended to develop a universal next-generation sequencing (NGS)-based oncology diagnostic. The value of the collaboration was not disclosed.

While saying it would continue pursuing separate collaborations announced in August 2014 with AstraZeneca, Johnson & Johnson’s Janssen Biotech, and Sanofi, Illumina said it will also work with Merck Serono to create a universal test system for clinical trials of targeted cancer therapies, with the goal of creating a more comprehensive tool for precision medicine.

Illumina said it is working with Merck Serono to develop assays that detect and measure multiple variants simultaneously to support clinical trials. The collaboration toward the universal cancer test will include test development, worldwide regulatory approvals, and global commercialization.

“This agreement is another step forward in realizing the promise of precision medicine," Illumina CMO Richard Klausner, M.D., said in a statement. He cited President Obama’s proposed $270 million Personalized Medicine Initiative, which has called in part for expanding genetically-based clinical trials as a key approach for developing better treatments for cancer.

Added Susan Herbert, Head of Global Business Development at Merck Serono: "Our collaboration with Illumina around next-generation sequencing will enable us to perform genome studies at a pace unheard of a few years ago, and could lead to the development of several diagnostics.”

In detailing its efforts toward a Universal Oncology Test System last year, Illumina articulated four objectives:

• Standardize: Enable standardization of a multiplexed platform for evaluating relevant genes.
• Streamline: Optimize the introduction of new biomarkers by using a standardized system.
• Decentralize: Deliver a universal platform for decentralized routine testing, enabling rapid commercial access.
• Collaborate: Facilitate combination trials within and across pharmaceutical companies.

“The benefits of this NGS-based tumor assessment assay will be numerous. For pharmaceutical companies, it will streamline the validation of clinically relevant variants, the development of new cancer drugs, and the implementation of these new therapies into clinical treatment regimens,” Illumina said in a whitepaper published in November 2014 and available on its website.

Illumina added that it continues to collaborate with leaders of the Actionable Genome Consortium to set standards for NGS-based assays in routine clinical oncology practice, as well as to define regulatory frameworks to enable widespread use of NGS.

Illumina co-formed the consortium in September 2014 with four cancer research institutes—Dana-Farber Cancer Institute, Fred Hutchinson Cancer Research Center, MD Anderson Cancer Center, and Memorial Sloan Kettering Cancer Center.

Friday, March 06, 2015

As with most healthcare decision, patients cannot rely on the Internet and oncology providers need to guide patients as make decisions about personalized cancer medicine. [© Alexander Raths/Fotolia.com]

Researchers from the Dana-Farber Cancer Institute report that websites that market personalized cancer care services often overemphasize their stated benefits and downplay their limitations. Many sites also offer genetic tests whose value for guiding cancer treatment has not been shown to be clinically useful, according to the team’s study (“Marketing of Personalized Cancer Care on the Web: an Analysis of Internet Websites”) in the Journal of the National Cancer Institute.

"Internet marketing may be detrimental if it endorses products of unproven benefit," write the investigators.

Internet marketing of cancer-related gene tests is unregulated so there is wide variation in how these services are presented, posing a challenge for consumers and their physicians, notes Stacy Gray, M.D., a medical oncologist and investigator at the Dana-Farber Center for Outcome and Policy Research and first author of the paper that analyzes 55 websites marketing the services.

"We wanted to see if consumers are getting a balanced picture of benefits and limitations of these services," says Dr. Gray. "We found a lot of variation. Some of the information is good, but all of it needs to be looked at critically by consumers and health care providers."

The study found that "in general, the benefits of these personalized cancer products are reported much more frequently than are the limitations," continued Dr. Gray. In addition, 88% of the websites offered one or more "nonstandard" tests that lacked evidence of clear clinical utility in routine oncology practice.

The scientists analyzed personalized or precision cancer medicine (PCM) products and services marketed by private companies, academic medical centers, physicians, research institutes, and other organizations. PCM was defined by the authors as "...products or services that could be used to tailor, personalize, or individualize care based on genomic or tumor-derived data." PCM often refers to testing DNA from samples of a patient's tumor to detect mutations or other genetic abnormalities. The results may help physicians predict how the disease will behave and select a drug or drugs targeted to the particular mutations found in the cancer. Such targeted agents may be more effective and cause fewer adverse side effects than standard chemotherapy.

These somatic tests look at the genetic characteristic of the tumor itself. Germline testing analyzes the patient's personal genome  and may turn up altered genes in a healthy person that raise his or her risk of developing cancer.

A majority of the Internet sites (58%) offered somatic testing, and 20% marketed germline testing, the study found. In addition, 44% of sites offered some form of personalized cancer care.
The report cited examples of marketing claims such as:

"Reduce trial and error at the prescription pad. Genetic testing is a tool for better patient care, greater accuracy, lower costs, enhanced care-that is our promise."
Using the marketer's "enhanced treatment options, our patients experienced a greater life expectancy, often with less side effects than standard treatment." A late-stage pancreatic cancer patient's life "was extended five years by (our product)-guided treatment."
"Our laboratory analyzes your tumor's response to 8-16 drugs and combinations to identify which treatments will work best to kill your cancer."
Claims and other information posted on Internet sites are not subject to regulation by agencies such as the FDA or the Federal Trade Commission. More recently, the FDA has said it intends to begin regulating genomic testing more broadly.

Even if regulation of the websites becomes a reality, the researchers said, "Oncology providers will need to guide patients as they navigate decisions about personalized cancer medicine."

Sunday, March 01, 2015

The March issue of Clinical OMICs is available now! Check it out by clicking on the link below.

Clinical OMICs Volume 2, Issue No. 3

Jeffrey S. Buguliskis, Ph.D.

Sunday, March 01, 2015

Sequencing of RNA molecules, like the one pictured above, is a powerful laboratory discovery tool that has the potential to play a major role in clinical diagnostics. [Shutterstock/©petarg]

Advances in genomics over the past several years have had a profound impact on our grasp of molecular biology and genetics. In the laboratory, next-generation sequencing (NGS) has been applied to identifying novel genomes for an array of organisms, DNA resequencing, transcriptome sequencing, and epigenetics. Within clinical settings, NGS is beginning to cut its teeth and is being rapidly embraced as an invaluable diagnostic tool. Specifically, the ability to interpret the genetic mechanisms that underlie variations in human gene expression through the direct analysis of the transcriptome makes RNA sequencing (RNA-Seq) an attractive method to clinical diagnosticians. “RNA-Seq provides a very specific and sensitive genomic signature that can be useful in many clinical situations,” said Gary Schroth, Ph.D., distinguished scientist at Illumina.

RNA-Seq examines the dynamic nature of the cell’s transcriptome, the portion of genome that is actively transcribed into RNA molecules. While DNA remains relatively unchanged throughout an individual’s lifespan, RNA, in the form of transcriptional elements, can vary dramatically due to influences on epigenetic regulators, alternative spliced variants, or post-transcriptional modifications.

For the rest of the story, click here.

Sunday, March 01, 2015

More than 100,000 health and wellness mobile apps are now available, a 2014 report shows. [© alexey_boldin/Fotolia]

As mobile technology has become more powerful and ubiquitous, it was only logical to assume that health and medical apps reaching directly to the consumer could significantly change how healthcare is delivered. From applications that help patients self-monitor their diet to exercise and wellness apps, the public’s appetite for taking greater control of their health via their tablets and smartphones continues to grow. With more than 100,000 apps now available, a 2014 report by research firm Research2Guidance projects the mobile health app market will have produced $26 billion in revenue by the end of 2017, up from only a few billion dollars to date.

And while this consumer health revolution is plain for all to see, a similar revolution, lagging by perhaps only a few years, is picking up steam in the medical imaging and diagnostic field. Leveraging both the improved imaging capabilities of smartphones and their increased computing power, new screening and diagnostic tools that target cancer, kidney disease, and influenza, among a host of others, are showing significant promise in moving the diagnostic lab to remote locations and, in the process, significantly improving the health of the underserved.

For the rest of the story, click here.

Patricia Fitzpatrick Dimond, Ph.D.

Sunday, March 01, 2015

Most cases of colorectal cancer evade early detection, with about 50% of patients being diagnosed at advanced tumor stages. [© adrenalinapura /Fotolia]

More than 1.2 million new cases of colorectal cancer (CRC) occur glob- ally each year, resulting in about 600,000 deaths. CRC remains the third most commonly diagnosed cancer in both men and women in the United States; estimated new cases in 2015 will reach 132,700.

Unfortunately, the majority of CRC cases continue to elude early detection. About 50% of CRC patients are diagnosed at advanced tumor stages. Such patients have poor prognoses. Earlier diagnoses, and better prognoses, may be attained by means of early screening for CRC. Implementing such screening has become one of the greatest public health challenges over the last 50 years.

A means of reliably predicting gene expression profiles (GEPs) for those who will develop CRC has proven hard to develop. And questions about the ultimate clinical utility of predictive tests for Stage II patients who require chemotherapy remain, even as companies continue to introduce new tests.

For the rest of the story, click here.

Emil Salazar

Sunday, March 01, 2015

Prenatal testing offers technologies like sequencing, microarrays, and mass spectrometry, pointing to opportunities for growth in clinical diagnostics. [© Photographee.eu/Fotolia]

Family planning and coordination of care for a child born with health conditions are significant concerns for the in vitro diagnostics (IVD) community, which is increasingly involved in the prenatal testing market. While ethical con- siderations will arise with further market development, prenatal, postnatal, and maternal testing are viable, prom- ising cytogenetic screening methods that have seen ready acceptance from many insurers in at-risk populations where the prevalence of genetic disorders (especially chromosomal) justify coverage.

Prenatal cytogenetic testing represents an important source of clinical market growth for technologies such as sequencing, microarrays, biomarker immmunoassays, and mass spectrometry. Kalorama Information has reported extensively on prenatal testing markets for more than a decade, but recently there’s been an increase in activity, as revealed in our latest study of the women’s health diag- nostics markets.

For the rest of the story, click here.

Tim Durfee, Dan Nash, Ken Dullea, Jacqueline Carville, Marjorie Beggs, Jon Wilson, Chris Larsen, and Frederick R. Blattner

Sunday, March 01, 2015


As next-generation sequencing (NGS) makes genetic testing for a wide range of human diseases increasingly commonplace, facile methods for validating the efficacy of those tests are essential. Federal regulatory standards embodied in the Clinical Laboratory Improvement Amendments (CLIA), for instance, are designed to ensure that these tests reliably achieve certain performance specifications in terms of accuracy, precision, and analytical sensitivity and specificity.

To facilitate the test validation process, the National Institute of Standards and Technology (NIST) through the Genome in a Bottle Consortium (GIAB) developed a highly curated set of genome-wide reference materials for the HapMap/1000 Genomes CEU female, NA12878. These materials include BED and VCF files of high confidence sequence regions and variant calls, respectively. NA12878 genomic DNA and a cell line are available (Coriell Institute) providing laboratories with an internal control for their processing and analysis pipeline.

Comparing testing results to the GIAB call sets allows establishment of both the analytical performance for regulatory certification as well as the appropriate assembly thresholds to apply when considering potential variants in clinical samples.

For the rest of the story, click here.

Thursday, February 26, 2015

Genomic rearrangements may result in stable, locally rearranged, scattered, or unstable mutational landscapes in pancreatic cancer. [© Mopic/Fotolia]

Genomics meets gene tectonics in a pancreatic cancer study that describes large-scale genomic rearrangements that can be likened to geological events. In pancreatic cancer, large slabs of DNA can slide from one genomic region to another, changing the genomic landscape. While DNA fault lines and ridges have been exposed by whole exome analysis, the broader picture is emerging only now, with the application of whole genome analysis.

With the benefit of the whole genome perspective, which takes in the whole genome, not just the genome’s protein-coding sequences, four kinds of genomic rearrangement have been uncovered—“stable,” “locally rearranged,” “scattered,” and “unstable.” These four pancreatic cancer types roughly correspond to different degrees of genetic upheaval and account for the frequency, location, and types of DNA redisposition. For example, genes can be inverted, deleted, or multiplied. Also, genes can sustain damage, much like landforms can be scarred near geologic fault lines.

These findings appeared February 25 in Nature, in an article entitled, “Whole genomes redefine the mutational landscape of pancreatic cancer.” Besides recognizing distinct forms of pancreatic cancer, the article emphasizes that the newly found categories could be used to improve treatments for the disease. In the case of “unstable” genomes, treatment prospects seemed especially promising.

“We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs),” wrote the authors. “Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A, and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2).”

Besides pointing out four distinct pancreatic cancer subtypes, the authors noted that DNA rearrangements caused genetic chaos, with genes deleted, wrongly switched on and off, or entirely new versions created. Some of the genetic faults, however, are may be treatable with existing drugs. According to the authors, potentially druggable oncogenes include ERBB2, MET, FGFR1, CDK6, PIK3R3, and PIK3CA.

The study’s authors, which included scientists from Cancer Research UK and the Garvin Institute of Medical Research, also suggested certain pancreatic cancer patients could benefit from platinum-based drugs.

“Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2, or PALB2) and a mutational signature of DNA damage repair deficiency,” they reported. “Of eight patients who received platinum therapy, four of five individuals with these measures of defective DNA maintenance responded.”

The study’s co-lead, Professor Andrew Biankin, affiliated with both Cancer Research UK and Garvin, and currently at the University of Glasgow, indicated that being able to identify which patients would benefit from platinum-based treatments would be a “game-changing moment, potentially improving survival for a group of patients.” More generally, Professor Biankin added, “Our crucial study sheds light on how the chaotic chromosomal rearrangements cause a huge range of genetic faults that are behind the disease and provide opportunities for more personalized pancreatic cancer treatment.”

Wednesday, February 25, 2015

Source: © rob3000/Fotolia

Selah Genomics, a subsidiary of EKF Diagnostics, entered an 18 month collaboration with Greenville Health System (GHS), DecisionQ, and Becton Dickinson and Company (BD). The goal of the alliance is to unite clinical annotations with next-generation sequencing (NGS) technology and artificial intelligence-based algorithms in hope of improving clinical decision making for the treatment of colon cancer, according to the organizations.

Selah will utilize its PrecisionPath™ NGS technology to determine the genetic profiles of tumor samples provided by GHS’ Institute for Translational Oncology Research. The company said the samples, from colon cancer patients with known outcomes, will be provided with full clinical annotation. DecisionQ will employ its machine-learning platform to integrate genetic profile data with clinical annotations to produce a model of a clinical decision support tool. Funding for the research project is being provided in part by BD in return for the first opportunity to license the technology if the collaboration is successful. A clinical trial is planned to validate the research and affirm the effectiveness of the new system. After proving the value for colon cancer, EKF and Selah said they plan to continue to evaluate similar models on other sites of origin.

“This initial collaboration will demonstrate the power of a new generation of personalized medicine decision support tools for oncologists, starting with a particular focus on empowering oncologists treating colon cancer patients in the community-based setting,” said Michael Bolick, CEO, Selah Genomics. “Leveraging particular contributions from each of our partners, we have a unique opportunity to fast track our development timelines across an array of targets.”

U.K. based EKF Diagnostics bought Selah Genomics in April 2014 as part of a deal worth up to $75 million. Selah has a history of collaborating with GHS in oncology research. Three years ago, the company established a lab at GHS’ Institute for Translational Oncology Research to implement PrecisionPath in a clinical setting.

Friday, February 20, 2015

The FDA has granted 23andMe authority for marketing a direct-to-consumer genetic test, nearly a year and a half after forcing the company to stop selling its Saliva Collection Kit and Personal Genome Service® (PGS), and submit to agency review of its test as a medical device.

23andMe won authority to offer a Bloom syndrome carrier status test indicated for detecting the BLMAsh variant in the BLM gene, based on saliva collected using an FDA-cleared collection device, the Oragene DX model OGD-500.001. The test is designed to assess users’ carrier status for the rare inherited gene disorder, which is characterized by short stature, sun-sensitive skin changes, an increased risk of cancer, and other health problems.

However, the company cautioned that it will not immediately begin returning Bloom syndrome carrier status test results—or any other health results—to customers until it completes regulatory reviews for additional test reports, and thus can offer a more comprehensive product offering.

“This is a major milestone for our company and for consumers who want direct access to genetic testing," Anne Wojcicki, 23andMe CEO and co-founder, said in a company statement. “We have more work to do, but we remain committed to pursuing a regulatory path for additional tests and bringing the health reports back to the US market.”

In addition to giving its authorization, the FDA said separately it will classify carrier screening tests for autosomal recessive disorders as “Class II” devices, and will issue a notice announcing its intent to exempt these devices from premarket review, with a 30-day comment period.

“The FDA believes that in many circumstances it is not necessary for consumers to go through a licensed practitioner to have direct access to their personal genetic information,” Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health, said in an agency statement.

The statement also justified FDA’s actions as supporting innovation and ultimately benefiting consumers. The agency was accused by free-market advocates of trampling on both in November 2013 when it ordered 23andMe to stop selling its Personal Genome Service and directed the company to seek approvals for its test. The agency cited what it called the potential public health consequences of inaccurate results from the PGS device.

23andMe’s Bloom syndrome carrier status test was evaluated through the de novo regulatory pathway, designed as an alternate path to classify new devices of low to moderate risk that are not substantially equivalent to an already legally marketed device. The de novo pathway was created by the Food and Drug Administration Modernization Act of 1997 (FDAMA). 

While devices that are classified through the de novo process may be marketed and used as predicates for future 510(k) submissions, 23andMe said it submitted its  application for review under standard 510(k) requirements. Because the direct-to-consumer test being reviewed was the first-of-its kind, the FDA determined that 23andMe's submission did not have an applicable predicate device, and converted it to a de novo request.

23andMe said it met FDA premarket requirements by demonstrating accuracy, validity and user comprehension, since its “spit kit” and chip array platform were validated for determining whether or not an individual is a carrier for the genetic markers for Bloom syndrome.

23andMe said it conducted “extensive” comprehension studies with consumers from different backgrounds, education levels and incomes, as well as an accuracy study performed at two lab sites with 70 samples. The samples included sixty-five saliva samples and five human cell line samples with known BLMAsh variant status. Results of the PGS test for Bloom Syndrome were compared with sequencing results, showing agreement in all 70 samples.

Also carried out was a validation study in which 2,880 sample replicates were run under standard 23andMe lab procedures, followed by an additional study of 105 saliva samples without the BLMAsh variant. Samples were tested by comparing results between both lab sites.

In addition, a user comprehension study was performed to assess how well people understood the PGS Bloom syndrome carrier status test reports. A sample desuigned to be representative of the US population reviewed and answered questions about the test report in a moderator-controlled setting.  More than 90% of participants indicated they understood the test results, 23andMe said.

Thursday, February 12, 2015

Source: © drizzd/Fotolia.com

Whole genome sequencing (WGS) is well on its way to transforming medicine. However, there are a few bumps on the road that WGS needs to overcome before it can become a broadly used and increasingly effective tool for the clinic. Current limitations include the need for WGS tests to be more reliable, demonstrate a better ability to capture the entire genome, and improve its predictive capabilities, which right now hinder the task of interpreting the results.

This GEN webinar will focus on scientific, clinical, and patient-oriented strategies to help WGS meet its high clinical expectations. Topics to be covered include whole genome sequencing strengths and weaknesses, transitioning from exome sequencing quality concerns and clinical utility to complementary issues with WGS, patients’ views on costs vs. benefits of WGS, potential risks associated with discrimination resulting from WGS data, regulatory and reimbursement issues, and themes revolving around privacy and patient ownership of WGS data. During the webinar Dr. David Smith will also point out specific clinical indications for which whole genome sequencing might be appropriate, Dr. Jason Park will talk about the need for improved standards covering whole genome sequencing and other techniques used in genomic medicine, and James O’Leary will provide the patient’s perspective on whole genome sequencing in the clinic.

To view this webinar cick here.

Thursday, February 12, 2015

A collaborative team of scientists have developed a new whole-genome sequencing technique to detect spontaneous mutations in IVF embryos. [3dmentat/Fotolia]

Since the first in vitro fertilization (IVF) birth in 1978 more than 5 million babies have been born using this method. In order to alleviate added stress for couples already experiencing difficulties to conceive, fertility scientists utilize pre-implantation genetic diagnosis (PGD) techniques to detect large chromosomal abnormalities or gene mutations that are passed along by parents to the IVF embryos.      

Unfortunately, it is not possible to systematically scan the entire genome of the embryo in order to detect spontaneous mutations. However, scientists from Complete Genomics, Reprogenetics, and the NYU Fertility Center believe they may have solved that problem.

Scientists from the collaboration have developed a whole-genome sequencing method that uses 5- to 10-cell biopsies from the in vitro embryos to scan for potentially detrimental mutations.    
The results from this study were published online in Genome Research in an article entitled "Detection and phasing of single base de novo mutations in biopsies from human in vitro fertilized embryos by advanced whole-genome sequencing".

Investigators sequenced three biopsies from two IVF embryos and searched for de novo mutations, those that emerge spontaneously in the egg or sperm and are not inherited by parental genes. Spontaneous mutations are believed to play a significant role in many congenital disorders such as autism, epilepsy, and some severe forms of intellectual disability.  

"Because each individual carries on average less than 100 de novo mutations, being able to detect and assign parent of origin for these mutations, which are the cause of many diseases, required this extremely low error rate," said co-authors Brock Peters, Ph.D., director of research and Radoje Drmanac, Ph.D., CSO at Complete Genomics.

Typically, 5 to 10 cells are biopsied from the blastocyst embryo, and the DNA is amplified before sequencing is performed. Due to lack of replication fidelity, the amplification process introduces thousands of errors, many of which are determined to be spontaneous mutations, leading to a false positive result. The current method that the collaborative teams have developed, which uses long fragment read technology, was able to eliminate over 100,000 sequencing errors or a 100-fold reduction over currently used clinical methods.

Overall, the researchers were able to detect 82% of all de novo mutations in IVF embryos. Interestingly, they did not find any mutations within the protein coding regions from the genome of one embryo, but another embryo from the same couple yielded two coding mutations in the ZNF266 and SLC26a10 genes. Mutations within these genes have led to serious diseases and defects. However, the scientists noted that they are currently unaware if the specific mutations they observed would lead to any detrimental health issues for the fetus.   

"The biggest hurdle now is one of how to analyze the medical impact of detected mutations and make decisions based on those results," said Dr. Peters and Dr. Drmanac.

In addition to the benefits for IVF, the scientists feel that their methodology could be employed for other clinical applications where trying to obtain cells is a challenge such as circulating tumor cells or circulating fetal cells. 

Tuesday, February 10, 2015

Source: © Robert Mizerek/Fotolia.com

Roche has acquired Signature Diagnostics for an undisclosed price. The deal is designed to strengthen Roche’s cancer diagnostics effort with Signature’s expertise in both biobanks and next-generation sequencing (NGS) assays, and is the pharma giant’s fifth deal in less than a year focused on molecular diagnostics and data analysis.

Signature will be integrated into Roche’s Sequencing Unit and will continue to focus on expanding its genomic signature portfolio.

Founded in 2004, privately-held Signature is a translational oncology and genomics company that develops large blood plasma and tissue biobanks in multiple cancers—including colorectal and lung cancers—constructed from multicenter prospective clinical studies.

Signature uses the samples from its biobanks along with accompanying clinical progression and genetic data to develop and validate circulating cell free DNA (cfDNA) tests for research use only, with the goal of advancing non-invasive treatment response monitoring for patients with cancer. Signature also develops several NGS assays, which use targeted gene panels and are also for research use only.

“Signature represents a unique bridge between high value cancer biobanks and NGS assay development.  Roche plans to leverage Signature's expertise in both of these areas to accelerate the development of targeted NGS-based diagnostics in the future,” Roland Diggelmann, COO, Roche Diagnostics, said in a statement.

Added Andre Rosenthal, Ph.D., Signature’s CEO: “We are very pleased Roche recognizes the importance of high-quality longitudinal cancer biobanks for the development of novel NGS-based diagnostics.”

Signature is the fifth deal in the past year aimed at building Roche’s molecular diagnostics business. Last month Roche said it will take a majority stake in Foundation Medicine (FMI) for $1.18 billion, launching a personalized medicine partnership intended to help develop new Roche cancer drugs by harnessing FMI’s capabilities in molecular information and genomic analysis.

In December 2014, the pharma giant said it was acquiring Ariosa Diagnostics for an undisclosed price to enter the non-invasive prenatal and cell-free DNA testing markets. Ariosa is a San Jose-based molecular diagnostics testing service provider that offers non-invasive prenatal testing (NIPT) through their CLIA laboratory using cfDNA technology. The deal was completed earlier this year.

Six months earlier in June 2014, Roche acquired Genia Technologies for up to $350 million— $125 million cash upfront, plus up to $225 million in milestone payments—to, the developer of a single-molecule, semiconductor-based, DNA sequencing platform using nanopore technology. Roche said at the time that Genia’s sequencing technology held potential for disrupting the market by reduce the price of sequencing while increasing speed and sensitivity.

And in April 2014, Roche snapped up IQuum for $275 million upfront and up to $175 million in product-related milestones, with the intent of strengthening its offerings in molecular diagnostics. The acquisition provided Roche with access to IQuum’s Laboratory-in-a-tube (Liat™) System, which enables healthcare workers to perform rapid molecular diagnostic testing in a point-of-care setting.

Roche’s sequencing unit is part of its Diagnostics Division, which saw sales rise 6% in 2014 to CHF 10.766 billion ($11.678 billion), driven by increases in its professional diagnostics (8%) and molecular diagnostics (6%) segments.

John Sterling

Sunday, February 01, 2015

The GGC, founded in 1974, is organized to provide clinical genetic services, diagnostic lab testing, educational programs, and research in medical genetics.

In October, the South Carolina-based Greenwood Genetic Center (GGC) launched a whole exome sequencing (WES) program. The technique, carried out via next-generation sequencing, is particularly appropriate for patients who need additional genetic testing, e.g., chromosome analysis and single gene sequencing, beyond traditional approaches. Bioinformatics specialists analyze the results to help narrow down the hundreds or thousands of gene variants, hoping that a single mutation can explain a patient’s condition.

A group led by Charles E. Schwartz, Ph.D., director of research and head of GGC’s JC Self Research Institute, has been investigating genes associated with autosomal forms of intellectual disability (ID) and autism, utilizing clinical material available at GGC.

For the rest of the story, click here.

MaryAnn Labant

Sunday, February 01, 2015

Source: Khakimullin / Deposit Photos

Many factors drive the next-generation sequencing (NGS) market in regulated environments. Only a few years ago, the throughput and price point did not allow for easy transition from existing technologies. The launch of benchtop instruments has significantly reduced the capital equipment costs and simplified the skill sets required for operation, expanding common near-term applications in noninvasive prenatal testing (NIPT), oncology, virology, drug-resistance testing, and infectious disease.

Scientists from around the world gathered to discuss the changing dynamics of NGS at a VIB event, Revolutionizing Next-Generation Sequencing: Tools and Technologies, which took place January 15–16 in Leuven, Belgium.

For the rest of the story, click here.

Chris Anderson

Sunday, February 01, 2015

Clinicians devoted to precision oncology are as effective as their computational infrastructure is robust. [Rbhavana/Deposit Photos]

Whether they are concerned with a mutation of a single gene, or mutations in a combination of two or more genes, today’s oncologists look forward to using genomic information to more precisely target and treat cancer. But as more and more researchers delve into the work of discovering which genetic mutations are associated with specific subtypes of cancer, or which drugs are most effective in fighting the cancers identified by their signatures, they begin to test the limits of their informational tools—computing platforms, informatics packages, and analytic algorithms. These digital factors are driving (and sometimes hindering) advances in developing more precise and targeted therapies for individual cancer patients.

Many of today’s challenges to increasing the precision of cancer treatment are directly related to both the complexity of data generated by genetic sequencing and the sheer volume of biomedical information contained in the published literature detailing new discoveries in the root causes of cancer and the drugs and therapies that most effectively treat it.

For the rest of the story, click here.

Sunday, February 01, 2015

The February issue of Clinical OMICs is available now! Check it out by clicking on the link below.

Clinical OMICs Volume 2, Issue No. 2

Xing Wang, Ph.D., Zhenyu Sun, M.D., Xiaofeng Chen, M.D., Xiong Su, Ph.D., Gan Wang, Ph.D., and Matthew Kuruc

Sunday, February 01, 2015

Lung cancer is one of the most common malignancies and the leading cause of cancer-related fatality. In the United States alone, more than 210,000 new lung cancer cases are diagnosed every year, with more than 170,000 deaths resulting from the disease each year.

Current diagnostic practices for common cancers rely heavily on imaging technologies such as CT scans for lung cancer, mammograms for breast cancer, and pelvic ultrasounds for ovarian cancer. Given the high probability of false-positive findings associated with CT screening, there is a substantial need for additional noninvasive modalities to discriminate between benign and malignant nodules. There are similar challenges in imaging-based screening for other malignancies and a subsequent need for complementary diagnostic tests.

For the rest of the story, click here.

Alex Philippidis

Sunday, February 01, 2015

Increased scrutiny from the Office of Inspector General will force clinical labs to ensure that their practices are sound and their records complete. [WavebreakMediaMicro/Fotolia]

Washington will keep its eye on clinical laboratories this year—specifically, how much they are billing the federal government for services through Medicare.

The U.S. Department of Health and Human Services, through its Office of Inspector General (OIG), officially threw down the proverbial gauntlet to the labs in its Work Plan for the current federal fiscal year, which ends on September 30.

The Work Plan—the OIG’s annual report outlining its enforcement priorities for a given fiscal year—included for the first time “selected” independent clinical lab billing requirements.

For the rest of the story, click here.

Thursday, January 22, 2015

Source: © SSilver/Fotolia.com

A study, funded by the Movember Foundation and conducted by scientists at The Institute of Cancer Research (ICR) in London, has revealed several genetic mutations that may trigger the development of testicular cancer, in addition to uncovering a gene that may aid tumors in promoting resistance to existing drug therapies.

According to the authors, this is the first study of its kind to use whole-exome sequencing to probe testicular germ cell tumors, which constitute the majority of testicular cancer cases.

"This study has used the latest DNA sequencing technologies to provide a window into the development of testicular cancer, and reveals some potentially important clues as to how the disease could be treated more effectively,” stated Paul Workman, Ph.D., chief executive of ICR.

The investigators, whose research was published today in Nature Communications in an article entitled, “Whole-exome sequencing reveals the mutational spectrum of testicular germ cell tumours,” examined tumor samples from 42 patients with testicular cancer. They report previously unidentified chromosome duplications and confirmed data from earlier findings that associated these tumors with the KIT gene, which has been linked to an array of other cancerous tissues.

"Our study is the largest comprehensive sequencing study of testicular tumors published to date, describing their mutational profile in greater detail than has been possible using previous technologies,” says Clare Turnbull, Ph.D., senior author and  team leader in predisposition and translational genetics at ICR.

Interestingly, Dr. Turnbull and her team also found defective copies of the DNA repair gene XRCC2 in a patient who had become resistant to platinum-based chemotherapy. Their preliminary finding of a link between XRCC2 and platinum drug resistance was validated once they sequenced a sample from an additional platinum-resistant tumor. 

“We have identified new potential driver mutations for this type of cancer, and provided new evidence of a link between mutations in the gene XRCC2 and platinum treatment-resistant tumours. We now need additional studies with a larger number of patients, focusing in particular on platinum-resistant tumour’s, to help our discoveries lead to new options for those unlucky men whose cancer progresses in spite of the best available treatments," said Dr. Turnbull

Despite the fact that testicular cancer responds well to chemotherapy, about 3% of patients develop resistance to platinum-based drugs, which consequently is associated with a diminished long-term survival rate. This study provides essential general knowledge concerning testicular germ line cell tumor development, but more importantly, valuable insight into the genetic underpinnings as to why certain patients develop resistance to chemotherapy.

Thursday, January 15, 2015

Source: © Mopic/Fotolia

Scientists at the University of Michigan’s Comprehensive Cancer Center have uncovered genetic markers in a rare type of breast cancer called phyllodes tumors by wielding a powerful new tool in the molecular diagnostics arsenal: Next-Gen sequencing.

This comprehensive investigation of gene alterations, a first for phyllodes tumors, was published in the journal Molecular Cancer Research today under the title, “Next-Gen Sequencing Exposes Frequent MED12 Mutations and Actionable Therapeutic Targets in Phyllodes Tumors.”

While phyllodes tumors represent a small fraction (less than 1%) of breast tumors and are often benign, they are particularly aggressive in the their malignant state. Additionally, there are currently no reliable methods for predicting reoccurrence or malignant transformation after initial treatment. Nor are there many effective treatment options should malignancy occur.   

"We know little about the biology of phyllodes tumors” says principal investigator Scott A. Tomlins, M.D., Ph.D., assistant professor of pathology and urology at the University of Michigan Medical School. “In part, they have not been studied much because it's difficult to accumulate a large number of samples. Using these new sequencing techniques, we were able to study archived tissue samples, which allowed us to identify enough samples to perform a meaningful analysis."

Dr. Tomlins and his team obtained 15 samples of phyllodes tumors from the University of Michigan archives. These samples were dived equally in to three categories: benign, borderline, and malignant. Using Next-Gen sequencing, the researchers compared the phyllodes tumors samples against a panel of genes previously shown to have some functional role in other cancers.

The research team found two genes among the malignant phyllodes tumor set that were amplified, epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGFR1).  Due to their active role in other cancers, EGFR and IGFR1 have been a target for the development of a number of chemotherapeutic agents. The results from this current study would support assessing the currently available drugs in the treatment of phyllodes tumors.

In addition to the gene targets uncovered within the malignant tumor group, the investigators found a mutated gene, MED12, which was common in all three tumor sample categories. This gene has been shown previously to have a role in an array of cancer tissue types, but its occurrence in some rare gynecological cancers that are related to phyllodes tumors was of particular interest to Dr. Tomlins team. They suspect that MED12 could play a critical role in the tumor initiation step.   

“Taken together, this study defines the genomic landscape underlying phyllodes tumor development, suggests potential molecular correlates to histologic grade, expands the spectrum of human tumors with frequent recurrent MED12 mutations, and identifies IGF1R and EGFR as potential therapeutic targets in malignant cases.”

Tuesday, January 06, 2015

The January issue of Clinical OMICs is available now! Check it out by clicking on the link below.

Clinical OMICs Volume 2, Issue No. 1

Nicola Brookman-Amissah

Tuesday, January 06, 2015

Figure 1. On-Bead Post-Capture PCR Amplification Enhances Enrichment. Target capture was performed using xGen® Lockdown® Probes and SeqCap® EZ Hybridization and Wash Kit. Relative levels of three target genes after enrichment were measured by qPCR.

Scientists at Geneseeq Technology share how to improve target capture for accurate clinical diagnostics by using optimized blocking oligonucleotides and stringent hybridization conditions.

The diverse array of mutations contributing to cancer complicates the selection of effective treatment regimens. There are only several hundred genes that can be targeted for cancer treatment, and the current trend is to selectively sequence these. Personalized medicine is helping clinicians to make informed treatment decisions and is facilitated by the latest next generation sequencing (NGS) technologies.

Target capture is a more pragmatic alternative to whole genome sequencing that focuses on selected genomic regions and presents an ideal approach for the routine clinical application of NGS. However, this technique must be carefully optimized to ensure accurate data.

For the rest of the story, click here.

Sean Tunis, M.D.

Tuesday, January 06, 2015

The rapid development of NGS-based tests for use in oncology has highlighted this technology’s tremendous potential to improve clinical care and patient outcomes.

After many years of steady development in DNA sequencing, the scientific community is reaching an exciting threshold in understanding the genetic riddles behind cancerous tumors. Newly developing next-generation sequencing (NGS) techniques can rapidly analyze large quantities of DNA, offering a greatly enhanced understanding of the molecular complexity of disease. NGS promises to accelerate the understanding of cancer, helping to define tumors’ biological pathways and their genetic characteristics. It is already beginning to yield a more accurate picture of disease and making possible an expanding choice of targeted therapies. However, assessing the clinical utility of NGS-based testing, as well as the benefits and risks of off-label prescribing of targeted therapies, are complex and controversial issues.

For the rest of the story, click here.

Chris Anderson

Tuesday, January 06, 2015

FDA has concerns over the adequacy of the scientific evidence supporting the use of many laboratory developed tests. [Kasto/Fotolia]

If the tenor of the overflow crowd at November’s Association for Molecular Pathology (AMP) Annual Conference to hear FDA’s Alberto Gutierrez, Ph.D., is any indication, the agency’s move to tightly regulate laboratory developed tests (LDTs) faces an uphill battle to win over those who run the thousands of molecular pathology labs across the country. Dr. Gutierrez, director, office of in vitro diagnostics and radiological Health at FDA, noted the agency was legally provided with regulatory oversight of tests developed in labs in 1976. But based on the types of “homebrew” tests used at the time, the agency decided to exercise regulatory discretion regarding LDTs.

But things have shifted dramatically over the past 40 years as companion diagnostics have multiplied in number and molecular pathology labs now routinely search for specific genetic mutations and other markers to both identify specific subtypes of cancer and to suggest precision therapies.

For the rest of the story, click here.

Gabriel A. Bien-Willner, M.D., Ph.D.

Tuesday, January 06, 2015

Source: Nelsonart­/Deposit Photos

We recently tweeted an article about researchers from The Icahn School of Medicine at Mount Sinai who had identified a genetic variant that might predict how cancer patients respond to radiation. One of our Twitter followers pointed out that simply showing a correlation means nothing. He has a great point—there are thousands/millions of genetic variants that exist, but not all of them are actionable for cancer treatment.

There is a lot we don’t know about cancer. We don’t even have a rigorous definition of what malignancy is. Nonetheless, most of the medical community would agree that cancer is a genetic disease.

For the rest of the story, click here.

Patricia Fitzpatrick Dimond, Ph.D.

Tuesday, January 06, 2015

The prenatal diagnostics industry is expected to reach $3.6 billion by 2019 with the demand for prenatal tests tripling over the next six years. [Mopic/Fotolia]

Prenatal screening for detection of a wide range of monogenic disorders and chromosomal abnormalities has been available to prospective parents for over 40 years. But these screening techniques, including seroscreening and ultrasound, have false positive rates of 5% and 10–15%, respectively, requiring that 1 in 20 women face a decision of whether to undergo invasive testing that may include amniocentesis, chorionic villus sampling, or, rarely, cordocentesis.

All of these procedures involve some risk with fetal loss rates of approximately 1 in 300 procedures, according to the American College of Obstetricians and Gynecologists (ACOG).

But the discovery of circulating fetal DNA (cfDNA) in the maternal circulation and the development of advanced sequencing technologies have led some scientists and clinicians to predict that antenatal diagnosis will become a predominately noninvasive process that will usher in the era of noninvasive prenatal testing (NIPT).

For the rest of the story, click here.

Alex Philippidis

Tuesday, January 06, 2015

Lab reimbursement is going through major changes, both in terms of coding and reimbursement. [Ki33/Fotolia­]

Clinical laboratories will be watching and waiting in the new year for the Centers for Medicare and Medicaid Services (CMS) to resolve several unsettled issues concerning fees for molecular pathology tests, as well as coding for drug-screening tests.

CMS approved 21 new codes for advanced genomic studies such as exome sequencing and whole genome sequencing, as well as a range of hereditary and cancer/somatic mutation genetic panels.

However, CMS directed instead that they be set in 2015 via “gapfilling.” Local Medicare Administrative Contractors (MACs) will set fee schedule amounts during the first quarter of 2015, to be released for public comment. The contractors will submit final prices in or about August 2015, with CMS expected to publish the medians and set 2016 prices at those medians.

For the rest of the story, click here.

Emily Chen, M.D., Ph.D., Pim Suwannarat, M.D., Christine Kobelka, MSc and Gemma Chandratillake, MPhil, Ph.D., MS, LCGC

Wednesday, December 10, 2014

Source: © kentoh/Fotolia.com

Next-generation sequencing has facilitated an explosion in clinical genetic testing, and for some patients with unknown disorders for which there were previously no genetic tests available, exome sequencing is now an option. The enhanced variety of clinical genetic tests brings increasing complexity for clinicians. Selecting the specific genetic test that is most likely to inform a molecular diagnosis for a particular patient is nontrivial. Deciding when to order a gene-panel test versus an exome-sequencing test can be particularly challenging and has prompted the recent development of different algorithms to aid in such decisions. Much of the difficulty surrounding test selection is derived from technological limitations of exome sequencing.1 If such limitations can be overcome, decisions could be simplified significantly, with exome and whole-genome sequencing replacing the need for large gene panels. A company that provides a comprehensive clinical exome-sequencing test is California-based Personalis.

For the rest of the story, click here.

Rob Fraser, Ph.D., and David Huntsman, M.D.

Wednesday, December 10, 2014

David Huntsman, left; Robert Fraser, right.

With unprecedented scientific advances over the last decade in genome sequencing, we now have an opportunity to make genomics testing a standard practice in cancer care. The valuable genetic information that genome sequencing can deliver will alter the future of cancer care from the current singular treatment approach toward tailoring treatment to more precisely match a patient’s genomic profile.

The National Access Project for Cancer Testing, managed by the Personalized Medicine Initiative with testing provided by Contextual Genomics, is designed to drive and facilitate a paradigm shift toward personalized cancer care in which medication selection will be selected on the basis of a patient’s genetic tumor profile. Physicians, patients, pharmaceutical companies, payers, and healthcare systems are advocating for personalized medicine because there’s no question of the benefits it will bring to healthcare. What we will gain from this tailored treatment approach is better health outcomes, reduced adverse drug reactions, patient empowerment, and a major cost-savings on health care systems.

For the rest of the story, click here.

Chris Anderson

Wednesday, December 10, 2014

Diagnostic firms are working to create new tests that can detect rheumatoid arthritis earlier and also provide risk assessment profiles of patients that are more or less likely to suffer permanent physical damage as a result of the disease. [©Puwadol Jaturawutthichai/Shutterstock]

In oncology, more precise treatments for many different forms of cancer are in the offing, a prospect that makes oncologists the envy of other healthcare professionals. Already, cancer companion diagnostics can show doctors the specific drug that will be most effective in treating a particular subtype of cancer. Unfortunately, such specificity does not yet exist for diagnosing autoimmune diseases such as lupus, Sjogren’s disease, and rheumatoid arthritis.

More definitive diagnostics are needed for autoimmune diseases. Technologies capable of predicting drug responses would be especially welcome. But there are many development challenges: autoimmune symptoms are similar to symptoms of many other diseases; the disease pathways for many autoimmune disorders aren’t clear; and autoimmune diseases are systemic—unlike solid tumor cancers, which start as highly localized disease.

For the rest of the story, click here.

Harry Glorikian

Wednesday, December 10, 2014

Using NGS to detect cell-free DNA and other biomarkers could transform cancer care. [© Photographee.eu/Fotolia.com]

More than 40 years after President Nixon declared the War on Cancer in 1971, we are losing that battle. According to the American Cancer Society, 1.67 million new cancer cases will be diagnosed in the United States in 2014. About 586,000 Americans and six million people worldwide will die of cancer in 2014. Despite massive investments in treatment and prevention, cancer mortality among people under 85 in the United States has fallen a meager 8% since 1975. This has led many to wonder if our current strategy makes sense. As Einstein once said, insanity is doing the same thing over and over again and expecting different results. Will the “cure” for cancer come from more blockbuster drugs, or is the answer much simpler and now within our grasp?

Spending on cancer therapeutics is massive, with worldwide sales of $85 billion in 2013,1 and multiple drugs with $100,000 plus price tags on the market. However, on average, only a quarter of patients respond to any particular treatment—that’s a dismal response rate, and few of those are actual cures.2 This feverish focus on cures has dominated the research since President Nixon declared war on the disease in 1971. But the results are disheartening at best. As shown in Figure 1, this approach has yielded meager results; as mentioned earlier, the overall cancer mortality rate in the United States for ages younger than 85 years has fallen by a meager 8% since 1975. Heart disease deaths by comparison have dropped a whopping 60% or so—many times more than cancer deaths.

For the rest of the story, click here.

Alex Philippidis

Wednesday, December 10, 2014

Economic models for evaluating genomic data must consider both the costs and benefits of obtaining the data and delivering the treatments. [© Tameek/Fotolia]

2014 may have been the year the “$1,000 genome” became reality. But it’s ultimately a small piece of a much bigger
puzzle, the economics of genomic medicine and translating that value into actual health benefits to patients—that will continue to vex researchers and clinicians into the new year and beyond.

The falling cost of sequencing and other tools for extracting genomic data will be more than made up by the expenses labs and medical practices will face not only analyzing the growing deluge of raw data, but clinically interpreting those results. Yet genomic economics is also being shaped by factors beyond numbers—from data quality and quantity, to patient behavior, to the actions of payers.

“It’s not the cost of the test, per se, that’s going to be driving the economic decision making. It’s how the information is conveyed to providers and patients, and how they respond to it that is a first-order concern to an insurer, or someone thinking about implementing genetics in clinical practice,” John A. Graves, Ph.D., Assistant Professor at Vanderbilt University School of Medicine, told Clinical OMICs.

For the rest of the story, click here.

Patricia Fitzpatrick Dimond, Ph.D.

Wednesday, December 10, 2014

Trovagene has developed methods for isolation of the short, fragmented nucleic acids that pass through the kidneys and has created genomic and mutation panels offered through its CLIA-licensed lab. [LLEPOD/Deposit Photos]

Noninvasive molecular diagnostics based on cell-free DNA analysis are advancing as more methods have been developed to detect and quantitate nucleic acids from blood and urine. Recent studies suggest that genomic alterations in solid cancers can be characterized by massively parallel sequencing of circulating cell-free tumor DNA released from cancer cells, then excreted into urine or plasma.

Circulating tumor DNA (ctDNA) represents a promising biomarker for sensitive, specific, and dynamic detection of disease burden in cancer patients, investigators say. Additionally, ctDNA analysis allows noninvasive access to cancer genomes for tumor genotyping and monitoring of resistance mutations, enabling “liquid biopsy” from urine and plasma to assess tumor status.

For the rest of the story, click here.

Wednesday, December 10, 2014

MilliSect is a mesodissection instrument that enables efficient dissection from slide-mounted tissue for both clinical/research pathology and histology laboratories. [AvanSci Bio]

Roche Diagnostics signed a deal with AvanSci Bio to buy all products associated with the high- performance microdissection of slide-mounted tissue sections. The system consists of instrumentation, software, and consumables used by researchers and clinicians to extract specific areas of tissue with high precision and purity for subsequent molecular analysis including real time PCR, microarrays, and sequencing.

AvanSci Bio's technology includes the automated MilliSect™ instrument which reportedly enables a greater than 90% tumor enriched sample for molecular analysis. The system will be tested at select customer sites in 2015 as part of a broader development program for a future generation instrument.  MilliSect targets a 100mm2 to 100 µm2 level of resolution (what AvanSci refers to as " meso" dissection range).

"This innovative system will expand our diagnostic tool kit allowing us to link the diagnostic hematoxylin and eosin (H&E) stain with sequencing analysis through high quality sample preparation," said Dan Zabrowski, head of Roche Tissue Diagnostics and Sequencing Solutions. "It will also enable us to meet the critical challenge of tumor heterogeneity."

Tumor tissue staining gives researchers and clinicians important information about both tissue context and spatial relationships and tumor heterogeneity (which stems from the evolution of multiple subclones within the tumor). Information obtained from stained areas enable researchers and clinicians to pinpoint and extract more precise regions of interest within the tissue, resulting in purer samples of sufficient quantity that can then be used for sequencing. In addition, the analytical sensitivity of sequencing improves with higher sample purity as does subsequent data analysis and interpretation.

Tuesday, December 09, 2014

The fifteenth issue of Clinical OMICs is available now! Check it out by clicking on the link below.

Clinical OMICs Issue 15

Tuesday, December 02, 2014

© Voyagerix/Fotolia

Roche is acquiring Ariosa Diagnostics, a San Jose-based molecular diagnostics testing service provider that offers non-invasive prenatal testing (NIPT) through their CLIA laboratory using cell-free DNA (cfDNA) technology.

Ariosa’s Harmony Prenatal Test is designed to assess the risk of Down syndrome and other genetic abnormalities by evaluating fetal cfDNA found in maternal blood. Specifically, the test assesses the risk of trisomies 13, 18, and 21, which are indicative of an extra chromosome in the fetus that can lead to severe genetic conditions. Harmony has a less than 0.1% false-positive rate, according to the company.

“The acquisition of Ariosa is another example of Roche’s commitment to advanced molecular diagnostics,” said Roland Diggelmann, COO Roche Diagnostics Division. “Circulating cfDNA has the promise of providing early diagnostic information through a simple blood test in many important segments including pregnancy, cancer, and transplantation, aligning with our strategy in personalized healthcare and commitment to setting new standards of care.”

In April, Roche acquired IQuum to strengthen offerings in molecular diagnostics. The acquisition provided Roche with access to IQuum’s Laboratory-in-a-tube (Liat™) System, which enables healthcare workers to perform rapid molecular diagnostic testing in a point-of-care setting. 

Tuesday, November 25, 2014

© Monkey Business/Fotolia

Thermo Fisher Scientific and Samsung Electronics will jointly design, develop, and market new point-of-care (POC) solutions in key applications, such as the detection of sepsis, drugs of abuse, and therapeutic drug monitoring as well as the detection of cardiac problems and women’s health conditions.

“Samsung has developed a compelling and innovative suite of POC platforms,” said Marc Tremblay, Ph.D., president of Thermo Fisher’s clinical diagnostics business. “We look forward to working with Samsung to add some of our leading biomarkers and assays to their platforms to create a truly differentiated testing menu.”

“We are very excited to leverage Thermo Fisher Scientific’s strong commercial sales and service channels, as well as the potential to offer a broader range of tests to our customers and their patients,” said Soo-In Cho, president and head of the health and medical equipment business at Samsung. “This strategic collaboration combines the strengths of two industry leaders to accelerate POC innovation and more rapidly bring solutions to market.”

This year, Thermo has affirmed its personalized medicine ambitions. In September, the company entered an agreement with GlaxoSmithKline and Pfizer to develop a universal next-generation sequencing oncology test for solid tumors that will serve as a companion diagnostic for multiple drug programs. 

Wednesday, November 19, 2014

DxTerity’s goal is to make genomic testing a routine part of healthcare. Currently, costs are too high for standard use. DxTerity’s Dx Direct platform lets doctors run a wide variety of genomic tests from a single drop of blood at an affordable price.

Genomic technologies enabling relatively simple, rapid, and costeffective high-throughput testing of RNA-based multiplexed signatures in blood samples would greatly facilitate wide-scale adoption of molecular diagnostic tests in clinical medicine. Tests like CardioDx’ Corus CAD and CAREDx’ Allomap represent the first generation of products designed to improve diagnosis, predict therapeutic response, monitor drug responses in patients, and determine disease prognosis from a simple blood draw. This emerging class of tests known as IVDMIA tests is demonstrating value in clinical applications, and many researchers are developing assays with these methods.

One group of researchers, Shi et al., recently reported the development of blood-based, three-gene signatures for the noninvasive detection of early human hepatocellular carcinoma. These scientists used comprehensive gene expression profiling of purified RNA of peripheral blood mononuclear cells (PBMCs). Gene signatureswere developed through bioinformatics-driven approaches, and their diagnostic value was evaluated by custom-designed, quantitative, multiplex PCR assays.

But several factors including the technical complexity of current testing platforms, the high cost of materials and labor to perform them, and the limited availability of validated tests limit wide clinical use of RNA-based expression signatures. Other limitations include the need for RNA stabilization by freezing or by addition of a chemical denaturant that inactivates RNases. These chemical denaturants inhibit downstream amplification and assay methods.

For the rest of the story, click here.

Mary F. Lopez, Ph.D.

Wednesday, November 19, 2014

Figure 1. A BRIMS scientist connects up an ion source, which is often used in proteomics experiments.

Combining genomic and proteomic techniques can reveal important insights to unlock complex biological function. The exploration of methods for integrating large genomic and proteomic datasets is gaining traction due to improved bioinformatics and the public availability of well-organized, searchable data. Also, by merging RNA sequencing with mass spectrometry and improving bioinformatics, scientists can strategically select from a much broader range of investigational techniques and take advantage of complementary information. When one avenue of investigation closes, another may offer a new route to discovery—either building on previously inconclusive results or offering altogether new insights. Multiple studies in the past several years have demonstrated that transcriptional profiling data do not necessarily correlate with protein expression data, confirming that the two types of information are not duplicates but, instead, may be synergistic in terms of broadening our understanding of basic biology.1

In this brief overview, three recent examples illustrate how a “proteogenomics” approach can improve investigational power by enabling a progression of approaches that lead to actionable conclusions. When it comes to translational medicine, proteogenomics may provide better prospects for revealing biomarkers, assessing disease states, and identifying the complex mechanisms behind biological function (Figure 1).

For the rest of the story, click here.

MaryAnn Labant

Wednesday, November 19, 2014

Qiagen’s QuantiNova kits have a built-in tracking system for visual identification of correct pipetting.

The polymerase chain reaction (PCR), invented about three decades ago, soon entered mainstream use thanks to an ongoing series of refinements.

One particularly important refinement, introduced about two decades ago, is the “real time” quantification of DNA. The idea is to trace the rising level of DNA throughout the amplification step, and not just measure the final amount of amplified product. This idea turns standard PCR into real-time PCR, or quantitative PCR.

Real-time PCR has become the most widely used nucleic acid detection technology. It is routinely used in academic research, in applied testing settings such as food-safety or veterinary testing, and in molecular diagnostics. It continues to replace many older detection methods due to simple readouts, high sensitivity, and multiplex and quantification capabilities, as well as ease of use, cost effectiveness, and throughput flexibility with only moderate equipment investments.

According to Peter Urbitsch, Ph.D., head of the global assay technologies business at Qiagen, real-time PCR technology has evolved and diversified in multiple directions. Available formats include tubes, microarrays (96-, 384-, and 1,536-well plates), and capillary and rotor variants. Detection principles include SYBR green and probe-based detection, with the latter being increasingly diversified into FRET, Scorpions, TaqMan, and others. In addition, multiplex detection formats are being developed using different dyes and quencher molecules.

For the rest of the story, click here.

Jeffrey N. Gibbs

Wednesday, November 19, 2014

© Alexander Raths - Fotolia.com

On July 31, the Food and Drug Administration (FDA) notified Congress that it intended to issue two draft guidances regulating Laboratory Developed Tests (LDT’s). See our previous coverage. While the Energy and Commerce Committee House Subcommittee on Health did hold a hearing on September 9, Congress took no steps to block the issuance of the documents. On October 3, 67 days after notifying Congress, FDA published the proposal in the Federal Register.

The documents released on October 3 differed in only two minor respects from the proposals provided to Congress. Reflecting the significance of these documents (and also to avoid conflicts with the holidays), FDA did provide a 120-day comment period, which is longer than usual for guidance documents.

In releasing the draft guidance documents, FDA asked commenters to specifically address certain topics. Even before releasing the documents for comments, FDA had received initial feedback from various parties. Presumably, the areas which FDA highlighted will be ones for which the agency is particularly receptive to modifying its proposal.

For the rest of the story, click here.

Kate Marusina, Ph.D.

Wednesday, November 19, 2014

Illumina’s MyGenome App for iPad simplifies visualizing and exploring the human genome.

The explosive growth of DNA-based diagnostics empowers us to take a closer look at our own health and to demand answers from healthcare providers to questions that have never been asked before. Even if we do not fully understand the clinical relevance of most of the genetic changes, the information that has been validated is significant enough to change the status quo of medical care.

It is only natural that mobile devices are tapped for their unprecedented power and flexibility to deliver physiological data and lab results when and where it is needed most. As the maturing world of mobile devices meshes with the rapidly emerging word of genomics and biosensors, medicine could literally be found at our fingertips. This powerful combination not only gives more tools to treat the existing conditions but could also shift medicine into a true preventative mode.

Some visionaries hypothesize that mobile data will eventually lead to the demise of brick-and-mortar hospitals. One such visionary, geneticist and cardiologist Eric Topol, M.D., advocates the widened use of wearable, wirelessly networked biosensors to advance personalized medicine. In his popular book, “The Creative Destruction of Medicine,” Dr. Topol even anticipates that digital tools could empower a consumer-led democratization of medical care.

For the rest of the story, click here.

Chris Anderson

Wednesday, November 19, 2014

© Alexander Raths - Fotolia.com

Since the development of the first companion diagnostic for Herceptin was introduced more than 10 years ago, the development paths for these tests have followed the same formula: stratify patients by identifying a single marker that can predict the likelihood that a single therapeutic will or won’t be an effective form of treatment.

From a clinical standpoint, a companion diagnostic (CDx) seeks to close the gap between a “one size fits all” approach to using a drug and a tailored approach to using the drug in an individual patient. The bulk of the companion diagnostics available for clinicians target oncology drugs and have been developed as researchers have come to better understand the mechanisms, pathways, and manifestations of cancer, all helping to answer the age-old conundrum of why certain patients respond to therapy while others show no improvement.

In short, a companion diagnostic helps clinicians determine the safest and most effective use of a drug for only those patients who stand to benefit from it. On the flip side, it also helps avoid unnecessary treatment for patients who won’t respond, which allows doctors to seek alternate treatment routes right away—an especially important consideration for oncologists to avoid wasting time on ineffective treatment. A CDx test can also help identify patients that may have a significant adverse reaction to a drug.

For the rest of the story, click here.

Wednesday, November 19, 2014

The fourteenth issue of Clinical OMICs is available now! Check it out by clicking on the link below.

Clinical OMICs Issue 14

Thursday, November 13, 2014

© WavebreakmediaMicro - Fotolia.com

ARUP Laboratories will join the PierianDx partner network to share tools, assays, and clinical information in an initiative to improve the personalized interpretation of next-generation sequencing (NGS) clinical diagnostic tests.

ARUP will use PierianDx’s workflow management tools and NGS knowledge base to more effectively and quickly access its own knowledge base of variants and clinical outcomes, as well as benefit from the collective insights of other institutions in the PierianDx partner network, the company said. PierianDx offers a bioinformatics platform, workflow solution and software, and clinical information from thousands of previous genomic tests.

“Our expectation is that by leveraging PierianDx’s visionary software and database, we will be able to more effectively learn from past assays and provide even more personalized recommendations to physicians so they can better match their patients to the right therapies,” said Edward Ashwood, M.D., president and CEO at ARUP.

“By teaming with ARUP, the PierianDx partner network will benefit from insight provided by ARUP clinical interpretations, variants, and related de-identified patient information,” said Ted Briscoe, CEO. “All of our partners will be able to leverage our expanding knowledgebase to improve personalized diagnosis and care.”

ARUP offers more than 3,000 tests and test combinations, ranging from routine screening tests to highly esoteric molecular and genetic assays. Last month, ARUP announced that it was offering high-resolution HLA genotyping by NGS under an agreement with the Children’s Hospital of Philadelphia. In July, ARUP signed an agreement with University Hospitals Case Medical Center to distribute the DEEPGEN™ HIV test.

Jonathan Frampton, Ph.D.

Wednesday, November 05, 2014

Figure 1. Potential for variability in molecular diagnostics workflow

Companion diagnostics are bridging the gap between molecular diagnostics and therapeutics, helping to ensure that the right drug is provided to the right patient at the right time. Personalized medicine, with the aid of molecular diagnostics, is providing the exciting possibility of the delivery of cost-effective tailored therapies, based on an individual patient’s genetic code. This is particularly true in the case of cancer.

When applied correctly, companion diagnostics can help identify not only patients who are most likely to benefit from a particular therapeutic product, but also those likely to be at increased risk for serious side-effects as a result of treatment. Accurate diagnostics can also monitor response to treatment with a particular therapeutic product, to achieve improved safety.

As of October 2014, there were 19 FDA-authorized companion tests being used to support decisions on the particular therapy that a patient receives.

For the rest of the story, click here.

Alex Philippidis

Wednesday, November 05, 2014

PROMPT, an online registry for patients who have undergone hereditary cancer testing, is being developed by Ambry Genetics and several institutional partners.

The “Father of Modern Medicine” is also the father of patient registries. Hippocrates (c. 460 BC–c. 370 BC) urged doctors to record the symptoms they observed daily in their patients: “The physician must be able to tell the antecedents, know the present, and foretell the future.” (Of the Epidemics, c. 400 BC).

The first modern registries, focused on patient populations with specific diseases, emerged in the 20th century, with their use expanded for disease- and drug-based research by the 1980s. Now, in the age of Big Data, the registries give new meaning to community organizing by growing, or planning to grow, into sources of some of the most valuable data around—namely, the experiences of patients, and the genetics behind them.

For the rest of the story, click here.

Kathy Liszewski

Wednesday, November 05, 2014

One of the major roadblocks to successful biomarker development is an inadequate specimen procurement process. [Science Photo/Fotolia]

Tailoring healthcare decisions based on biological information represents the promise of personalized medicine. A key hurdle slowing progress toward tailored therapeutics is developing appropriate biomarkers for diagnostics, prognostics, and prediction.

Despite much research, only a trickle of biomarkers has made it into clinical practice. Researchers, however, are pursuing novel avenues and making headway by dissecting the subtle architecture of normal versus cancerous cells. New approaches include scrutinizing aberrant glycans, microRNAs shed from tumors, and epigenetic modifications, as well as mining and merging the vast stores of multi-omics data.

For the rest of the story, click here.

Wednesday, November 05, 2014

The thirteenth issue of Clinical OMICs is available now! Check it out by clicking on the link below.

Clinical OMICs Issue 13

Wednesday, November 05, 2014

Source: © vittavat - Fotolia.com

Roche said today it will establish a CHF 450 million ($467.2 million) diagnostic manufacturing facility at China’s Suzhou Industrial Park, the pharma giant’s eighth worldwide and first in the Asia-Pacific region.

The facility – set to become fully operational by 2018 – will focus on producing immunochemistry and clinical chemistry tests and will grow its workforce to more than 600 people “over the next several years,” Roche said.

“The new manufacturing site will enable us to meet the growing demand for our diagnostic products, ensuring our continuous contribution to the health of people in China and the Asia Pacific region,” Roland Diggelmann, COO of Roche Diagnostics, said in a statement.

Roche now employs more than 4,000 people in 15 countries across the Asia-Pacific region, where it has had a presence for 40 years. In China, Roche became the first foreign-based pharma giant to open a drug-discovery research center in 2004 at Zhangjiang Hi-Tech Park.

This year, the region has generated the fastest growth for Roche Diagnostics, with first-half 2014 sales rising 15% over the first six months of 2013, to CHF 877 million ($910.4 million). Asia-Pacific sales growth reflected in part demand for professional diagnostics.

“The sales increase in Asia–Pacific was also influenced by increasing sales in China (+24%) coming from governmental healthcare investments, public demand and the division’s expanding presence and wide portfolio,” Roche stated in its Half-Year Report 2014, covering January-June results.

While a Roche sales office in Hangzhou was “visited” earlier this year by local authorities investigating the practices of multinational pharmas, the company has not experienced the official wrath visited upon GlaxoSmithKline, which in September was fined almost $500 million by a Chinese court that meted out prison sentences to five of its former executives.

Roche also strengthened its Asia-Pacific presence last year by launching a partnership with Ascletis to develop and commercialize Roche’s investigational small-molecule NS3/4A protease inhibitor danoprevir in China for Hepatitis C virus. Ascletis agreed to fund and oversee development, regulatory affairs and manufacturing of danoprevir in greater China – including Taiwan, Hong Kong and Macau – in return for an undisclosed amount of development and commercial milestone payments from Roche, plus royalties.

Patricia Fitzpatrick Dimond, Ph.D.

Wednesday, November 05, 2014

The NCI is funding research to determine whether outliers from failed clinical trials can reveal hidden drug development possibilities. [francisblack/IStock Photos]

We have all heard stories about the single patient who survives a deadly cancer in response to a particular drug, in contrast to other patients receiving the same drug who succumb to the disease.

These patients may include heavily pretreated cancer patients for whom other drugs have failed, but then who respond to a therapy not typically used to treat their type of cancer. Now, with novel genomics tools at their disposal, investigators say that by analyzing the drug responses of “n-of-1,” patients who are single outliers in clinical studies, new insights into cancer mechanisms and more effective treatments can be gained. 

For the rest of the story, click here.

Thursday, October 23, 2014

Source: © mangostock - Fotolia.com

The University of Oxford is partnering with the Chan Soon-Shiong Institute for Molecular Medicine (CSSIOMM) to establish the first center in the U.K. designed to support the delivery of individualized, data-driven molecular-based medicine for NHS cancer patients. The new center, dubbed the Chan Soon-Shiong Oxford Center for Molecular Medicine (CSSOCMM), will be collaborating with the Oxford University Hospitals NHS Trust. 

The Chan Soon-Shiong Institute is initially investing $50 million to advance clinical cancer care in the U.K. through genomic and proteomic-driven diagnoses. These funds, CSSIOMM says, will provide doctors with large-scale sequencing capabilities for patient-level genomic, epigenomic, proteomic, and digital pathology data capture as well as tools and supercomputing technology to help clinicians make decisions regarding cancer treatments.

The CSSOCMM will be co-located with a new Precision Cancer Medicine Institute also announced today, where the clinical applications of its research will happen. It will also have links with the Target Discovery Institute and Big Data Institute, all of which are a part of an investment in cancer diagnosis and treatment being made by the University of Oxford over the next five years.

"Along with the University of Oxford, we are living our commitment to clinicians and patients alike," commented Patrick Soon-Shiong, M.D., founder and chairman of CSSIOMM, in a statement. "Using the most advanced, sophisticated tools imaginable, we’re on a mission to solve the mystery of cancer, and establish an adaptive learning system where the power of one can inform many."

"This investment highlights the international confidence in the UK’s ability to develop better and more personalized cancer treatments that can make a real difference to patients—especially in rare disease and cancer," George Freeman, the U.K.'s Minister for Life Sciences, commented about the announcement at a press conference in London. "The Prime Minister and I are determined to make Britain the best place in the world to discover and develop 21st century medicines."

This is CSSIOMM's third partnership this year; the Providence Health System and Phoenix Children's Hospital have also received CSSIOMM grants within the past six months.

Thursday, October 23, 2014

Source: © Dana Britton - Fotolia.com

Akers Biosciences inked a joint venture agreement with Hainan Savy Investment Management to research, develop, produce, and sell certain Akers’ rapid diagnostic screening and testing products in China. The joint venture company will be located in Haikou and incorporated as Hainan Savy Akers Biosciences.

As part of the agreement, the companies plan to market and sell the majority of Akers’ product line, with a special emphasis on diabetes, cardiac, and infectious diseases rapid diagnostic screening and testing products.

The headquarters will be located in the Haikou National Hi-Tech Industrial Zone and a manufacturing operation will be established in the same area.  The business will be structured to utilize numerous government incentives intended to develop and promote the Chinese diagnostic industry.  Other market opportunities in Asia will also be explored, the companies said.

Akers offers several diagnostic screening and testing products internationally, including its Breath Ketone test for diabetic monitoring, CHUBE disposable breath alcohol detectors, Tri-Cholesterol test, and particle immunofiltration assay based tests for infectious diseases such as chlamydia, dengue fever, malaria, and syphilis.

Chris Anderson

Wednesday, October 22, 2014

The power of new sequencing technologies is their ability to unlock information about the variable nature of solid tumors to provide clinicians with a better understanding of cancer’s mechanisms. [© Monika Wisniewska/Fotolia]

There is little doubt that the future of solid tumor cancer treatment will be increasingly precise and tailored to individual patients based on specific predictive biomarkers. Next-generation sequencing (NGS) technologies, which have become more refined in just the past few years, are a leading breakthrough that has allowed researchers and molecular pathologists alike to shift from querying single genes to panels that can simultaneously examine 40, 50, to even hundreds of genes in one run.

This is not to say that NGS will be the silver bullet of personalized cancer treatment, as there is a wide array of genetic tests available today to predict the risk of developing specific cancers and ones that also help target specific therapies to cancer subtypes. Rather, the power of these new sequencing technologies will be to unlock information about the variable nature of solid tumors to help provide clinicians with a better understanding of cancer’s mechanisms. Using this information, they can choose from the rapidly expanding roster of cancer therapeutics, specifically which one is most appropriate to best treat an individual patient based on the genetic profile of their cancer.

For the rest of the story, click here.

Patricia Fitzpatrick Dimond, Ph.D.

Wednesday, October 22, 2014

One novel technique for capturing clinically important low-abundance proteins is to create core-shell hydrogel nanoparticles containing high affinity reactive chemical baits for protein and peptide harvesting and concentration. [AlexRaths/iStock Photos]

Many scientists point out that it’s become clear there are no simple universal strategies for the comprehensive analysis of complex proteomes. Although the application of omics technologies to biological samples generates hundreds to thousands of biomarker candidates, a small number actually make it through the pipeline to clinical use, largely due to the incredible mismatch between the large numbers of biomarker candidates and the paucity of reliable assays and methods for validation studies.

Currently, the main technology platform for systematically interrogating large numbers of proteins is based on multiple reaction monitoring (MRM) mass spectrometry (MS). However, a substantial challenge in using MRM-MS for targeted peptide analysis in clinical proteomics applications is the prevalence of interfering peptides and small molecules in the sample matrix. This problem, although well studied for small molecule analysis, is both less well recognized and far more severe for peptide analysis because peptide MRM analyses are typically carried out in an ocean of many hundreds of thousands to millions of peptides produced by digestion of the 10,000 or more proteins found in blood and other tissues.

For the rest of the story, click here.

Summer E. Allen, Ph.D.

Wednesday, October 22, 2014

The predicted secondary structure of peptide p5+14. The peptide is alpha helical with all the charged lysine residues on one face of the helix. [University of Tennessee]

Researchers are developing a host of new uses for molecular imaging techniques—including magnetic resonance imaging (MRI), positron emission tomography (PET), and single photon emission computed tomography (SPECT)—that are already commonly used in patient care. Once these techniques have picked up new capabilities in the laboratory, they will return to the clinic, where they will likely transform the diagnosis and treatment of cancer and other diseases.

“The approval rate for new therapeutic entities in oncology is the lowest of all disease areas. Ninety percent of new chemical entities that go into clinical testing for cancer fail—despite the fact that they are all backed with tons of animal data suggesting that they should work,” says Andrew Kung, M.D., Ph.D., director of pediatric hematology, oncology, and stem cell transplantation, New York-Presbyterian Morgan Stanley Children’s Hospital/Columbia University Medical Center.

Dr. Kung has been at the forefront of a movement to improve preclinical animal studies—primarily by using more representative animal models of cancer and by measuring treatment response using molecular imaging and other techniques that might also be used to measure desired responses in patients.

For the rest of the story, click here.

Barbara M. O'Brien, Edward M. Kloza, Jacquelyn V. Halliday, Geralyn M. Lambert-Messerlian, and Glenn E. Palomaki

Wednesday, October 22, 2014

Researchers have found a growing understanding and acceptance by pregnant women of ccfDNA testing. [© igorborodin/ Fotolia]

In October 2011, the Sequenom Center for Molecular Medicine (SCMM) became the first laboratory in the United States to offer next-generation sequencing of circulating cell-free (ccf) DNA testing for Down syndrome (trisomy 21). This commercial launch followed the publication of an external clinical validation study demonstrating that testing could identify 98.6% of fetuses with Down syndrome (209/212) with a 0.2% false-positive rate (FPR) (Palomaki et al., 2011). In a later publication derived from that same high-risk cohort, 100% cases of trisomy 18 interpreted (59/59) were detected (FPR=0.28%) as were 91.7% (11/12) cases of trisomy 13 (FPR=0.97%) (Palomaki et al., 2012). Less than 1% of samples failed testing, including both case and control samples.

This level of performance is much better compared with the existing serum screening tests, offering the potential to reduce the number of invasive procedures (chorionic villus sampling [CVS] or amniocentesis) among high-risk women substantially, while maintaining detection of these common trisomies. The American Congress of Obstetricians and Gynecologists has recommended that women, regardless of age, be offered prenatal assessment for aneuploidy by screening or invasive prenatal diagnosis (ACOG, 2007). However, ccfDNA testing is currently recommended as a secondary screening test in women already identified at increased risk of aneuploidy (ACOG, 2012). Our prenatal diagnostic center planned on routinely offering ccfDNA testing to high-risk women receiving genetic counseling and sought to document implementation issues and women's decision-making encountered in the early introduction of this technology.

For the rest of the story, click here.

Naomi O’Grady

Wednesday, October 22, 2014

Source: © Mopic - Fotolia.com

The application of genomics in cancer has led to an improved understanding of the disease. To date, 125 driver genes have been discovered—71 tumor suppressors and 54 oncogenes—that promote tumor growth through 12 cellular signaling pathways.1 These pathways have become the focus of small molecule inhibitor drugs, primarily targeting kinases. While the number of available targeted therapies is limited, more than 800 oncology drugs are in development, many of which are designed to target specific mutations.2

Yet, the tumor genomic landscape is heterogeneous and researchers are finding that it evolves as cancer progresses. While single-analyte companion diagnostics exist, they require investigators to assay each target sequentially. The process is costly, time consuming, and in many cases exhausts the limited tissue available for analysis.

For the rest of the story, click here.

Wednesday, October 22, 2014

The twelfth issue of Clinical OMICs is available now! Check it out by clicking on the link below.

Clinical OMICs Issue 12

Friday, October 10, 2014

Source: © Sebastian Kaulitzki - Fotolia.com

Precision cancer therapy firm Perthera is partnering with the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and the Northwestern Medicine Developmental Therapeutics Institute (NMDTI) to conduct a translational research program aimed at assessing the utility of integrating next-generation sequencing, proteomic, and phospho-proteomic data in oncology developmental therapeutics and clinical practice. Under the alliance, the three organizations plan to develop clinical protocols incorporating Perthera's approaches and methodologies to cancer protocol treatment and to assess their impact on overall disease management and patient outcomes.

Perthera provides molecular diagnostic testing, profiling, and analysis services to create an analysis of a patient's individual cancer. The firm says it pairs proteomics with genomic analysis in the context of patient history to help oncologists identify personalized options for treating individual patients.

Lurie Cancer Center director Leonidas C. Platanias, M.D., Ph.D., said in a statement that the center—which says it is one of only 41 NCI-designated "comprehensive" cancer centers in the U.S.—considers this alliance with Perthera an important component of its focus on applying personalized medicine at both the individual patient and research protocol levels. "The rapid identification of cancer drivers and the attendant continuous expansion of our pipeline of cognate therapies that are directed at these targets is a major focus within our institutes," added Francis J. Giles, M.D., associate director for translational medicine and developmental therapeutics at the Lurie Cancer Center and director of the NMDTI.

The Lurie Cancer Center and NMDTI aren't the only institutions that have expressed interest in Perthera over the past year: Last June, the Pancreatic Cancer Action Network partnered with Perthera to identify relevant pathways and mutations for pancreatic cancer including previously unidentified targets.

Friday, October 10, 2014

Total Glut4 glucose transporter (left, green) and cell-bound Glut4 (right, red). Cell-bound Glut4 is increased in presence of insulin and a FAHFA lipid. [Weill Cornell Medical Center, Salk Institute and Beth Israel Deaconess Medical Center]

An exhaustive analysis of fatty acids from a diabetes-protected animal model has revealed a whole new class of molecules. These molecules, dubbed fatty acid hydroxyl fatty acids, or FAHFAs, enhance insulin sensitivity and glucose control. Better yet, they also reduce inflammation.

Ordinarily, elevated fatty acids are associated with insulin resistance and glucose intolerance, which in turn are associated with diabetes and metabolic disease. Yet elevated FAHFAs have been found to account for enhanced insulin sensitivity and improved glucose control in a specially engineered mouse strain. FAHFAs thus join a small collection of beneficial fatty acids alongside the omega-3 fatty acids.

Unlike the omega-3 fatty acids, which are found in fish oil, the FAHFAs are made in mammals. In fact, they are found in fat cells as well as other cells throughout the human body. FAHFA levels can even be detected in the blood.

All of these facts auger well for therapeutic development, say the researchers who discovered the FAHFAs. These researchers were led by Barbara Kahn, M.D., vice chair of the Department of Medicine at the Beth Israel Deaconess Medical Center (BIDMC) and the George R. Minot Professor of Medicine at Harvard Medical School, and Alan Saghatelian, Ph.D., a professor in the Clayton Foundation Laboratories for Peptide Biology at the Salk Institute.

“FAHFAs [are advantaged] in terms of therapeutic development because we can potentially modify the rate of production and breakdown throughout the body,” said Dr. Kahn. “Because we can measure FAHFA levels in blood, low levels may turn out to be an early marker for the risk of developing type 2 diabetes. Consequently, if restoring FAHFA levels in insulin resistant individuals proves to be therapeutic, we may potentially be able to intervene before the development of frank diabetes.”

“These lipids are amazing because they can also reduce inflammation, suggesting that we might discover opportunities for these molecules in inflammatory diseases, such as Crohn’s disease and rheumatoid arthritis, as well as diabetes,” added Dr. Saghatelian.

The scientists presented their finding October 9 in the journal Cell, in an article entitled “Discovery of a Class of Endogenous Mammalian Lipids with Anti-Diabetic and Anti-Inflammatory Effects.”

“Mice overexpressing the Glut4 glucose transporter in adipocytes have elevated lipogenesis and increased glucose tolerance despite being obese with elevated circulating fatty acids,” wrote the authors. “Lipidomic analysis of adipose tissue revealed the existence of branched fatty acid esters of hydroxyl fatty acids (FAHFAs) that were elevated 16- to 18-fold in these mice.”

The lipidomic analysis relied on mass spectrometry technology to quantify hundreds of lipids from biological samples. Four of these lipids turned out to be of particular interest because they were elevated in the engineered mice but not in normal mice. Although they could not be found in the existing databases the scientists consulted, their structures were ultimately elucidated via tandem mass spectrometry (MS/MS) and confirmed via chemical synthesis.

Molecules in the FAHFA family, the researchers found, consist of a hydroxyl fatty acid and another fatty acid that are joined by an ester bond: “FAHFA isomers differ by the branched ester position on the hydroxy fatty acid (e.g., palmitic-acid-9-hydroxy-stearic-acid, 9-PAHSA).”

Additional experiments revealed that feeding the mice extra FAHFAs resulted in a rapid and dramatic drop in blood sugar and rise in insulin. They also looked at FAHFA levels in human fat and plasma, studying samples from individuals who were known to be insulin resistant and at high risk for developing diabetes. In this case, FAHFA levels were found to be 50–75% lower than levels in people with normal insulin sensitivity, suggesting that changes in FAHFA levels might be contributing to diabetes.

The researchers also identified GPR-120, the cellular receptor that FAHFAs bind to. “When FAHFAs bind to GPR-120, they are able to control how much glucose is taken up into fat cells,” explained Dr. Kahn. The receptor may also be responsible for the effects of the novel lipids to reduce widespread macrophage activation, which is associated with obesity and with inflammatory diseases.

“The discovery of FAHFAs provides important new insights underlying metabolic and inflammatory diseases, and offers viable new treatment avenues that we hope to be able to test in clinical trials,” emphasized Dr. Kahn. “This is of critical importance as rates of obesity and type 2 diabetes remain at epidemic proportions worldwide.”

Thursday, October 09, 2014

Source: © uwimages - Fotolia.com

Roche has picked up exclusive rights to AbVitro's primer extension-based target enrichment (PETE) technology and associated patent applications AbVitro has filed. The technology, Roche says, will be used to support next-generation sequencing (NGS) directly from blood or other biological samples—something that could be a boon for clinicians.

Roche plans to incorporate PETE technology into its Sequencing Unit R&D pipeline to support the strategy of providing a full NGS workflow solution for clinical sequencing. Per the agreement, scientists from both firms will be teaming up to develop the technology.

"Sequencing is transforming the understanding among researchers and clinicians of how genomics will impact health," Dan Zabrowski, head of Roche Tissue Diagnostics and the Sequencing Unit, said in a statement. "We look forward to advancing this technology in order to streamline sequencing methods for easy-to-use clinical applications."

Therapeutic target discovery company AbVitro has a technology platform that the firm says can leverage natural immune responses to address diseases with unmet medical needs. This platform was based on technology developed by George Church, Ph.D., at Harvard Medical School.

"It is wonderful to see another potentially transformative sequencing technology transition into Roche where it can impact our daily lives," Dr. Church commented.

Enal Razvi, Ph.D.

Wednesday, October 08, 2014

As omics technologies continue to migrate toward clinical applications, a market involving prognostic and predictive biomarkers is growing rapidly. This is an important space as it represents the segregation of biomarkers into classes based on their clinical utility. Biomarkers will be fundamental to the success of targeted therapeutics in the future.

The implementation of personalized medicine in oncology and beyond requires a precise understanding of disease progression as well as molecular targeting of therapies to interrogate molecular lesions. Prognostic and predictive biomarkers have the power to affect these two functions, respectively. Indeed, many putative biomarkers have been postulated in the literature, but few have successfully been utilized in the clinic. If personalized medicine is to expand and scale across therapeutic classes, biomarkers must proliferate and find clinical utility.

For the rest of the story, click here.

Yan Zhang, Ph.D., and Joyce Peng, Ph.D.

Wednesday, October 08, 2014

Figure 1. Method of sequencing samples from a JAK2-negative myeloproliferative neoplasm patient

As one of the most prevalent causes of death across the globe, the burden of cancer is still sharply increasing, predominantly due to the aging population. As such, the current focus of many researchers is on how to accurately diagnose and treat various cancer types. However, human cancers usually carry several different genomic variations, such as copy number variations and point mutations, which essentially lead to tumor heterogeneity. These tumors therefore display different cellular morphology, gene expression, metabolism, motility, proliferation, and metastatic potential. This phenomenon occurs both within individual tumors and between different tumors in the body.

This inherent variation of cancer cells causes significant issues in the development of targeted therapies. Drug development has previously focused on the genomic differences between complex mixtures of cells, employing techniques that may obscure the heterogeneity of single cells, leading to the development of less efficient treatments.

For the rest of the story, click here.

Caroline Meade and Natasha F. Bonhomme

Wednesday, October 08, 2014

Experts have suggested that in the next decade large-scale sequencing for all healthy babies at birth is plausible. [Source: © Miroslav Beneda - Fotolia.com]

Since 1963, state public health programs have screened newborns for a number of life-altering health conditions. Many of these disorders are rare and genetic, and if caught in the first weeks of life they can be treated or managed to prevent death or a lifetime of disability. Early detection can also help families avoid the lengthy and stressful “diagnostic odyssey” involved in finding out what ails their child (Exe et al.). In 2013, the United States celebrated the 50th anniversary of newborn screening. From scientist Robert Guthrie’s discovery of a test for phenylketonuria to development of state programs that screen every newborn for up to 56 conditions, newborn screening has saved and improved millions of lives. The state-mandated screening gives newborns their best chance for typical development, in large part because of strong national guidelines and efficient state public health systems that have been evolving to support screening for the last 50 years.

As newborn screening success stories gained national notoriety in the early 1960s, scientists quickly discovered diagnostic tests for a host of genetic disorders that could be treated at birth. State public health officials then responded by developing mandatory screening programs with inclusion of increasing numbers of genetic and metabolic conditions. While testing every newborn at birth is a seemingly simple process, organizing the resources required for obtaining samples, analyzing results, diagnosing disorders, and providing follow-up care is a large undertaking for state public health systems.

For the rest of the story, click here.

Alex Philippidis

Wednesday, October 08, 2014

Pharmacovigilance encompasses clinical care optimization, a big data model for efficient targeting of tests and treatments and vigilance for adverse events. [Source: Big Data]

Personalized medicine has long offered more hype than hope. But as genetic knowledge has multiplied in recent years, researchers—and more importantly, computing tools—have begun catching up with all that far-flung data, harnessing it into new databases and systems that offer the best prospects yet for delivering on the promise of precision treatments.

In several papers published this year for which he was corresponding author, Leo Anthony Celi, M.D., M.P.H., clinical research director for MIT’s Laboratory of Computational Physiology, joined David J. Stone, M.D., a visiting professor at University of Virginia and faculty associate at UVA Center for Wireless Health, and others in discussing the challenges that can be addressed with new computing systems, and the key data such systems must capture for clinicians.

In June, Drs. Celi and Stone joined Andrew J. Zimolzak, M.D., a research fellow at Children’s Hospital Boston, in proposing an operational vision for real-time incorporation of external health data through “dynamic clinical data mining” (DCDM), which they envision as driving next-generation electronic medical records (EMRs) as well as “turning medical practice into a data-driven, logical, and optimized system.”

For the rest of the story, click here.

Chris Anderson

Wednesday, October 08, 2014

Source: © marc hericher - Fotolia.com

As the genomic age takes hold, the medical and pharmaceutical industries are just now beginning to scratch the surface of innovation in testing for a wide range of diseases, as well as creating highly targeted therapies based on an individual’s genetic makeup. But as clinicians embrace the great promise of personalized and precision medicine, the explosion of new genetic data is raising often hard-to-answer ethical questions. How should this information be used? How should it be protected? To whom should it be disclosed?

While the government has stepped in with legal protections—most notably the Genetic Information Nondiscrimination Act (GINA)—the scope of these laws don’t have much relevance to clinicians or researchers. In the case of GINA, its protections are largely designed to protect people from being denied health insurance or from discrimination in the workplace based on their genetic information. As a result, policies for the handling of healthcare information are often based on advisory positions of professional societies or formulated on a case-by-case basis.

For the rest of the story, click here.

Wednesday, October 08, 2014

The eleventh issue of Clinical OMICs is available now! Check it out by clicking on the link below.

Clinical OMICs Issue 11

Wednesday, October 08, 2014

Source: © olly - Fotolia.com

CRO med fusion is partnering with genomics technology and services provider GenomOncology to optimize treatment strategies based on the patient's disease state and tumor profile by integrating GenomOncology's technology platform—the GO Clinical Workbench™—and support services with med fusion's soon-to-be expanded solid tumor disease-specific panels. This pairing, the firms say, would offer researchers a comprehensive lab report detailing relevant drug and clinical trial options.

med fusion expects the expansion of its solid tumor menu to come out in the early third quarter of this year with the launch of disease-specific panels including NSCLC (non-small-cell lung cancer) and CRC (colorectal cancer). The expanded menu, the CRO says, is powered in part by next-generation sequencing (NGS) technology that med fusion validated this summer.

GenomOncology says its GO Clinical Workbench can streamline the use of NGS data in conjunction with other analytic modalities, simplify the creation of a summary report, and provide a traceable workflow and rules-based decision support for the clinical interpretation of genomic data. The platform can be configured to each clinical laboratory's specific needs with systems integration (LIMS, EMR, etc.), setting of quality control and annotation parameters, and design of the resultant clinical report.

"Genomics-based precision medicine requires the clinical interpretation of genomic data—streamlined use of next-generation sequencing information in conjunction with other analytic modalities—as well as rules-based decision support," Manuel Glynias, president and CEO of GenomOncology, said in a statement. "The availability of an expert knowledge base like My Cancer Genome, exclusively integrated with the GO Clinical Workbench, provides a clinical report that educates physicians and gives them confidence as they make treatment decisions for patients."

Tuesday, October 07, 2014

Benjamin Darbro, M.D., Ph.D., leader of the winning team.

A project team led by Benjamin Darbro, M.D., Ph.D., director of the Shivanand R. Patil Cytogenetics and Molecular Laboratory at the University of Iowa Hospital and Clinics, has won the inaugural Appistry Pipeline Challenge for developing and executing a pipeline designed to reduce the costs and turnaround times associated with next-generation sequencing (NGS)-based genomics testing. The team has won a complete hardware and software system from Appistry valued at approximately $70,000.

The winning pipeline, Appistry says, will integrate the results of a concurrently run NGS assay and a SNP-containing chromosomal microarray (CMA) to calculate patient specific, genome-wide, NGS-performance metrics (e.g., sensitivity, specificity, positive and negative predictive value) for different types of genetic variations detectable by the CMA platform—performance metrics intended to alleviate the need for confirmatory assays using conventional Sanger sequencing.

Appistry adds that the proposed pipeline will leverage NGS analysis tools provided by the firm—specifically the Genome Analysis Toolkit—along with other tools and a tool developed by the Cytogenetics and Molecular Laboratory called CNV-ROC. The Appistry tools are included as part of Appistry’s Ayrris On Ramp Program for NGS Analysis, a program that includes a developer workstation that can process 200 gigabases per day, Ayrris® software for developing and executing NGS pipelines, and preconfigured analysis tools and starter pipelines. The company is also providing Dr. Darbro a MacBook Air or iPad Air to help facilitate his personal research.

Rich Mazzarella, Ph.D., Appistry CSO and chair of the judging panel for the Pipeline Challenge, said in a statement that the firm’s goal in sponsoring the challenge was to inspire and support innovation that could advance the utility and impact of NGS in clinical labs. “There is enormous promise in the pipeline proposed by Dr. Darbro, and we look forward to assisting in its development over the coming year,” he added.

Friday, October 03, 2014

Sigma-Aldrich says the deal will grow its antibody portfolio and better serve IHC customers. [© Sebastian Kaulitzki - Fotolia.com]

Eleven days after agreeing to be acquired by Merck KGaA for $17 billion, Sigma-Aldrich signaled that it intends to continue growing its presence in diagnostics with clinical applications, saying today it agreed to acquire Cell Marque for an undisclosed price.

Sigma-Aldrich said the deal was intended to strengthen its antibody portfolio and better serve immunohistochemistry (IHC) customers.

The deal—anticipated to close by the end of this year—is subject to regulatory approvals and other customary closing conditions.

Headquartered in Rocklin, CA, Cell Marque employs 90 people and focuses on designing, developing, and manufacturing antibody reagents and kits—including validated, fit-for-purpose antibodies and IHC staining kits aimed at pathologists and clinicians focused on patient management.

“We expect that Cell Marque's strong in vitro diagnostic (IVD) antibody product lines and solid relationships with pathologists and companies that provide automated staining instrumentation will broaden the diagnostic health reach of Sigma-Aldrich," Frank Wicks, Ph.D., president of Sigma-Aldrich's Applied Business Unit, said in a statement.

Sigma-Aldrich said Cell Marque’s will complement its IHC product family, as well as existing workflow solutions for IVD customers. Sigma already manufactures and distributes 230,000 chemicals, biochemicals and other essential products to more than 1.4 million customers globally in research and applied labs as well as in industrial and commercial markets.

Sigma-Aldrich’s offerings would be added to the 60,000 products and solutions now marketed by Merck KGaA’s Merck Millipore unit under their deal, announced Sept. 22. The companies have said the combination will enable Merck Millipore to increase its presence in North America—and perhaps more importantly, add a presence in Asia as R&D and manufacturing continue to expand worldwide.

A key tool for expansion would be continued growth of what is now Sigma-Aldrich’s eCommerce platform, which offers 24-hour delivery in major markets.

Sigma-Aldrich said it expects the Cell Marque acquisition to be “neutral to mildly accretive” to its earnings per share next year. 

Alex Philippidis

Tuesday, September 30, 2014

Source: © inkaone - Fotolia.com

The FDA today issued draft guidance detailing its plans for regulating laboratory-developed tests (LDTs) that it deems as “high-risk” along the lines of Class III medical devices—setting up a showdown with academic medical centers and other developers of the tests, which have opposed efforts at imposing new rules.

In a few days, the agency said, it will launch a 120-day public comment period that will begin with publication of a formal notice of the release of the draft guidances in the Federal Register. Released by the FDA today were two draft guidance documents: Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs); and FDA Notification and Medical Device Reporting for Laboratory Developed Tests (LDTs).

The FDA has historically exercised only enforcement discretion over LDTs designed and used within a single laboratory, and had not sought to regulate their entry to market as is now required for Class III medical devices.

FDA Commissioner Margaret A. Hamburg, M.D., and other agency officials have sought to justify the new rules by saying that today’s LDTs differ from those that were around in 1976 when current rules took effect.

Unlike then, the agency contended in the draft guidances, many of today’s LDTs are much more complex, made with components not legally marketed for clinical use; used beyond local populations; manufactured in high volume; used widely to screen for common diseases rather than rare ones; and used for directing critical treatment decisions such as prediction of drug response.

“There is a wide range of risks associated with the wide variety of LDTs. Thus, FDA believes that a risk-based approach to regulatory oversight of LDTs is appropriate and necessary to protect patient safety,” the FDA stated in its Framework draft guidance.

LDT developers maintain that the tests are “laboratory testing services” and not medical devices subject to the Food, Drug, and Cosmetic Act (FDCA). At present, labs certified under the Clinical Laboratory Improvement Amendments (CLIA) waiver program may develop and use their own diagnostic tests internally, without FDA oversight.

“Subjecting LDTs to FDA regulation would eliminate the very characteristics which make LDTs and the regulatory framework that presently govern them so vital: flexibility and nimbleness in their ability to respond to unmet needs,” Alan Mertz, president of the American Clinical Laboratory Association, said September 9 in written testimony to the U.S. House of Representatives Energy and Commerce Committee Subcommittee on Health. “FDA regulation of LDTs as medical devices would dramatically slow not only the initial premarket approval of new tests, but also improvements to existing tests, delaying access to new and improved diagnostic testing services for patients and clinicians.”

As detailed in July, the FDA said it plans to begin premarketing approval (PMA) review requirements within 12 months after a final guidance for the highest-risk devices and phase it in over four years for the remaining high-risk devices. The devices would stay on the market during FDA review.

The agency said its focus on “high-risk” devices will begin with LDTs that have the same intended use as a cleared or approved companion diagnostic, followed by LDTs with the same intended use as an FDA-approved Class III medical device, and some LDTs designed to determine the safety or efficacy of blood or blood products.

All other LDTs will be prioritized for review using a public process with expert advisory panels “as appropriate,” the FDA said. The agency promised to provide advanced notice on the timing of enforcement of the new rules to manufacturers whose LDTs fall into high- and moderate- risk categories.

The FDA also said it “intends to” publish priority lists for its review of high-risk LDTs within 24 months of a final guidance—with enforcement for the initial prioritized group beginning “no less than 12 months” after the list is announced—as well as publish a priority list for “moderate-risk” LDTs within four years.

For “moderate risk” LDTs, which would be deemed Class II medical devices, labs would have to begin registration, listing, and adverse-event reporting six months after a final guidance is set. PMA for these LDTs would begin five years after final guidance, and be phased in over four years. FDA said it intends to accredit and use third-party reviewers for premarket submissions “as appropriate.”

The FDA said it will hold a webinar on October 23 at 2:00 p.m. EDT, to address clarification questions on the proposed framework. Details on dialing in and viewing the slide presentation are available here.

LDTs introduced to market on the date of publication of the final guidance, and for six months afterward, will be subject to FDA enforcement discretion as is now the case.

Satish Birudukota

Wednesday, September 24, 2014

The IVD market is segmented into clinical chemistry, immunology, hematology, coagulation, microbiology, molecular diagnostics, and other clinical instruments.

In vitro diagnostics (IVD) are a prominent and fast emerging segment of the global healthcare sector. IVD tests analyze human samples such as blood, urine, or tissue and provide information for making healthcare decisions. Key IVD tests include pregnancy test kits, blood glucose tests, laboratory tests for infectious disease, regular blood tests for cholesterol and hemoglobin content, genetic tests for various genetic diseases, etc.

Interest in companion diagnostics is also growing as providers and patients embrace the idea of selecting the best therapy for a particular patient based on their disease-related gene sequence.

IVDs have potential in prevention and early detection resulting in reduced treatment, enhanced therapy success, higher survival rates, and improved quality of life.

For the rest of the story, click here.

Tri Doan

Wednesday, September 24, 2014

Figure 1. Overview of the bioinformatics steps for NGS sequencing data, with the steps that SureCall software performs boxed in green.

While sequencing entire human genomes is an important achievement of next-generation sequencing (NGS) technology, many clinical research goals can be achieved by sequencing a subset of the genome or genes of interest. Targeted sequencing pools large numbers of individual samples to sequence at the same time. This approach lowers the total cost per sample, reduces turnaround time, and produces a more manageable dataset. However, analyzing NGS data requires computational resources and bioinformatics expertise that are a major bottleneck in terms of cost and time, particularly for investigators who want to manage their own experiments.

Agilent has developed an investigator-tailored NGS data analysis tool, called SureCall, that allows clinical researchers who use targeted sequencing panels for inherited diseases, cancer, and other areas to analyze, visualize, and contextualize NGS data using a single application and without need for coding or special hardware (Figure 1).

For the rest of the story, click here.

Gail Dutton

Wednesday, September 24, 2014

CombiMatrix, a specialist in cytogenomics, offers a microarray platform that is designed to conduct miscarriage analysis (which may include clarification of recurrence risks), prenatal analysis, and pediatric analysis.

CombiMatrix, a CLIA-certified laboratory, is bringing microarray analysis to the underserved problem of recurrent pregnancy loss as well as to prenatal testing. CombiMatrix performs microarray assays that deliver more complete results faster than traditional lab tests.

“Between 50% and 60% of all recurrent miscarriages are caused by a chromosomal abnormality,” Mark McDonough, president and CEO, says. To determine whether a chromosomal abnormality such as triploidy is present, tissue collected from a D&C procedure traditionally is sent to a lab for karyotyping, the standard-of-care genetic test.

“The problem is that it can take up to three weeks to get a result with karyotyping, and this technology returns results only 40% to 50% of the time,” McDonough notes. “Microarray-based cytogenic testing, like CombiSNP™, offers results in one week with 95% yield rates.”

For the rest of the story, click here.

Summer E. Allen, Ph.D.

Wednesday, September 24, 2014

Researchers at Keele University have developed SIFT-MS, or selected ion flow tube mass spectrometry, a real-time technique that measures volatile compounds exhaled by patients. SIFT-MS has been used to detect compounds associated with lung cancer, bacterial and fungal infections, and inflammatory bowel disease.

Clinical applications for mass spectrometry technology have exploded in recent years. Mass spectrometry analysis is often faster, cheaper, and more sensitive than other methods and is thus ideally suited for both diagnostics and therapeutic monitoring.

“Mass spectrometry is finally being accepted by microbiologists as a powerful analytical tool and is currently revolutionizing diagnostics,” says Haroun Shah, Ph.D., head of the proteomics research unit for Public Health England. “I think if you visit the smallest hospital laboratory in the U.K. today, you will find the technique either being used or being considered.”

Dr. Shah helped design the first dedicated linear matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) instrument used for clinical microbiology in 2000. In addition, he co-developed the mass spectrometry methods that are now used by clinical laboratories and biotechnology companies such as Bruker and bioMerieux.

For the rest of the story, click here.

John Russell

Wednesday, September 24, 2014

Using frozen tissue remains the method of choice for characterizing the genome, transcriptome, and proteome. But frozen biospecimens, such as those stored in the freezer-boxed cryovials shown here, are neither foolproof nor economical. Room temperature alternatives, say researchers at the University of California, Los Angeles, may be more sustainable.

Biobanking, already a critical resource for bioresearch and medicine, is becoming even more important. According to a forecast prepared by BCC Research, biobanking will represent a $183 billion worldwide market by 2015. Besides rising in value, biobanking is growing more complicated. Questions of science, ethics, administration, and business viability are all part of biobanking’s dynamic landscape. Multiple stakeholders including government, academia, industry, and patients are shaping the field’s policy and practices.

All this ferment suggests that it is an opportune time to review the state of biobanking and identify emerging trends. Accordingly, many biobanking experts are planning to gather at the sixth annual Leaders in Biobanking Congress. This CHI event is scheduled to take place September 15–17 in Seattle.

The event will cover both the business and the science of biobanking, prompting discussion of myriad topics.

For the rest of the story, click here.

Wednesday, September 24, 2014

The tenth issue of Clinical OMICs is available now! Check it out by clicking on the link below.

Monday, September 22, 2014

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How may far-separated objects quickly come into proximity and directly influence each other? In this universe, wormholes are just the thing, at least on the very largest scales. When space curves upon itself, once-distant locations may intersect, say cosmologists and sci-fi gurus, making the universe a more interesting place—one needn’t take light years to traverse unimaginably vast stretches of emptiness.

The universe known as the genome, too, has stretches of seeming nothingness. Called “gene deserts,” these are regions of noncoding DNA or so-called junk DNA. Though far, far away from protein-coding regions, gene deserts are home to lone, single-letter DNA variations that somehow manage to affect the activity of key genes and thereby influence health and disease.

As in the universe at large, there are curves of a sort—or more accurately loops—that occur in the genomic universe. They can bring seemingly isolated variations close to DNA sequences that are directly involved in protein synthesis and cellular function.

That’s the idea. If scientists could identify specific looping interactions, they could solve long-standing mysteries. For example, they could clarify how is it that most of the 70 or so DNA variants associated with breast cancer occur in noncoding regions of DNA. Several of these variants map to gene deserts, regions of several hundred kb lacking protein-coding genes.

Unfortunately, scientists have had difficulty exploring and taking the measure of genomic loops. They have tried in vain to characterize looping interactions, to say nothing of trying to modify them for therapeutic purposes.

Enter Capture Hi-C, a technology that “fishes” for physical interactions between regulatory elements and their target genes. The technology, developed by researchers at the Institute of Cancer, London, has been used to identify where gene desert DNA was most likely to bind with DNA elsewhere, including with known breast cancer genes.

The details appeared September 22 in the journal Genome Research, in an article entitled, “Unbiased analysis of potential targets of breast cancer susceptibility loci by Capture Hi-C.”

“We used CHi-C to investigate long range interactions at three breast cancer gene deserts mapping to 2q35, 8q24.21, and 9q31.2,” wrote the authors. “We identified interaction peaks between putative regulatory elements (‘bait fragments’) within the captured regions and ‘targets’ that included both protein coding genes and long non-coding (lnc)RNAs, over distances of 6.6 kb to 2.6 Mb.”

After reviewing previous approaches to interaction fishing, which included various chromosome conformation capture (3C) techniques and their refinements (up to 4C and even 5C), the authors described the advantages of their “Hi-C” approach. Instead of searching for matches between bait fragments and targets in “one by one,” “one by all,” or even “many by many” fashion, Hi-C searches “all by all”; that is, it provides genome-wide coverage of all possible interactions.

According to Capture Hi-C’s developers, who were led by Olivia Fletcher, Ph.D., a genetic epidemiologist at the Institute of Cancer Research, the technology is an enhanced Hi-C protocol. It overcomes resolution limitations that bedeviled earlier Hi-C approaches by incorporating a sequence capture step. This innovation, asserted the authors of the Genome Research article, allows “high-resolution analysis of all interactions for which one end of the di-tag (the bait end) maps to a pre-specified genomic region (the capture region) and the location of the other end (the target end) is unrestricted (‘many-by-all’).”

“Target protein-coding genes were IGFBP5, KLF4, NSMCE2, and MYC, and target lncRNAs included DIRC3, PVT1 and CCDC26,” the authors reported. “For one gene desert, we were able to define two SNPs (rs12613955 and rs4442975) that were highly correlated with the published risk variant and that mapped within the bait end of an interaction peak.”

“Our research suggests that some of [the single-letter variations in noncoding DNA] may be raising the risk of breast cancer by physically interacting with genes in distant parts of the genome, in order to turn their activity up or down,” said Dr. Fletcher. “Our study provides important clues about the causes of breast cancer, as well as shining a light on the roles played by gene deserts—fascinating, gene-less regions of DNA, the mystery of which we are only just beginning to understand.”

Kat Arney, Ph.D., science communications manager at Cancer Research UK, said: “It’s becoming increasingly clear that the DNA in-between our genes is full of important control switches that turn genes on and off, yet relatively little is known about this ‘dark matter’ within our genome. Studies like this are vital if we’re to understand how DNA changes—whether within or outside genes—affect cancer risk and tumor growth, and to develop more effective treatments based on that knowledge.”

Friday, September 19, 2014

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Thermo Fisher Scientific completed the listing of its Ion PGM Dx next-generation sequencing (NGS) system with the FDA for clinical use as a class II medical device.

Intended for targeted sequencing of human genomic DNA using peripheral whole-blood samples, the system supports the development and implementation of user-defined NGS diagnostic assays in a clinical laboratory and enables 21 CFR Part 11 compliance, according to Mark Stevenson, president of life science solutions at Thermo Fisher Scientific. The system was validated using a large control panel that contains an extensive number of germline variants that are representative of a range of human conditions, he continued, adding that when it is used for diagnostic assay development, customers may define, validate, lock, and publish protocols in a role-based workflow for implementation into routine use, from library construction to variant calling.

“Next-generation sequencing is rapidly becoming an indispensable tool for clinical laboratories around the world, allowing clinical professionals to simultaneously screen hundreds of genes from patient samples to provide key genetic information and enable patient enrollment within clinical trials,” said Stevenson. “The Ion Torrent platform and accompanying reagents provide a number of unique advantages to clinical customers, enabling accurate and reliable genetic variant analysis from more samples due to low DNA input requirements (10 ng) and faster turnaround times that reduce the time of sample to result.”

Thursday, September 18, 2014

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Researchers at Northwestern Medicine say they have developed the first blood test to diagnose major depression in adults. The assay, which works by measuring the levels of nine RNA blood markers, also predicts who will benefit from cognitive behavioral therapy based on the behavior of some of the markers.

In addition, the test showed the biological effects of cognitive behavioral therapy, the first measurable, blood-based evidence of the therapy's success. The levels of markers changed in patients who had the therapy for 18 weeks and were no longer depressed. 

"Blood transcript levels of nine markers of ADCY3, DGKA, FAM46A, IGSF4A/CADM1, KIAA1539, MARCKS, PSME1, RAPH1, and TLR7, differed significantly between participants with MDD [major depressive disorder] (N=32) and ND [nondepressed] controls (N=32) at baseline (q< 0.05)," wrote the investigators in their study (“Blood transcriptomic biomarkers in adult primary care patients with major depressive disorder undergoing cognitive behavioral therapy”) published in Translational Psychiatry. "Abundance of the DGKA, KIAA1539, and RAPH1 transcripts remained significantly different between subjects with MDD and ND controls even after post-CBT [cognitive behavioral therapy] remission (defined as PHQ-9 <5)."

"This clearly indicates that you can have a blood-based lab test for depression, providing a scientific diagnosis in the same way someone is diagnosed with high blood pressure or high cholesterol," said Eva Redei, Ph.D., who developed the test and is a professor of psychiatry and behavioral sciences at the Northwestern University Feinberg School of Medicine. "This test brings mental health diagnosis into the 21st century and offers the first personalized medicine approach to people suffering from depression."

Dr. Redei, who is co-lead author of the study, previously developed a blood test that diagnosed depression in adolescents. Most of the markers she identified in the adult depression panel are different from those in depressed adolescents.

The current method of diagnosing depression is subjective and based on nonspecific symptoms such as poor mood, fatigue, and change in appetite, all of which can apply to a large number of mental or physical problems. A diagnosis also relies on the patient's ability to report his symptoms and the physician's ability to interpret them. But depressed patients frequently underreport or inadequately describe their symptoms.

"Mental health has been where medicine was 100 years ago when physicians diagnosed illnesses or disorders based on symptoms," said co-lead author David Mohr, Ph.D., a professor of preventive medicine and director of the Center for Behavioral Intervention Technologies at Feinberg. "This study brings us much closer to having laboratory tests that can be used in diagnosis and treatment selection."

The new blood test will allow physicians for the first time to use lab tests to determine what treatments will be most useful for individual patients.

Major depressive disorder affects 6.7 percent of the U.S. adult population in a year, a number that is rising. There is a two- to 40-month delay in diagnosis, and the longer the delay, the more difficult it is to treat depression. An estimated 12.5 percent of patients in primary care have major depression but only about half of those cases are diagnosed. A biologically based test has the potential to provide a more timely and accurate diagnosis.

Caroline Meade and Natasha F. Bonhomme

Friday, September 12, 2014

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September is newborn screening awareness month. Since 1963, state public health programs have screened newborns for a number of life-altering health conditions. Many of these disorders are rare and genetic, and if caught in the first weeks of life they can be treated or managed to prevent death or a lifetime of disability. Early detection can also help families avoid the lengthy and stressful “diagnostic odyssey” involved in finding out what ails their child (Exe et al.). In 2013, the United States celebrated the 50th anniversary of newborn screening. From scientist Robert Guthrie's discovery of a test for phenylketonuria to development of state programs that screen every newborn for up to 56 conditions, newborn screening has saved and improved millions of lives. State-mandated screening gives newborns their best chance for typical development, in large part because of strong national guidelines and efficient state public health systems that have been evolving to support screening for the last 50 years.

As newborn screening success stories gained national notoriety in the early 1960s, scientists quickly discovered diagnostic tests for a host of genetic disorders that could be treated at birth. State public health officials then responded by developing mandatory screening programs with inclusion of increasing numbers of genetic and metabolic conditions. While testing every newborn at birth is a seemingly simple process, organizing the resources required for obtaining samples, analyzing results, diagnosing disorders, and providing follow-up care is a large undertaking for state public health systems.


To see the rest of this Genetic Testing and Molecular Biomarkers article click here.

Wednesday, September 10, 2014

The ninth issue of Clinical OMICs is available now! Check it out by clicking on the link below.

Clinical OMICs Issue 9

Shelly Gunn, M.D., Ph.D.

Wednesday, September 10, 2014

Single-gene testing just isn't adequate anymore, especially with the growing number of targeted therapies. Yet many physicians turn to large gene panels only as a last resort. [© khz—iStock]

There are huge benefits to genomic tumor assessment, both for better treatment now, and later, if first-line treatments fail. But I don’t think many cancer patients—and even some physicians—fully understand how important tumor sequencing can be to successful cancer treatment. Yet.

This is not surprising. Outside of a few tests for breast cancer, we really didn’t have the tools to do this sequencing even just five years ago. The first major breakthrough that I saw in clinical practice was for metastatic melanoma, a very rare clinical scenario where the incidence is maybe 10,000 cases a year. Suddenly in August 2011, there was a machine I could put in my lab, and in one day obtain results of a molecular test that had a tremendous impact on treating the patient, according to whether the tumor was BRAF positive or BRAF negative.

From that time on, there has been an increasing number of solid tumors where we can test for a genetic biomarker that indicates a specifically targeted treatment, such as the FDA-approved testing for EGFR in non-small-cell lung cancer and KRAS in colorectal cancer.

Single gene testing just isn’t adequate anymore, especially with the growing numbers of targeted therapies, both currently FDA-approved and in the pipeline. If a lung tumor isn’t being driven by EGFR, then you immediately want to know whether ALK is involved, and if not ALK then what about ROS, MET, PIK3CA, and etc. We need to be looking at multiple genes during our diagnostic testing, not just a few select biomarkers.

For the rest of the story, click here.

Jeffrey N. Gibbs

Wednesday, September 10, 2014

With the issuance of this new framework, the debate over FDA regulation of LDTs is now going to be held in full public view. [© Alexander Raths - Fotolia.com]

In 1992, the Food and Drug Administration (FDA) first stated that it had authority to regulate laboratory-developed tests. On July 31, FDA took its biggest step toward invoking this asserted authority by unveiling its “Framework for Regulatory Oversight of Laboratory-Developed Tests (LDTs).”

In the framework, FDA explains that while it had traditionally exercised enforcement discretion and not regulated LDTs, due to changes in the role and type of LDTs, the agency now intends to regulate LDTs as devices. The agency plans to do this in stages, phased in over a lengthy period of time.

For the rest of the story, click here.

Robin Munro

Wednesday, September 10, 2014

To make better use of genomics data, researchers need to make sure that they are gathering and sharing good quality clinical data as well. [© millaf – Fotolia.com]

It was inspiring to listen to Howard J. Jacob, Ph.D., professor of physiology and human and molecular genetics at Medical College of Wisconsin, speaking a few years back about successfully treating a young boy with an extreme form of inflammatory bowel disease using genome sequencing. It just shows that with the right time, the right data analytics, and expertisze there can be success in bringing genomics to the bedside.

So what needs to happen in genomic medicine to make this exceptional case become more common place? Now, almost four years later, the ambition and vision is there but major challenges still lie ahead.

For the rest of the story, click here.

Chris Anderson

Wednesday, September 10, 2014

According to Combimatrix, noninvasive screens play an important role in prenatal care, but should only be considered a first step.

Prenatal screening for Down syndrome first became available for expectant mothers with the advent, in the late 1960s, of a diagnostic test employing amniocentesis and fetal karyotyping. At the time, only one risk factor was considered—the age of the mother.

In the ensuing years, discoveries showing the correlation between over- and under-expression of specific biomarkers in the mother’s blood, such as alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), estriol, and inhibin A, led to new prenatal screening tests that could indicate the likelihood of not only Down syndrome but other potential birth defects.

While these tests are still widely used and continue to serve a valuable function in helping physicians screen high-risk patients for potential abnormalities, these screening tools also have a relatively high incidence of false positives and false negatives. Women with a normal pregnancy are often referred for unnecessary invasive procedures such as amniocentesis or chorionic villus sampling, both of which carry a risk of miscarriage.

For the rest of the story, click here.


Wednesday, September 10, 2014

University of Illinois researchers developed a cradle and app for the iPhone to make a handheld biosensor that uses the phone's own camera and processing power. [Brian T. Cunningham]

If you had to pick the most compelling mHealth, or mobile health, application, you might well pick mDiagnostics—the ability to perform laboratory work outside the laboratory. mDiagnostics promises to bring on-the-spot testing to poor and remote areas where conventional tools such as microscopes, cytometers, and colorimeters are unavailable.

Mobile, off-the-grid diagnostic tools are best compact. But, beyond that, choices abound. mDiagnostic tools could be sleek, self-contained, standalone devices. Or they could be modular. For example, an mDiagnostic tool could consist of an add-on device plugged into a general-purpose platform, the smartphone.

For the rest of the story, click here.

Monday, September 08, 2014

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Rockland Immunochemicals received a $224,473 SBIR grant from the NIH's National Heart Lung and Blood Institute to develop an antibody-based point-of-care device that can diagnose sickle cell disease. Rockland says it secured the award by demonstrating the technology's ability to develop and produce life science tools for basic and clinical research focused on functional genomics and drug discovery markets.

The firm argues that there are currently no simple screening tests that can differentiate patients with the sickle cell trait (HbAS) from sickle cell disease conditions (HbSS, HbSC and HbS β-thalassemias), but its new antibody technology could help overcome these barriers.

"We will create novel hemoglobin isoform-specific antibodies and configure a lateral flow point-of-care assay," said Rockland’s CSO Carl Ascoli, Ph.D. “As a result of this project, the antibody-based lateral flow point-of-care device will allow rapid and inexpensive diagnosis of sickle cell disease in infants and young children in industrialized and low-income and low-resource settings.”

Rockland recently announced it is expanding, having moved from Gilbertsville, PA, to a 60,000-square-foot facility within the Limerick Airport Business Center in Limerick, PA. In a recent interview with GEN, Rockland's COO Richard Smith said that the move could allow the firm to double its workforce. Smith added that the new site will also allow the company to double its production of antibodies and related products.

Monday, September 08, 2014

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Four cancer research institutes have joined with Illumina to form a consortium that will recommend standards for applying next-generation sequencing to cancer tumors.

The new Actionable Genome Consortium (AGC) said it aims to help oncologists and pathologists determine the best therapeutic and testing strategies for improving patient outcomes. Joining Illumina as founding members of the consortium are Dana-Farber Cancer Institute, Fred Hutchinson Cancer Research Center, MD Anderson Cancer Center, and Memorial Sloan Kettering Cancer Center (MSK).

ACG has articulated its core purpose as creating a comprehensive description of genomic alterations that define individual patients' tumors, or “cancer actionable genome.” To that end, AGC said it has developed and will publish recommendations for:

  • Best practices for biopsy, sample storage and transport, and extraction;
  • Technical performance standards for DNA sequencing;
  • Standards for variant calling, annotation and interpretation;
  • Guidelines for the format and content of clinical reports.

"Widely available, standardized genomic testing of tumors can be the means by which precision oncology and therefore precision medicine begins to live up to its promise," Rick Klausner, M.D., former director of the National Cancer Institute and now Illumina’s SVP & CMO, said in a statement.

Illumina’s co-founding of ACG comes as the sequencing giant looks to grow its business with clinical practices, reflecting the migration of genomic technologies into clinical settings and its ongoing effort to broaden its customer base beyond NIH-funded customers in academia and government.

Illumina and its partners in ACG intend to standardize actionability standards that now vary from provider to provider, complicating efforts to clinically interpret genomic tests. Most patients lack access to multidisciplinary Tumor Boards along the lines of those at major cancer centers which define what constitutes an actionable event in a tumor.

ACG’s recommendations are expected to facilitate development of in vitro diagnostics, additional information to support regulatory oversight of genomic testing for cancer, and reimbursement for new diagnostics.

The consortium also said it plans to carry out research that will leverage the scientific, clinical and technical capabilities of its member institutions for new collaborative, cross-institutional projects to address “grand” challenges in molecular oncology.

"Patients will be more likely to receive the proper targeted course of therapy from the outset when the community oncologist is aware of standard molecular testing procedures and how to interpret these test results," added Charles Sawyers, M.D., chair of the Human Oncology and Pathogenesis Program at MSK and a Howard Hughes Medical Institute Investigator.

Friday, September 05, 2014

Laboratory Corporation of America® Holdings (LabCorp) launched a new business, Enlighten Health Genomics, that builds on the diagnostic potential of next-generation sequencing (NGS) technology. The company said it aims to make genetic profiles a routine part of clinical decisions.

Enlighten Health Genomics combines LabCorp’s infrastructure and capabilities with a team of accomplished geneticists to offer diagnostic capabilities, NGS analysis and interpretation, and informed genetic counseling.

Later this year, Enlighten Health Genomics said it will introduce ExomeReveal, a whole exome sequencing testing service. ExomeReveal can provide genome-wide interpretation for children with serious childhood genetic diseases as well as additional diagnostic information for patients of any age.

“We believe that patients with serious genetic conditions require a thorough interpretation of their genome,” said David Goldstein, genetics professor at Duke University, who will chair Enlighten Health Genomics’ scientific advisory board. “Our goal is to offer innovative and affordable diagnostic solutions to broad patient populations, making genomics a routine part of clinical decisions.”

“Enlighten Health Genomics is an important part of LabCorp’s strategy to capitalize on our unique assets, create new sources of revenue from our core capabilities and meaningfully differentiate us from competitors,” said David P. King, chairman and CEO at LabCorp. “The launch of this business is another tangible step in the development of Enlighten Health, our initiative to create innovative tools and capabilities to enhance patient care.”

Friday, September 05, 2014

Veracyte is planning to launch Allegro's lead lung cancer test in the second half of 2015. [Elnur - Fotolia.com]

Molecular cytology diagnostics firm Veracyte is acquiring Massachusetts-based company Allegro Diagnostics for $21 million—$7.8 million in cash, $13.2 million in Veracyte common stock. Allegro's primary focus is on developing diagnostic tests for lung cancer, and Veracyte plans to launch Allegro's lead lung cancer test in the second half of 2015.

Allegro say its lung cancer test can help physicians determine which patients with lung nodules who have had a nondiagnostic bronchoscopy result are at low risk for cancer and thus do not need invasive procedures. The gene expression test uses a "field of injury" genomic technology platform that allows for the testing of cytology samples obtained through bronchoscopy rather than surgery. The technology can, according to the firm, detect molecular changes that occur throughout the respiratory airways in response to smoking and that are correlated with disease. 

Veracyte's president and CEO Bonnie H. Anderson said in a statement that this acquisition will allow the firm to enter the pulmonology market. "Allegro is a natural fit for us and we believe this move further establishes our leadership in molecular cytology, using genomics to resolve diagnostic ambiguity preoperatively and thus spare patients from unnecessary invasive procedures and reduce associated healthcare costs," she added.

Enal Razvi, Ph.D., and Gary M. Oosta, Ph.D.

Thursday, September 04, 2014

Over 12,000 publications in the POC space from 110 countries were analyzed for this report. [© Anetta - Fotolia.com]

Our goal for this analysis was to understand the landscape of point-of-care (POC) diagnostics, and we believe that an excellent methodology to apply is to analyze the en bloc set of publications in this space.


  • The POC diagnostics field is a global growing space.
  • We have characterized the landscape via a bottom-up analysis of the entire publications ensemble.
  • Specific technologies such as segments of PCR are growing rapidly in this field—testifying to the central role nucleic acid analytes are occupying in POC.
  • There is small overlap with molecular diagnostics, suggesting that the POC field is an independent self-standing entity with significant growth potential.

Click here to download the PDF report.

Wednesday, August 27, 2014

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The National Institutes of Health has issued a final NIH Genomic Data Sharing (GDS) policy to promote data sharing as a way to speed the translation of data into knowledge, products, and procedures that improve health while protecting the privacy of research participants. The final policy was posted in the Federal Register August 26, 2014, and published in the NIH Guide for Grants and Contracts August 27, 2014.

Starting with funding applications submitted for a January 25, 2015, receipt date, the policy will apply to all NIH-funded large-scale human and nonhuman projects that generate genomic data, including research conducted with the support of NIH grants and contracts and within the NIH Intramural Research Program.

A report on genomic data sharing through the NIH database for Genotypes and Phenotypes (dbGaP) appears in the August 27, 2014, advance online issue of Nature Genetics.

"Everyone is eager to see the incredible deluge of molecular discoveries about disease translated into prevention, diagnostics, and therapeutics for patients," said Kathy Hudson, Ph.D., NIH deputy director for science, outreach, and policy. "The collective knowledge achieved through data sharing benefits researchers and patients alike, but it must be done carefully. The GDS policy outlines the responsibilities of investigators and institutions that are using the data and also encourages researchers to get consent from participants for future unspecified use of their genomic data."

Along with statistics about the use of dbGaP data, the Nature Genetics report outlines the challenges facing the field, such as the increased volume and complexity of genomic data.

"Advances in DNA sequencing technologies have enabled NIH to conduct and fund research that generates ever-greater volumes of GWAS [genome wide association studies] and other types of genomic data," noted Eric Green, M.D., Ph.D., NHGRI director, report co-author and a co-chair of the trans-NIH committee that developed the GDS policy. "Access to these data through dbGaP and according to the data management practices laid out in the policy allows researchers to accelerate research by combining and comparing large and information-rich datasets."

A key tenet of the GDS policy is the expectation that researchers obtain the informed consent of study participants for the potential future use of their de-identified data for research and for broad sharing. NIH also has similar expectations for studies that involve the use of de-identified cell lines or clinical specimens.

The two-tiered system for providing access to human data is based on data sensitivity and privacy concerns developed under the GWAS policy will continue. For controlled-access data, investigators will be expected to use data only for the approved research, protect data confidentiality (including not sharing the data with unauthorized people), and acknowledge data-submitting investigators in presentations and publications.

NIH officials say they expect any institution submitting data to certify that the data were collected in a legal and ethically appropriate manner and that personal identifiers, such as name or address, have been removed. The NIH GDS policy also expects investigators and their institutions to provide basic plans for following the GDS policy as part of funding proposals and applications.

The NIH GDS governance structure, described at http://gds.nih.gov/04po2.html, will be responsible for oversight of the GDS policy, including policy needs and issues related to data submission and access. The NIH advises investigators seeking funding to contact relevant extramural program directors or an NIH institute or center Genomic Program Administrator (GPA) as early as possible to discuss data sharing expectations and timelines that would apply to their proposed studies. For a list of GPAs, visit http://gds.nih.gov/04po2_2GPA.html.

Thursday, August 21, 2014

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Illumina formed collaborative partnerships with AstraZeneca, Janssen Biotech, and Sanofi to develop a universal next-generation sequencing (NGS)-based oncology test system. It will be used for clinical trials of targeted cancer therapies with a goal of developing and commercializing a multi-gene panel for therapeutic selection, resulting in a more comprehensive tool for precision medicine.

Illumina is working with its partners to develop assays that detect and measure multiple variants simultaneously to support its partners’ clinical trials, with the objectives of securing regulatory agency approvals and test commercialization. In parallel, Illumina officials say the company also is working with key thought leaders to set standards for NGS-based assays in routine clinical oncology practice, as well as to define regulatory frameworks to enable this new testing paradigm. Together, Illumina and its strategic partners aim to transition from single-analyte companion diagnostics to panel-based assays that select for companion therapeutics.

“The transition to patient-centered companion therapeutics marks a new era for oncology, and we are pleased to see pharmaceutical companies working with Illumina on a universal platform to bring life-saving treatments through their development pipelines,” said Ellen V. Sigal, Ph.D., chair and founder of Friends of Cancer Research. “This is the type of collaboration that will make real progress for patients.”

To date 125 known cancer genes have been discovered—71 tumor suppressors and 54 oncogenes—that drive tumor growth through 12 cellular signaling pathways. While today the number of available targeted therapies is limited, an estimated 800 oncology drugs are in development, many of which are designed to target specific mutations. With the emergence of new targeted therapies, there is growing need for new companion diagnostic tests.

“Building on our experience with the MiSeqDx, the only FDA-cleared NGS platform, as well as the additional regulatory expertise we gained with the acquisition of Myraqa, Illumina is developing the universal test system to support our partners’ oncology drug pipelines,” noted Rick Klausner, M.D., Illumina’s chief medical officer.

Emil Salazar

Wednesday, August 13, 2014

There’s reason to be both optimistic and pessimistic about the United States IVD market, depending on what sectors one wishes to focus on.  Despite persistent challenges to the U.S. in vitro diagnostics (IVD) market, advanced testing segments can lead a bounce-back delivering growth to test innovators—suppliers and labs alike. Chief among recent disappointments in U.S. IVD market performance has been the disruption of histology and molecular markets, previous mainstays of high revenue growth. Recovery in the U.S. IVD market will depend in large part on the contributions of histology and molecular diagnostic testing segments, which are projected to grow by an average of 7.5% per year through 2018. Market expansion for these advanced diagnostics segments will be a result of test introduction and the stabilization of coverage and reimbursement decisions and procedures on the part of payers.

For the rest of the story, click here.

Alex Philippidis

Wednesday, August 13, 2014

The point-of-care testing market can expect significant growth, but cost and compliance challenges still exist. [© Photographee.eu - Fotolia.com]

Point-of-care testing (POCT) is among the fastest-growing areas of laboratory medicine, driven by clinicians’ increased need for technologies that are faster, cheaper, and provide more robust, clinically useful results than ever—a need fueled more recently by the ongoing restructuring of U.S. healthcare through the Affordable Care Act (ACA).

The POCT market is projected to grow to $27.5 billion by 2018 based on a compound annual growth rate of 9.3% since 2013 (MarketsandMarkets), which would peg the current market size at a little over $16 billion. Glucose tests remain the majority of the POCT market—53.7% in 2013 (Reportlinker.com)—but have fallen from 70% in 2011 (RnR Market Research), reflecting expanded use of POCT.

POCT is broad enough to take in the processing lab’s traditional molecular diagnostics increasingly seen in hospitals, home pregnancy or glucose tests, and “rapid diagnostic tests” or RDTs. “Rapid” can range from seconds to hours while patients wait, as long as it’s within a clinical encounter that allows for quick decision-making by the clinician.

For the rest of the story, click here.

Patricia Fitzpatrick Dimond, Ph.D.

Wednesday, August 13, 2014

The growth of genomic medicine has cast a spotlight on the need for higher-resolution technologies for chromosomal analysis. [© fotohunter/iStock]

Detection and analysis of structural variability within chromosomes have become an integral part of genomic medicine. Because genomic instability and chromosomal abnormalities characterize cancer as well as many developmental diseases, understanding these structural aberrations can provide insight into disease etiology, treatment options, and prognosis.

According to physicians, current cytogenetic tests for developmental diseases tests, including G-banded chromosome analysis and fluorescence in situ hybridization (FISH), provide useful information for both clinicians and families, allowing identification of potential medical interventions for the patients. This information, they say, also enables accurate recurrence-risk counseling and helps families plan for the expected natural history of the disease. 

For the rest of the story, click here.

Muin J. Khoury, M.D., Ph.D., and Scott Bowen

Wednesday, August 13, 2014

Each year millions of babies are routinely screened for certain genetic, endocrine, and metabolic disorders, often using a point-of-care test at the bedside. [© millaf – Fotolia.com]

Thirteen years after the completion of the Human Genome Project, an increasing number of genomic applications, including next-generation sequencing (NGS), are poised for clinical use. Fulfilling the promise of genomics to improve health in the real world requires a public health perspective.

As genomics reaches the bedside, a public health “post bedside” research agenda will be able to assess the contribution of genomics and other new markers to health and disease in the larger social and environmental context, evaluate promising genomic technologies for their potential to improve health and healthcare, design appropriate strategies for integrating genomics into clinical and public health practice and ensuring access, and continuously measure population health impact of these new technologies. 

For the rest of the story, click here.

Kate Marusina, Ph.D.

Wednesday, August 13, 2014

Exome sequencing has promise in oncology testing, particularly in the monitoring of disease progression and the prediction of therapeutics responses. To realize this promise, researchers are developing and validating assays of ever-wider scope. [© Zmeel /iStock]

Next-generation sequencing (NGS) not only continues to make steady advances in the molecular diagnosis of cancers, it also seems to fit perfectly with our current knowledge of the oncogenome. In particular, by making it possible to screen the entire coding sequence of cancer-related genes, NGS overcomes a key problem—cancer predisposition cannot be monitored by just a few hotspot mutations.

The sensitivity, speed, and potentially decreased cost per sample make NGS a highly attractive technology. In fact, NGS may soon consolidate many other platforms. While some NGS applications, such as whole-genome sequencing, will probably have to wait several years before they spread and enter routine clinical use, other NGS applications are ready now.

One NGS application that shows immediate promise for clinical oncology testing is exome sequencing. “We hope that in the near future, sequencing of the cancer exome will soon provide oncologists with information they need to identify and utilize treatment options based on the patient’s genomic profile,” says Helen Fernandes, Ph.D., associate professor of pathology and laboratory medicine, Weill Cornell Medical College. Dr. Fernandes, however, adds that NGS will become established in the clinic only after certain challenges are addressed.

For the rest of the story, click here.

Wednesday, August 13, 2014

The eighth issue of Clinical OMICs is available now! Check it out by clicking on the link below.

Clinical OMICs Issue 8

Alex Philippidis

Wednesday, August 13, 2014

Cologuard is designed to analyze DNA alterations and blood in the stool to detect the presence of colon cancer and precancers. [Exact Sciences]

Exact Sciences has won FDA approval for the first noninvasive DNA screening test for colorectal cancer—the first stool-based diagnostic designed to indicate the presence of abnormal growths in red blood cells and DNA mutations, and the first test to be approved under a joint parallel review pilot program by the agency and the Centers for Medicare and Medicaid Services (CMS).

Cologuard® is designed to analyze both stool DNA and blood biomarkers, and is intended for at-home use by adults 50 years old and older. The test has been proven to find 92% of cancers and 69% of the most advanced precancerous polyps in average risk patients, according to Exact Sciences.

Upon FDA approval, Exact Sciences also received a proposed coverage memorandum from CMS under the pilot program, designed to help reduce the time between FDA approval and Medicare coverage by as many as six months. A final National Coverage Determination is expected to be posted in October or November of this year, following a public comment period.

Priced at $599, Cologuard is designed to detect biomarkers from cancer DNA that is shed from the colon as part of the digestive process and blood released in the stool. Through their physician, patients order a Cologuard kit mailed directly to their home. Patients then collect a stool sample via the Cologuard Collection Kit, then send the kit back to the Exact Sciences lab for testing through a pre–paid mailer.

The stool sample is analyzed in an automated system to yield a single test result—positive or negative for the presence of precancerous polyps or cancer. Results from the Cologuard test are turned around in about two weeks, with patients learning their results directly from their physician. Patients with positive test results are advised to undergo a diagnostic colonoscopy.

Cologuard does not require medication or dietary restrictions, or bowel preparation prior to taking the test.

“The test is designed for high accuracy, ease of patient use, and wide accessibility. We hope that it will make a difference and save many lives,” David Ahlquist, M.D., a Mayo Clinic gastroenterologist and co-inventor of the test, said in a statement.

Exact Sciences licenses the Cologuard technology from Mayo Clinic. Under that licensing agreement, Mayo and Dr. Ahlquist share in equity and royalties. Revenue received by Mayo Clinic is used to support its not–for–profit mission in patient care, education and research, the company said.

FDA said its approval of Cologuard does not change current practice guidelines for colorectal cancer screening. Stool DNA testing has yet to be recommended as a screening method for colorectal cancer by the U.S. Preventive Services Task Force (USPSTF). The task force still recommends that adults age 50 to 75, at average risk for colon cancer, be screened using fecal occult blood testing, sigmoidoscopy, or colonoscopy.

According to FDA, Cologuard’s safety and effectiveness were established through the Phase III DeeP–C Study, in which 10,023 subjects were screened. The clinical trial compared the performance of Cologuard to the commonly-used non-invasive fecal immunochemical test (FIT). Cologuard detected 92% of colorectal cancers and 42% of advanced adenomas in the study population, compared with 74% and 24%, respectively, through FIT screening. However, Cologuard gave an accurate negative screening for colorectal cancer or advanced adenomas less often -- 87% of study subjects, versus 95% via FIT.

Results from DeeP–C were published in April in the New England Journal of Medicine.

“Cologuard addresses a critical need for a more convenient screening option for patients to aid in prevention and early detection,” stated Kevin Conroy, the president, CEO and chairman of Exact Sciences. “Exact Sciences is committed to making Cologuard available and accessible to patients and looks forward to advancing cancer detection in other gastrointestinal cancers.”

CMS has proposed coverage for the Cologuard test once every three years for Medicare beneficiaries who are 50 to 85 years old; at average risk of developing colorectal cancer; and show no signs or symptoms of colorectal disease including but not limited to lower gastrointestinal pain, blood in stool, positive guaiac fecal occult blood test or fecal immunochemical test.

Exact Sciences said it plans to make Cologuard available in select countries in Europe pending CE Mark.

Kevin Mayer

Friday, August 08, 2014

A genomic analysis of tumors from 12 tissues of origin reveals a new classification system. It consists of 11 subtypes that appear to reflect the cell type of origin. [Zhong Chen, NIH/NIDCD]

Advancing the work of The Cancer Genome Atlas (TCGA), a large team of researchers from multiple institutions performed a comprehensive analysis of molecular data from thousands of patients representing 12 different types of cancer. The analysis pointed to an alternative system for classifying cancer. Instead of defining cancers according to their tissues of origin, the new system considers molecular subtypes.

When the new system is used, as many as 1 in 10 cancers may be reclassified. In these instances, reclassification may be anything but academic. It may, for example, suggest that cancers from a particular tissue may comprise cancers of different subtypes, each with a different prognosis, each vulnerable, possibly, to different therapies.

A new classification system for cancer could also affect drug development or the recruitment of patients into clinical trials.

The new system was presented August 7 in the journal Cell, in an article entitled “Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin.” This article described how tumors were characterized using six different platforms—mostly genomic platforms such as DNA and RNA sequencing, plus a protein expression analysis.

These platforms generated findings that converged on the same set of 11 molecular subtypes, giving the researchers confidence that the subtypes were valid, as well as suggesting that different kinds of data could be used to classify a particular tumor. Of these 11 subtypes, five were nearly identical to their tissue-of-origin counterparts. Several distinct cancer types, however, were found to converge into common subtypes. For example, lung squamous, head and neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes.

A striking example of the genetic differences within a single tissue type is breast cancer. The breast, a highly complex organ with multiple types of cells, gives rise to multiple types of breast cancer: luminal A; luminal B; HER2-enriched; and basal-like, which was previously known. In this analysis, the basal-like breast cancers looked more like ovarian cancer and cancers of a squamous-cell type origin, a type of cell that composes the lower-layer of a tissue, rather than other cancers that arise in the breast.

Study participants—which included researchers from the University of California, Santa Cruz, Buck Institute for Age Research, University of North Carolina Health Care, and University of California, San Francisco—relied on a method they called cluster-of-cluster assignments (COCA). The COCA subtypes, the researchers noted, could reflect tumors arising from distinct cell types.

“In this new taxonomy, cancers of nonepithelial origin (e.g., neural, muscle, connective tissue) appear most different from epithelial tumors based on virtually all molecular platforms,” wrote the researchers in Cell. “The next most marked difference is apparent between epithelial cancers arising from basal layer-like cells (C2-squamous-like and C4-BRCA/basal) and those with secretory functions (C1-LUAD-enriched and C3-BRCA/Luminal). Molecular commonalities within a COCA subtype suggest common oncogenic pathways.”

“We think the subtypes reflect primarily the cell of origin. Another factor is the nature of the genomic lesion, and third is the microenvironment of the cell and how surrounding cells influence it,” said Josh Stuart, Ph.D., one of the Cell study’s authors and a professor of biomolecular engineering at UC Santa Cruz. “We are disentangling the signals from these different factors so we can gauge each one for its prognostic power.”

Enal Razvi, Ph.D., Gary Oosta, Ph.D.

Tuesday, August 05, 2014

The CVD space is an attractive segment wherein POC diagnostics finds significant utility. [© Alexander Raths - Fotolia.com]

The focus of this GEN Market & Tech Analysis report is to present some of our recent industry tracking of the point-of-care diagnostics (POCD) space.


  • We present the POC diagnostics space with emphasis upon cardiovascular disease (CVD) in this report.
  • The growth of the POC space is exponential and its impact on CVD cannot be ignored.
  • CVD is an optimal therapeutic area for POC diagnostics and in this report we present the reasons for this trend, and the associated biomarkers that are being deployed in POC tests.
  • The expanding POC space and its impact on many other therapeutic spaces is the driver for the market forecast, which predicts >30% growth of POC over the coming years.

Click here to download the PDF report.

Tuesday, August 05, 2014

Source: © fotoliaxrender - Fotolia.com

Scientists from McGill University and the Génome Québec Innovation Centre say they have achieved a technical advance that could result in speedier diagnosis of cancer and various prenatal conditions. Their discovery, which is described online (“Convex lens-induced nanoscale templating”) in the Proceedings of the National Academy of Sciences (PNAS), lies in a new tool developed by Sabrina Leslie, Ph.D., and Walter Reisner, Ph.D., of McGill's physics department and their collaborator, Rob Sladek, Ph.D., of the Génome Québec Innovation Centre.

According to the team, it allows researchers to load long strands of DNA into a tunable nanoscale imaging chamber from above in ways that maintain their structural identity and under conditions that are similar to those found in the human body.

"To overcome the challenges faced by classical nanofluidic technology, we have developed a new approach for introducing tunable nanoscale confinement to trap and align DNA molecules for optical analysis," wrote the investigators. "Our confinement-based imaging technology combines nanotemplated substrates with a single-molecule imaging technique called convex lens-induced confinement (CLIC)."

CLIC will permit researchers to rapidly map large genomes while at the same time clearly identifying specific gene sequences from single cells with single-molecule resolution, a process that is critical to diagnosing diseases like cancer, explained Dr. Leslie. The CLIC tool can sit on top of a standard inverted fluorescence microscope used in a university lab. Existing tools used for genomic analysis rely on side-loading DNA under pressure into nanochannels in the imaging chamber, a practice that breaks the DNA molecules into small pieces, making it a challenge to reconstruct the genome, continued Dr. Leslie.

"It's like squeezing many soft spaghetti noodles into long narrow tubes without breaking them," she said while describing what it is like to use CLIC. "Once these long strands of DNA are gently squeezed down into nanochannels from a nanoscale bath above, they become effectively rigid which means that we can map positions along uniformly stretched strands of DNA, while holding them still. This means diagnostics can be performed quickly, one cell at a time, which is critical for diagnosing many prenatal conditions and the onset of cancer."

"Current practices of genomic analysis typically require tens of thousands of cells worth of genomic material to obtain the information we need, but this new approach works with single cells," added Dr. Sladek. "CLIC will allow researchers to avoid having to spend time stitching together maps of entire genomes as we do under current techniques, and promises to make genomic analysis a much simpler and more efficient process."

Alex Philippidis

Friday, August 01, 2014

Source: ©.shock—Fotolia.com

The FDA said Thursday it intends to regulate laboratory-developed tests (LDTs) that it deems as “high-risk” along the lines of Class III medical devices, positioning itself against academic medical centers and other developers of the tests, which have opposed efforts at imposing new rules.

The agency formally told Congress it will issue within “at least” 60 days a formal draft guidance laying out a detailed, risk-based framework for approving such LDTs [See "FDA’s LDT 'Anticipated Details'" below]. FDA sought to soften the blow for LDT developers by urging them to offer feedback on the draft guidance, and saying it would phase in regulations over several years.

While FDA has long reviewed diagnostic tests, the agency has historically exercised only enforcement discretion over LDTs designed and used within a single laboratory, and had not sought to regulate their entry to market as is now required for Class III medical devices.

LDT developers hold to the agency’s traditional view that the tests are “laboratory testing services” and not medical devices subject to the Food, Drug, and Cosmetic Act (FDCA). At present, labs certified under the Clinical Laboratory Improvement Amendments (CLIA) waiver program may develop and use their own diagnostic tests internally, without FDA oversight.

Answering a GEN question during a briefing for reporters, Jeffrey Shuren, M.D., J.D., director of the FDA’s Center for Devices and Radiological Health (CDRH), said the planned LDT guidance is an effort to reconcile the interests of nonprofit academic medical labs with those of for-profit diagnostic developers.

“Our intent here is to put in place the right balance,” Dr. Shuren said, noting that academic labs can continue using an LDT without obtaining a premarketing approval (PMA) unless another entity has won FDA approval for that test.

“That’s our attempt to try to balance continuing those incentives—for example, the academic labs saying they want to be able to meet the needs of their patients when something [an approved test] is not there—but at the same time, also have the incentives for the conventional medical device diagnostic industry to also develop tests and facilitate innovation in both spaces,” Dr. Shuren said. “That also includes the development of companion diagnostics, which are absolutely critical if we’re going to advance personalized medicine in the U.S.”

FDA also issued a final guidance addressing development, review and approval or clearance of companion diagnostics (CDx). The final guidance—issued three years after FDA’s draft CDx guidance—encourages companies to identify the need for CDx during the earliest stages of drug development, and plan for simultaneous development of a drug and its companion test.

Dr. Shuren said FDA and the Centers for Medicare and Medicaid Services, which oversees CLIA, have long viewed LDTs as medical devices since the tests have entailed chemical reads, instruments and systems used to diagnose, cure, mitigate, treat, or prevent disease. “Labs have actually sent us submissions on their tests. We don’t regulate services, and even those labs acknowledge it, because they send us traditional kinds of tests for our review, asking us for our approval.”

During the briefing, FDA Commissioner Margaret A. Hamburg, M.D., cited “faulty or unproven” LDTs leading to over- or undertreatment for disorders that included heart disease, cancer, and autism. In April, the CDC expressed “serious concerns” about the potential for misdiagnosis due to false positive results from a Lyme disease LDT that used a culture method to identify Borrelia burgdorferi. CDC recommended that the diagnosis of Lyme should be left to FDA-approved tests.

“Just as drugs need to be safe and effective for treating diseases, medical devices used to help diagnose disease and direct therapy also need to be safe and effective,” Dr. Hamburg said. “Without premarket review by the agency, neither patients, nor their healthcare providers, or the FDA itself can be assured that these tests are accurate and reliable.”

FDA acted two weeks after lab directors from 23 academic medical centers urged the U.S. Office of Management and Budget not to release an earlier draft guidance submitted to OMB. “FDA regulation of laboratory developed tests would stifle the medical innovation occurring in academic medical centers today, and interfere with our ability to care for patients,” the lab directors wrote to Brian Deese, OMB’s acting director, on July 16.

Edward R. Ashwood, M.D., president and CEO of ARUP Laboratories and professor of pathology at the University of Utah School of Medicine, led the group in arguing that new regulations would add to the cost and time spent developing new tests while stifling innovative new tests that could deliver on the long-ballyhooed promise of personalized medicine.

However, NIH Director Francis S. Collins, M.D., Ph.D., said FDA’s planned LDT guidance would advance individualized treatment: “This is good news for all who are working to turn the dream of personalized medicine into a reality.”

The lab directors sent their letter two weeks after Sen. Edward J. Markey (D-CA) and four other Democratic senators urged OMB to release the earlier draft guidance. Joining Sen. Markey were Sens. Richard Blumenthal (D-CT), Sherrod Brown (D-OH), Dick Durbin (D-IL), and Elizabeth Warren (D-MA).

FDA’s LDT "Anticipated Details"
In a letter to the Senate Committee on Health, Education, Labor and Pensions and the House Committee on Energy and Commerce, FDA said it plans to begin premarketing approval (PMA) review requirements within 12 months after a final guidance for the highest risk devices and phase it in over four years for the remaining high-risk devices. The devices would stay on the market during FDA review.

The agency said its focus on “high-risk” devices will begin with LDTs with the same intended use as a cleared or approved companion diagnostic, followed by LDTs with the same intended use as an FDA-approved Class III medical device; and some LDTs designed to determine the safety or efficacy of blood or blood products.

FDA said it “intends to” publish priority lists for its review of high-risk LDTs within 24 months of a final guidance, and “moderate-risk” LDTs within four years.

Labs would have to begin registration, listing and adverse-event reporting for “moderate risk” LDTs, which would be deemed Class II medical devices, six months after a final guidance is set. PMA for these LDTs would begin five years after final guidance, and be phased in over four years.

Friday, July 25, 2014

Source: © ktsdesign

Qiagen has acquired an exclusive global license from the University of Tokyo for the biomarker SF3B1. The company said it sees potential for developing companion diagnostics to guide myelodysplastic syndromes (MDS) treatment with new anticancer compounds under development that target the SF3B1 gene.

Mutations of this gene, which Qiagen said is a significant component of the spliceosome machinery, indicate a more favorable disease progression for patients than the wild-type gene, so testing for these gene variants could potentially provide important guidance for treatment.

Qiagen licensed the SF3B1 biomarker in an ongoing expansion of its oncohematology offering for clinical research and diagnostics. Three additional spliceosome biomarkers implicated in various blood cancers and targeting variants in the U2AF35 (U2AF1), ZRSR2, and SFRS2 genes are also part of the license agreement. They are included in Qiagen’s GeneRead DNAseq Leukemia V2 gene panel for next-generation sequencing (NGS), which has been launched earlier this month together with 13 other new cancer gene panels that are compatible with any NGS sequencer and customizable to include other genes or gene regions of clinical or biological interest.

“Building on a broad portfolio of molecular diagnostics for blood cancers, Qiagen continues to partner with clinical researchers at pharmaceutical companies and academic centers, to extend the benefits of personalized healthcare,” said Vincent Fert, Qiagen’s personalized healthcare program leader. “Because several Pharma companies are developing potential anti-cancer drugs targeting the SF3B1 gene, this biomarker also holds potential for codevelopment as a companion diagnostic.”

In May, the company partnered with Eli Lilly to codevelop universal and modular assay panels that can simultaneously analyze DNA and RNA biomarkers targeting multiple cellular pathways involved in common types of cancer and associated with several therapies Lilly is currently developing.

Thursday, July 24, 2014

Source: © drizzd - Fotolia.com

Cypher Genomics and Illumina have made a pact to co-promote Illumina's sequencing technology, the NextBio platform for data analytics and storage, and Cypher's Coral™ biomarker discovery service to pharmaceutical companies. The firms, through Illumina's sales team, will be promoting the products and service together as part of a solution that, they say, can facilitate development of genomic-based biomarkers from whole-genome sequence data for clinical trials and precision medicine.

Cypher says its technology can reduce the signal-to-noise in genomic information to help researchers find important biomarkers in sample sizes of the sort frequently used in early-stage drug development. It also claims that its genomic analysis platform can provide highly accurate genome annotations to enable biomarker discovery studies with sample sizes in the hundreds, which the firm believes would aid many researchers working on Phase II trials.

Nick Naclerio, svp, corporate development and general manager, Enterprise Informatics of Illumina, said in a statement that Coral complements Illumina's whole-genome sequencing and NextBio platform nicely. "We look forward to working with Cypher Genomics to provide our mutual customers with the sequencing, data interpretation, and data mining they require for biomarker discovery with whole-genome data," he added.

Illumina has had a very good year so far: Just yesterday, the firm announced record second-quarter financial results, including a revenue of $448 million, an increase of 29% compared to $346 million in 2013's second quarter. Commenting on the results, Illumina's CEO Jay Flatley said, "With the most extensive sequencing portfolio available, we remain extremely well-positioned to develop and address the large and untapped market opportunities ahead of us."

Alex Philippidis

Wednesday, July 23, 2014

Source: © Igor Mojzes - Fotolia.com

Fulfilling the promise of personalized medicine will require more patient education, greater access to treatments, and new commitments by insurers to pay for the new drugs, an umbrella group that represents more than 200 academic, industry, patient, provider, and payer communities said today.

The Personalized Medicine Coalition (PMC) cited a survey it commissioned that showed only 38% of respondents had ever heard of “personalized medicine”—the targeting of new drugs to patients most likely to benefit from them, using diagnostics to identify biomarkers.

PMC and other proponents say personalized medicine has the potential to revolutionize disease treatment and contain spiraling healthcare costs. Only 11% of those surveyed said their doctor had discussed or recommended personalized medicine to them.

Amy M. Miller, Ph.D., evp of PMC, told GEN the coalition thinks one reason for the lack of patient awareness was the dearth of personalized medicine products and services until lately. That number has climbed, according to PMC, from 13 a decade ago to 113.

“Personalized medicine leads the way in cancer, but there are fewer examples in chronic disease conditions, and I think that’s the other reason why awareness is low,” Dr. Miller said.

A key role in raising patient awareness of personalized medicine, she added, will be played by providers: “They have a very large role to play in raising awareness with the general population about what personalized medicine is and how it can impact healthcare and improve quality.”

During a panel discussion of survey results at the National Press Club in Washington, D.C., Dr. Miller joined three experts in agreeing that advancing personalized medicine will require professionals to agree on a term of art—all agreed on personalized medicine—and to publicize successful treatments.

“If an expectant mother would be able to say that a genetic test might be able to identify if her fetus is going to be healthy, that’s important,” said Raju Kucherlapati, Ph.D., Paul C. Cabot Professor in the Harvard Medical School Department of Genetics. “For a patient who is suffering from cancer to be able to hear us say, ‘What is the drug or combination of therapies that is most likely to be effective in your case?’ That’s what resonates with people.”

Dr. Kucherlapati was joined on the panel by Randy Burkholder, vp of policy at Pharmaceutical Research and Manufacturers of America (PhRMA); Donna Cryer, J.D., president and CEO of the Global Liver Institute; and Mark Richards, svp and management supervisor with survey conductor KRC Research. They joined Dr. Miller in unveiling findings from the survey, which questioned 1,024 American adults by landline and mobile phone from March 5–16. The margin of error for the total sample was plus or minus 3 percentage points.

According to the survey, almost two-thirds of respondents (65%) reacted mostly positively to a description of personalized medicine, with 37% saying they were very likely to undergo a diagnostic test toward an individualized treatment plan. Another 40% said they were “somewhat’ likely.

However, more than two-thirds of patients pinpointed two overlapping concerns with personalized medicine—that their insurers won’t cover it (69%) or they cannot afford it (67%).

PMC is calling for insurers to fund new personalized treatments. That is near-certain to be resisted by the payers, which have balked at reimbursing providers for the sky-high price of new drugs designed for subpopulations and want drug developers to shoulder more of the cost. Drugmakers also balk at paying more, contending that it would slow down the development of new medicines, and that they need to recoup R&D expenses.

Yet the developers face growing political pressure to contain drug costs. Since March, four Democrats in the Republican-majority U.S. House of Representatives have criticized Gilead Sciences for charging $84,000 per 12-week treatment for the chronic Hepatitis C virus treatment Sovaldi™ (sofosbuvir). One of the four, U.S. Rep. Henry A. Waxman (D-CA) is set to join two advocacy groups Wednesday in calling for reduced Medicare drug costs.

Waxman is ranking member of the House Committee on Energy and Commerce, which on Wednesday will host a “21st Century Cures” roundtable talk on personalized medicine whose speakers will include PMC President Edward Abrahams, Ph.D.

“We need to have a conversation about how to streamline development and approvals for personalized medicine products and services”—both drugs and diagnostics, Dr. Miller said. “We need to talk about how to streamline FDA processes for co-developed drug-diagnostic combination products, how to get those to market more quickly. And when we talk about a standalone diagnostic, we need to talk about what kind of evidence needs to be presented to payers, so they feel comfortable and confident in covering those innovative tests.”

She said payers can be persuaded to support new tests that show clear benefits, citing recent decisions by insurers to reimburse providers for noninvasive prenatal tests for trisomy disorders such as Down syndrome.

“We see this as an opportunity to discuss what personalized medicine means holistically,” Dr. Miller said. 

Monday, July 21, 2014

Source: © Elena Kovaleva - Fotolia.com

Berry Genomics chose Illumina's next-generation sequencing technology as the platform on which Berry will aim to secure Chinese Food and Drug Administration (CFDA) regulatory approval for clinical applications. The goal is to expand access to NGS-based tests in China.

The companies say have co-developed an NGS system to provide a cost-effective, easy-to-use assay for noninvasive prenatal testing. A working version of the new assay and instrument system has been validated in clinical settings in China, and is in late-stage review under the CFDA's medical device registration process.

The new system integrates Berry Genomics' Bambni™ assay, which includes a library preparation kit, analysis software, and a sequencing instrument based on Illumina's NextSeq™ 500 sequencing system.

"There are two million high-risk and advanced maternal age pregnancies a year in China, which is about three times the size of the U.S. market. We need to ensure we are addressing women's needs by offering a safe and proven technology. As the first and only company with a U.S. FDA cleared next-generation sequencing instrument, Illumina is an ideal collaboration partner given their experience," said Daixing Zhou, CEO of Berry Genomics.

"This agreement is an example of our commitment to working with clinical companies in China and worldwide who want to develop and commercialize in vitro diagnostics based on next-generation sequencing," added Greg Heath, svp, IVD development at Illumina.

Thursday, July 17, 2014

Source: © FotolEdhar - Fotolia.com

Beckman Coulter said today it agreed to acquire the clinical microbiology business of Siemens Healthcare Diagnostics for an undisclosed price.

Siemens’ clinical microbiology business specializes in microbial identification and antibiotic sensitivity testing (ID/AST). The business operates with an installed base of over 6,000 instruments globally, and is part of Siemens’ diagnostics division, which finished last year with $5.332 billion (€3.942 billion) in revenue.

Today’s announcement by Beckman Coulter—an indirect, wholly owned subsidiary of Danaher—ends months of speculation over the future of Siemens’ clinical microbiology business. In March, BioMerieux CEO Jean-Luc Belingard told Reuters his company would look at acquiring the business from Siemens, which the wire service said had been offering through bankers “around $500 million” for its clinical microbiology operations, citing unnamed sources.

Siemens’ microbiology product line includes the MicroScan® Instruments and MicroScan panels/consumables, along with data management solutions. The MicroScan systems are designed to deliver high accuracy and superior detection of emerging resistance.

“The clinical microbiology business will be an excellent complement to Beckman Coulter's Diagnostics business with a strong reputation and market position,” Beckman Coulter Diagnostics President Arnd Kaldowski said in a statement. “Adding its ID/AST solutions to our existing products and services will create an opportunity to enhance our offerings to laboratory customers and improve patient care.”

Kaldowski added that the acquisition will expand Beckman Coulter’s product portfolio with differentiated analytical systems that elevate the company’s clinical capabilities for customers, while driving continued growth.

Siemens’ deal with Beckman Coulter is expected to close in the first quarter of 2015, subject to regulatory approvals and other customary closing conditions.

Earlier this month, Bloomberg reported that Siemens was looking to refocus on its energy and industrial businesses, citing unnamed sources as saying the German conglomerate was also looking to sell off its hospital database and IT business.

Adding credence to that talk was Siemens restructuring its operations in May, in part by giving greater operational independence to its healthcare businesses. CEO Joe Kaeser at the time insisted that the action was not intended to signal a sell-off but to increase their ability to address a changing market.

However, Morningstar analyst Debbie Wang speculated to the Boston Business Journal that Siemens may still wish to grow in diagnostics, saying the company was one of two most likely suitors for Alere. The comment followed a shakeup of Alere’s management that led an outspoken shareholder to say publicly that the point-of-care diagnostics developer had received unsolicited offers from potential strategic acquirers in the past year. 

Alex Philippidis

Thursday, July 17, 2014

To increase the chances of being successful, MDx labs should decide on a suitable menu of molecular tests that align with available resources early on. [©.shock—Fotolia.com]

Bringing molecular testing to the clinic is now easier than in past years, thanks to deeper knowledge about the genome and gene variants, increased automation and efficiency, user-friendlier technology, and improved methods to monitor quality.

Incorporating these and other basics into a successful molecular diagnostics (MDx) lab requires clinicians to address opportunities and challenges much as in creating any other lab. In many cases, that means managers must develop business plans that show administrators how their MDx lab intends to succeed clinically and financially. There’s a lot of competition: More than 600 medical laboratories nationwide, plus another 200 independent labs, carry out molecular diagnostics tests.

For the rest of the story, click here.

Alex Philippidis

Thursday, July 17, 2014

Greg Lucier has made his first investment since his days as chairman and CEO of Life Technologies as a member of the investor group behind Edico Genome.

A San Diego startup whose technology promises to enable the clinical use of genomics by radically reducing the cost and time of analyzing next-generation sequencing (NGS) data is attractive enough to have drawn Gregory Lucier among investors that have joined to raise $10 million in Series A financing.

Lucier has made his first investment since his days as chairman and CEO of Life Technologies as a member of the investor group behind Edico Genome, which announced the financing today and said it plans to bring to market its Dynamic Read Analysis for Genomics (DRAGEN) Bio-IT Processor this fall.

The group was led by Qualcomm’s venture investment group Qualcomm Ventures, and included Axon Ventures—as well as Lucier, who will join Edico’s board of directors: “Edico Genome's solution to speed data analysis and lower costs has the potential to have a large impact on many areas of medicine, particularly in oncology and noninvasive personal testing,” Lucier said in a statement.

According to Edico, DRAGEN slashes the time needed to analyze a whole human genome from 24 hours to just 18 minutes, while retaining the accuracy of today’s analysis carried out by clusters of large servers. A single DRAGEN accelerator card can do the work of the 50 servers needed to analyze, for example, the more than 18,000 whole human genomes a year produced by a full Illumina HiSeq X Ten system, at a savings of $6 million over four years. That savings includes reduced compute requirements, lower overhead costs (such as for IT staff, power, and rack space), and reduced data upload costs and data storage costs, since DRAGEN also compresses the raw data for long-term storage.

Introduced in January at the JP Morgan Healthcare Conference, HiSeq X Ten dazzled investors and others by breaking the $1,000-genome sequencing cost barrier—a figure that includes reagents and sample prep, DNA extraction, hardware, and labor. DRAGEN is designed to lower that expense further by drastically cutting hardware costs, which Illumina has estimated at $137, assuming 116 “runs” per year per system, each run sequencing 16 genomes, and four-year depreciation.

“If you look at HiSeq X Ten and you do [analysis] on servers, including storage and everything, all that processing, etc., it’s about $150 per whole-genome sequence. Ours is a fraction of the cost—maybe in the $20–$30 kind of range,” Edico’s CEO, Pieter van Rooyen, Ph.D., told GEN.

Dr. van Rooyen likens Edico’s technology to the smartphones that have supplanted the brick-sized cellphones of a generation ago, which in turn he likens to today’s NGS analysis tools: “They’re where cellphones were in the ‘80s, big and clunky. What we’re doing is aiming to bring sequencing, in terms of the processing of data, out of the ‘80s, at least into the ‘90s, but we have the fundamental technology to bring it all the way into the iPhone of the future, if you will.”

The technology, according to Edico, is the world’s first NGS bioinformatics application-specific integrated circuit (ASIC). Embedded on a PCIe form factor card, DRAGEN will be sold with accompanying software as a platform-as-a-service or Paas platform for integration into sequencers and NGS bioinformatics servers. DRAGEN uses a processor with algorithms for mapping, alignment, sorting, and variant calling.

Instead of analyzing the torrent of sequencing data in software through a general purpose processor, Dr. van Rooyen said, DRAGEN uses its own dedicated processor that runs the tailored algorithms: “We have architecture on our chip that facilitates the movement of the data and the processing of the data in an optimal way. That’s why we can do it on one chip as opposed to an all-server form of Intel CPUs.”

Dr. van Rooyen is one of three founders of Edico. The others are Robert McMillen, Ph.D., vp of engineering, and Michael Reuhle, director of system architecture. DRAGEN will be launched commercially during the American Society of Human Genetics’ 64th Annual Meeting, set for October 18–22 in San Diego.

“We believe genomics is the future of healthcare, and our technology is really enabling the uptake of genomics,” Dr. van Rooyen said. “Hopefully in five or 10 years, everybody’s going to have a personalized sequencer, and our technology is just a first step on the processing side in realizing that kind of future. It’s a fundamental technology that can be extended to the future and allow the processing of the data in a very simple, dedicated chip.”

He said a huge part of Edico’s success to date has been its ability to benefit from EvoNexus™, the business incubator of CommNexus™, a nonprofit high-tech trade organization in San Diego. Edico is one of 28 startups housed by EvoNexus, through which Edico connected with its investors, including Qualcomm as well as Lucier, whose Life Tech was acquired by Thermo Fisher Scientific for about $13.6 billion, plus assumption of $1.5 billion in net debt, in a deal completed February 3.

The incubator has a relationship with Qualcomm through the Qualcomm Labs initiative, which facilitated an earlier seed investment in Edico by Qualcomm Ventures—and led to the financing from Qualcomm Ventures.

Richard Mazzarella, Ph.D.

Wednesday, July 16, 2014

The first printout of the human genome as displayed at the Wellcome collection, London [Russ London—Wikicommons]

The Human Genome Project provided a path for determining the genetic basis of many inherited diseases and neoplasms. So far, various efforts from both research institutions and private companies have yielded myriad single gene and disease panel tests for both cancer and various Mendelian diseases, which have proven quite useful in diagnosing and treating specific conditions. The scope of single gene tests is limited, making them less effective at identifying a patient’s underlying disease state and appropriate cancer drug regimens. Large cancer panels containing all the actionable genes do better at elucidating this type of information. The maturation of next-generation sequencing (NGS) technology, though, has made whole-exome and whole-genome studies viable options, especially if they can be used to assemble a mineable knowledge base that could yield a more comprehensive understanding of disease.

For the rest of the story, click here.

Gary E. Marchant and Rachel A. Lindor

Wednesday, July 16, 2014

Medical malpractice lawsuits are a double-edged sword. On the one hand, liability can compensate injured patients and push providers to implement the most up-to-date technologies and practices. On the other, the threat of liability can result in wasteful defensive medicine and drive up insurance premiums.

New medical technologies such as personalized medicine trigger both edges of the liability sword. On the positive side, the threat of liability may compel providers to more quickly uptake useful genetic tests and data, but on the negative new liability risks and uncertainties created by personalized medicine may incentivize premature or inappropriate utilization of genetic tests and drive up insurance premiums.

For the rest of the story, click here.


Patricia Fitzpatrick Dimond, Ph.D.

Wednesday, July 16, 2014

Determination of an individual’s risk for severe arrhythmias before a life-threatening event occurs remains a significant medical challenge. [© kmiragaya - Fotolia.com]

Advances in molecular diagnostics, physicians say, have the potential to improve identification of cardiac diseases and further understanding of mechanisms responsible for their pathogenesis and phenotypic expression. These tests may also predict the need for specific treatment, or help avoid unnecessary therapies and invasive diagnostic procedures.

And, scientists add, while genomic research in cardiovascular disease (CVD) has progressed rapidly over the last few years, “groundbreaking observations” have not yet been accompanied by clinically applicable tools for risk prediction, diagnosis, or therapeutic interventions.

For the rest of the story, click here.

Dan Koboldt

Wednesday, July 16, 2014

Comprehensive molecular profiles of the most common cancer types are now available. [NHGRI]

As you have probably noticed, there’s been a major shift in the focus of next-gen sequencing over the past couple of years. First it was all about new genomes, new techniques, and discovery. Now it’s all about translation. We are entering a new era in next-gen sequencing, one in which NGS technologies will not only be used for discovery, but will be integrated into clinical care.

A review in the latest issue of Human Molecular Genetics discusses NGS-enabled cancer genomics from the clinician’s point of view. In it, the authors highlight recent findings from large-scale cancer genomics efforts—such as the Cancer Genome Atlas—and offer their perspectives on the significant challenge facing us: translating the knowledge from such massive “oncogenomic” datasets to the clinic.

For the rest of the story, click here.

Wednesday, July 16, 2014

The seventh issue of Clinical OMICs is available now! Check it out by clicking on the link below.

Clinical OMICs Issue 7

Monday, July 14, 2014

Source: © pearl - Fotolia.com

Stanford University School of Medicine researchers say they have developed an inexpensive, portable, microchip-based test for diagnosing type 1 diabetes that they believe could improve patient care worldwide and help researchers better understand the disease.

Described in a paper (“A plasmonic chip for biomarker discovery and diagnosis of type 1 diabetes”) published in Nature Medicine, the test employs nanotechnology to detect type 1 diabetes outside hospital settings. The handheld microchips distinguish between the two main forms of diabetes mellitus, which are both characterized by high blood-sugar levels but have different causes and treatments.

Until now, making the distinction has required a slow, expensive test available only in sophisticated healthcare settings, according to Brian Feldman, M.D., Ph.D., assistant professor of pediatric endocrinology, the Bechtel Endowed Faculty Scholar in Pediatric Translational Medicine, and the senior author of the paper. The scientists are seeking FDA approval of the device.

“With the new test, not only do we anticipate being able to diagnose diabetes more efficiently and more broadly, we will also understand diabetes better, both the natural history and how new therapies impact the body,” said Dr. Feldman.

Better testing is needed because recent changes in who gets each form of the disease have made it risky to categorize patients based on their age, ethnicity, or weight, as was common in the past, and also because of growing evidence that early, aggressive treatment of type 1 diabetes improves patients' long-term prognoses, continued Dr. Feldman.

Decades ago, type 1 diabetes was diagnosed almost exclusively in children, and type 2 diabetes almost always in middle-aged, overweight adults. The distinction was so sharp that lab confirmation of diabetes type was usually considered unnecessary, and was often avoided because of the old test's expense and difficulty. Now, because of the childhood obesity epidemic, about a quarter of newly diagnosed children have type 2 diabetes. And, for unclear reasons, a growing number of newly diagnosed adults have type 1.

Type 1 diabetes is an autoimmune disease caused by an inappropriate immune-system attack on healthy tissue. As a result, patients' bodies stop making insulin, a hormone that plays a key role in processing sugar. The disease begins when a person's own antibodies attack the insulin-producing cells in the pancreas. The autoantibodies are present in people with type 1 but not those with type 2, which is how tests distinguish between them.

“Delayed diagnosis of T1D [type 1 diabetes] can result in severe illness or death, and rapid diagnosis of T1D is critical for the efficacy of emerging therapies,” wrote the investigators. “However, attempts to apply next-generation platforms have been unsuccessful for detecting diabetes biomarkers. Here we describe the development of a plasmonic gold chip for near-infrared fluorescence–enhanced (NIR-FE) detection of islet cell–targeting autoantibodies. We demonstrate that this platform has high sensitivity and specificity for the diagnosis of T1D and can be used to discover previously unknown biomarkers of T1D.”

In addition to new diabetics, people who are at risk of developing type 1 diabetes, such as patients' close relatives, also may benefit from the test because it will allow doctors to quickly and cheaply track their autoantibody levels before they show symptoms, explained Dr. Feldman, who added that because the test is so inexpensive, it may also allow the first broad screening for diabetes autoantibodies in the population at large.

Monday, July 14, 2014

Source: © London_England - Fotolia.com

Transplant Genomics (TGI) now has an exclusive license to patent rights co-owned by The Scripps Research Institute and Northwestern University that could form the basis for clinical tests to improve management of organ transplant recipients. TGI is planning to use the technology to develop and commercialize tests that use genomic markers of transplant graft status as part of program to detect and respond to early signs of graft injury in patients.

This licensing agreement gives TGI access to intellectual property related to kidney and liver transplant diagnostics including immune status monitoring and optimization. TGI says its first test will be used to monitor kidney transplant recipients, indicating when treatment or biopsy is required based on analysis of a patient’s blood.

Michael Abecassis, M.D., founding director and chief clinical advisor of TGI, said in a statement that the tests could be used to watch patients with good kidney function to aid in immunosuppression decisions. "The test will also find a major and immediate application in circumstances where a sudden elevation in creatinine is noted by the clinician and a biopsy is not possible because of logistical issues," he added.

"The scientific founders of TGI have uniquely combined biomarker discovery with clinical validation and insight to set the stage for high-impact collaborations designed to move the transplant field forward," commented Stanley Rose, Ph.D., president & CEO of Transplant Genomics. Dr. Rose is himself the recipient of a kidney transplant.

Syamala Ariyanchira, Ph.D.

Thursday, July 10, 2014

A recent report estimates the global demand for PCR technologies in 2013 to be around $10.6 billion. [Caleb Foster - Fotolia.com]

The polymerase chain reaction (PCR) has come a long way during the past three decades to become one of the fundamental platforms in life sciences sector. Normally, this is a sufficiently long period for a technology to mature and the market to move to decline phase. However, the PCR industry is witnessing increasing excitement both in terms of innovation and demand. The expiry of key PCR patents is one of the major factors driving this growth allowing more companies to get involved. These new and emerging companies are actively involved in developing new applications and expanding the market to various end-use segments. Even though the technology is considered mature, the demand is still on the rise due to this market expansion. Enthusiasm in the emerging markets is particularly visible and is a major driver of the demand. Overall, these developments are offering improved accessibility to PCR-based diagnostics and other products.

Automation and multiplexing are improving the technology in terms of its ease-of-use and speed making the technology more user-friendly and effective. These critical factors have significant impact in end-use markets. For instance, physicians are adapting to PCR-based screening and disease diagnosis in critical medical diagnostics areas even in emerging countries. Responses from regulatory bodies across the regional markets are also promising, encouraging the utilization of PCR tests in various end-use segments.

Even in this almost “post-patent era” of PCR, the market players are facing significant challenges while treading in the murky waters of PCR patents. Careful analysis to identify patents that are still enforceable is needed, depending upon the markets being considered. The high cost of commercial PCR assays is another challenge, particularly in clinical diagnostics field. Alternate technologies such as NGS are also emerging as threats to the PCR market, since they have the potential to make PCR obsolete in many end-use segments as their cost efficiency improves. The emergence of dPCR could also prove to be a threat to real-time PCR in at least some of the end-use segments. Digital PCR is currently in its initial growth stages, and the application of the technology in various clinical segments is being actively promoted by the technology suppliers.

The recent report published by AcuBiz Consulting titled “The Worldwide Markets of PCR Technologies” estimates the global demand for PCR technologies in 2013 to be around $10.6 billion. The demand grew from 2012 by 6.1% in 2013. The market is expected to grow at a compound annual growth rate (CAGR) of approximately 8% to reach $15.6 billion by 2018. Regionally, the report divides the global market into North America, Europe, Asia Pacific (APAC), and ROW. While North America is expected to show continuous growth trends, growing at a CAGR of 6.1%, the APAC region shows the highest growth potentials. This region is forecasted to grow at a CAGR of 11.2%.

In terms of end-use segments, the largest application segment for PCR products in 2013 was medical diagnostics, as presented in Figure 1. The demand for PCR products for medical diagnostics applications is expected to grow at a CAGR of 8% between 2013 and 2018. The largest subsegment within medical diagnostics is infectious disease diagnostics. There is a rising demand from patients as well as physicians for speedy and accurate diagnosis at affordable costs, which is driving the demand for PCR assays in the medical diagnostics field, even in emerging markets.

Figure 1. Global demand for PCR technologies by end-use segments, by value (USD, billions).

Figure 1. Global demand for PCR technologies by end-use segments, by value (USD, billions).

Detailed patent analysis with respect to various PCR technologies during the past three decades shows growing patenting trends in all the key end-use segments. The patent analysis clearly indicates a rise in PCR application development activities in these segments, as expected after the expiry of key PCR patents. Cancer, infectious diseases, and food safety testing include some of the other major end-use segments where activities related to patenting of PCR diagnostics tools are highly intense. Cancer has been an area of focus of PCR patents since its early years. The intensity of patenting in this area is still high and growing strong as indicated in Table 1, where the number of patents related to key oncology segments during the past decade and the past three years are compared. For instance, leukemia-related PCR patents accounted for almost 25% of the total PCR patents indicating that PCR is a cornerstone of molecular diagnosis in leukemia research.

Table 1. PCR-based diagnostics—patenting trends in selected cancer segments. <sup>a</sup>

Table 1. PCR-based diagnostics—patenting trends in selected cancer segments. a

In general, many different types of cancers became the focus of PCR assay developers during the past decade, and the trend is intensifying as evident from the increasing numbers of patents during the past three years in Table 1. Occasionally, the increasing patenting activities are in correlation with the launch of novel drugs or vaccines indicating a sudden rise of focus on the targeted disease by the healthcare industry. For example, the launch of the Gardasil vaccine in 2006 against HPV and hence as potential prevention for cervical cancer could have influenced the rise in patenting activities related to cervical cancer diagnostics during the past decade, which is still continuing as indicated by the number of hits during the past three years. 

Regulatory landscapes play significant roles in influencing the growth of PCR markets. The emergence of PCR as an important tool in various end-use segments across the globe is in accordance with the increasing approval by regulatory authorities in the regional markets. Key regional markets are analyzed in detail in the report for understanding the regulatory landscapes. The medical diagnostics and food safety testing segments where application of PCR tools are becoming popular, leading to increased attention from regulatory agencies, are particularly analyzed since more regulations can be expected in these fields during the forecast period. The report includes analyses of various guidelines regarding PCR data collection and interpretation in key end-user market segments.  

The PCR market is consolidating as key players are being bought over by bigger diagnostic companies. The acquisition of Life Technologies by Thermo Fisher Scientific in February 2014 is a typical example of this market trend. However, the numbers of new market entrants are increasing. The focus of many of these new companies includes development of new PCR diagnostic products targeting new end-use segments. Some of these companies are based in emerging markets such as India, China, Korea, Southeast Asia, Latin America, and Eastern Europe. While most of these are small and startups, their influence in shaping the demand in their respective domestic markets cannot be ignored.  

Syamala Ariyanchira, Ph.D., (syamala@acubiz.com.co) is a principal consultant at AcuBiz Consulting, a Malaysia-based life sciences consulting firm.

Thursday, July 10, 2014

Source: Andrzej - Fotolia.com

Genetic counseling services provider InformedDNA released today a white paper on genetic testing. Use of these diagnostic tests is growing rapidly, but inappropriate testing has negative consequences for individuals and the U.S. health care system, according to the company.

The paper, titled Genetic Counseling: Connecting Patients to the Power of Genetics and authored by Rebecca Sutphen, M.D., Amber Trivedi, and Kelle Steenblock, delves into the complexity of testing, gaps in physician understanding, issues regarding access, current guidelines, and the role of trained genetics specialists in helping patients maximize the effectiveness of genetic testing, while avoiding unnecessary, wasteful testing.

"Genetic counseling provided by trained specialists can bridge the gap between patients and the appropriate use of genetic testing. It provides an evidence-based solution that allows specialists to ensure the right patient gets the right test," said Dr. Sutphen, president and chief medical officer of InformedDNA. "The results of a genetic test can also have an enormous impact on future health care-related choices. Genetics specialists help patients evaluate their results and make more informed choices based on the best and most current information available."

While genetic testing can provide a life-saving service, it only paints a partial picture of a patient's health risks. To accurately determine a patient's risk-profile, the following steps are taken by genetic specialists:

  • Conduct a complete personal and family history risk assessment.
  • Determine whether a patient is appropriate for genetic testing and, if so, which test is right for them.
  • If a test is ordered, interpret the results in the context of the patient's family history and help them develop a personalized care plan in coordination with their physicians.

However, there are gaps in physician knowledge of genetics and with more than 10,000 genetic tests available, it's not surprising that as many as half of tests are ordered inappropriately. Misuse of genetic testing can carry a number of unintended consequences. In 2010, annual spending on genetic testing eclipsed $5 billion and could reach $25 billion within a decade.

As payers continue to look for ways to reduce costs, consulting with genetic specialists can safeguard insurers against paying for diagnostics that are not medically useful, while also improving quality of care.

"Inappropriate testing can have unintended consequences for patients, even beyond their individual health," noted Steenblock, InformedDNA's senior vp for clinical services. "Genetic counselors help patients navigate these difficult issues."

Wednesday, July 09, 2014

Source: © Alex Tihonov - Fotolia.com

Scientists at the Icahn School of Medicine at Mount Sinai, along with colleagues in the U.K. and Spain, report they discovered that key genetic variants may affect how cancer patients respond to radiation treatments. The research team found that variations in the TANC1 gene are associated with a greater risk for radiation-driven side effects in prostate cancer patients, which include incontinence, impotence, and diarrhea.

The current results are based on a genome-wide association study (“A three-stage genome-wide association study identifies a susceptibility locus for late radiotherapy toxicity at 2q24.1”) published in Nature Genetics.

“Our findings, which were replicated in two additional patient groups, represent a significant step toward developing personalized treatment plans for prostate cancer patients,” said Barry S. Rosenstein, Ph.D., professor, radiation oncology, genetics and genomic sciences, Icahn School of Medicine at Mount Sinai. “Within five years, through the use of a predictive genomic test that will be created using the data obtained in the recent study, it may be possible to optimize treatment for a large number of cancer patients.”

For the study, Dr. Rosenstein and his team obtained blood samples from nearly 400 patients who were receiving radiotherapy treatment for prostate cancer. The blood samples were screened for roughly one million genetic markers, and each patient was monitored for at least two years to track incidents of side effects from the radiation. Data analysis showed which genetic markers were consistently associated with the development of complications following radiotherapy.

“[Our] results, together with the role of TANC1 in regenerating damaged muscle, suggest that the TANC1 locus influences the development of late radiation-induced damage,” wrote the investigators.

“The next step is to validate the results, and see if the same markers predict similar outcomes in patients with other forms of cancer,” explained Dr. Rosenstein. Using the genomic test being developed, treatment plans can be adjusted to minimize adverse effects thereby allowing for an improved quality life for many cancer survivors.

Monday, July 07, 2014

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Sequence-based clinical diagnostics firm and deCODE genetics spinout NextCODE Health is partnering with the Academic Centre on Rare Diseases (ACoRD) at University College Dublin, allowing ACoRD to use NextCODE products in research aimed at learning more about the causes and better ways to diagnose autism and rare diseases.

NextCODE's Clinical Sequence Analyzer™, which the firm says can identify causal mutations in families with different rare disorders, and Sequence Miner and the GOR™ database infrastructure, to be used for mining whole-genome data for sequence variants linked to autism spectrum disorders, are among the technologies to be used.

Sean Ennis, Ph.D., director at ACoRD, UCD School of Medicine and Medical Science, and co-founder of the Irish Autism Genetics Collaboration said in a statement that ACoRD wants to establish a reputation for being a center of excellence in the field of rare genomics. "Sequencing is a powerful means to identify the causes of disease, but it requires the ability to efficiently store and query truly vast amounts of data. NextCODE's system has done this on an unparalleled scale, and can deliver diagnoses on a case-by case basis and enable large-scale discovery efforts," he added.

NextCODE Health was launched with $15 million in venture capital back in October after securing a five-year exclusive license for sequence-based clinical diagnostic applications using technology developed by deCODE genetics. NextCODE says the deCODE system has enabled over 350 publications in gene discovery, diagnostics, and medical applications.

Monday, June 30, 2014

Illumina's HiSeq 2500

Illumina entered three separate deals with three European labs under which they will use Illumina's consumables and the HiSeq 2500 to develop and perform noninvasive prenatal testing (NIPT) in their respective nations. French lab-testing service firm Biomnis will make NIPT available in France, Italian molecular genetics lab Genoma will perform NIPT services in Italy, and the Center for Human Genetics and Laboratory Diagnostics Martinsried (near Munich) will offer NIPT in Germany.

Earlier this year at the JP Morgan 32nd Annual Healthcare Conference, Illumina said it planned to expand its offerings based on the verifi® laboratory-developed NIPT, which the firm picked up upon acquiring noninvasive prenatal testing firm Verinata Health last year. Tristan Orpin, Illumina's svp and general manager of reproductive and genetic health, said in a statement that he feels these three agreements will help establish the firm as a global leader in reproductive and genetic health solutions and a partner for next-generation sequencing-based testing for clinical applications.

Francesco Fiorentino, Ph.D., CEO and director of Genoma Group Laboratories, said that the Italian lab chose to work with Illumina because of its deep sequencing capabilities. "We are continuously trying to improve our service and offerings for patients and healthcare providers, and we believe our physician customers and the expectant families they work with will be thrilled to have access to this important information in an accurate, safe, and efficient manner," he added.

"Backed by whole-genome sequencing, we look forward to making our highly accurate test accessible to physicians and their patients," commented Charles Woler, M.D., Ph.D., CEO of Biomnis Laboratories.

John Sterling

Thursday, June 26, 2014

Source: © kentoh - Fotolia.com

Consider this scenario:

“In five or ten years, you will show up at your doctor’s office, not feeling well, with a thumb drive that contains all your important health-related information, including a copy of your entire genome. Your physician will run the disk through a sophisticated computer and, after studying the results, prescribe a treatment, maybe even a form of genetic engineering or gene therapy, based on the genomic components of your disease, not just your symptoms.”

Fact or Fiction?

“The full-blown version of this five-year scenario is fiction,” says David Smith, Ph.D., professor of laboratory medicine and pathology at the Mayo Clinic. “Now having your genome on a disk in five years will very likely be a reality but being able to fully interpret your genome’s data and make a clinically important decision remains more in the realm of fiction.”

For the rest of the story, click here.

Mitzi Perdue

Thursday, June 26, 2014

Sharon Terry is president and CEO of Genetic Alliance.

The task of finding and recruiting sufficiently large cohorts for studying genetic diseases has up to now been a needle in the haystack problem. This is rapidly changing as Sharon F. Terry, and her colleagues at Genetic Alliance are making possible aggregation of individual health information in ways and on a scale never seen before. In the process, they may play an unprecedented role in speeding up drug discovery while enabling individuals to have more ownership of and participation in their own health.

Terry heads Genetic Alliance, an organization composed not only of more than 1,200 disease-specific health advocacy organizations, but another 8,000 or so university, government, and private sector groups. Having such a large number of organizations working together may soon make possible research that up until now would have been impossible.

For the rest of the story, click here

Alex Philippidis

Thursday, June 26, 2014

Incidental findings occur in clinical, research, and direct-to-consumer contexts. [Photocanal25/iStock Photos]

Recent developments reveal both the beginnings of consensus, and many more unresolved issues, when it comes to “incidental” or unexpected findings uncovered during genome or exome sequencing.

The American College of Medical Genetics and Genomics (ACMG) retreated in April from its controversial recommendation last year that labs should return incidental findings to the doctor ordering the sequencing for discussion with patients regardless of their preference. The suggestion applies to ACMG’s minimum list of 57 genes it recommends be sequenced for mutations involving any of 24 disorders “where early intervention is likely to reduce or prevent serious morbidity or early mortality.”

ACMG argued last year that genes should be sequenced no matter a patient’s age or indication that triggered the sequencing, while patients who refused consent should not be sequenced. After criticism from numerous physicians, other clinicians, and patient advocates, ACMG now recommends that patients should have the choice of opting out of analysis of their medically actionable genes following whole exome or genome sequencing.

For the rest of the story, click here.

Chris Anderson

Thursday, June 26, 2014

Celgene is using NanoString’s nCounter analysis system to support the clinical validation and development of a companion diagnostic for Revlimid, for treatment of Diffuse Large B-Cell Lymphoma.

As recently as ten years ago, just after completion of the Human Genome Project, the concept of a personalized approach to cancer treatment was largely just that—an idea of what could be. And companion diagnostics were limited to predicting patient response to Herceptin for breast cancer and Gleevec for chronic myelogenous leukemia.

But it was the introduction of these therapies along with the nascent field of gene sequencing that began to move the treatment of cancer from a broad-based, one-size-fits-all approach to one that seeks to better understand the unique underlying molecular pathology of each patient’s cancer.

“In the 1990s the pharmaceutical companies argued that because the cancer population is small the only way you could develop a drug and profit from that was by using a broad spectrum chemo approach,” said Richard Ding, CEO of bioTheranostics, a provider of prognostic and diagnostic cancer tests. “Because then you can hit on multiple tumor types and have a broad cluster.

“I think the poster child for changing this was Herceptin. It was able to demonstrate that even though the target population for breast cancer of 50,000 or 60,000 was once considered too narrow, that even with the complexity of making monoclonal antibodies, it showed you can make a business out this.”

For the rest of the story click here.

Thursday, June 26, 2014

The sixth issue of Clinical OMICs is available now! Check it out by clic