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CLINICAL OMICS ISSUE 11 NOW AVAILABLE

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

Clinical OMICs Issue 11
 



News & Perspectives

Perthera, Northwestern University Enter Personalized Cancer Medicine Alliance

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.


New Class of "Good Fats" Protects against Diabetes

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.”


Roche Nabs AbVitro's PETE Technology to Support Clinical NGS

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.


Prognostic vs. Predictive Biomarkers

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.


Single-Cell Approach to Personalized Medicine

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.


Newborn Screening: Adapting to Advancements in Whole-Genome Sequencing

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.


Playing Catch-Up with Data

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.


How Much Genetic Information Is Too Much Information?

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.


med fusion, GenomOncology Team Up to Personalize Cancer Treatments

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."


Appistry Pipeline Challenge Winner Announced

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.


Sigma-Aldrich to Acquire Cell Marque

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. 


FDA Issues Draft Guidance on LDTs

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.


Multifaceted IVD Market Growing Rapidly

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.


Investigator-Completed NGS Data Analysis

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.


Microarray Testing for Unmet Needs

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.


Clinical Mass Spec Attains Critical Mass

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.


Rising Interest in Biobank Deposits

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.


CLINICAL OMICS ISSUE 10 NOW AVAILABLE

Wednesday, September 24, 2014

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

Genomic Wormholes May Be Shortcuts to Breast Cancer

Monday, September 22, 2014

Source: © Picture Partners - Fotolia.com

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.”


Thermo Fisher Lists Its Ion PGM DX System as Class II Clinical Medical Device

Friday, September 19, 2014

Source: © Mopic - Fotolia.com

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.”


First Blood Test Developed for Diagnosing Depressed Adults

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.


Newborn Screening: Adapting to Advancements in Whole-Genome Sequencing

Caroline Meade and Natasha F. Bonhomme

Friday, September 12, 2014

Source: © Francois du Plessis - Fotolia.com

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.


CLINICAL OMICS ISSUE 9 NOW AVAILABLE

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


Why the Controversy? Start Sequencing Tumor Genes at Diagnosis

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.


FDA Announces Intention to Regulate LDTs as Devices

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.


Near or Far? Omics Data Management, Analysis, and Action

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.


Honing Prenatal Screening Tests

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.


Smartphone Based Biosensors—Just What the mDiagnostician Ordered

KEVIN MAYER

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.


Rockland Wins SBIR Grant for Sickle Cell Disease POC Device

Monday, September 08, 2014

Source: © extender_01 - Fotolia.com

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.


Cancer Centers, Illumina Form Group to Set Cancer NGS Standards

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.


LabCorp Launches New Genomics Initiative through Enlighten Health

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.”


Veracyte Picks Up Allegro Diagnostics for $21M

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.


Eye on Point-of-Care Diagnostics

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.

Highlights:

  • 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.


NIH Publishes Finalized Policy on Genomic Data Sharing

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.


Illumina Partners for Development of Universal NGS Oncology System

Thursday, August 21, 2014

Source: © SSilver - Fotolia.com

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.


Elements of Change—How Molecular Diagnostics and Histology Will Deliver Growth to U.S. IVD Market

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.


Point-of-Care Reaches a Crossroads

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.


Cytogenomic Analyses for Genetic Disease Detection and Diagnosis

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.


The Public Health Role in Translating Advances in Genomics

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.


NGS Ready for Clinical Oncology Testing

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.


CLINICAL OMICS ISSUE 8 NOW AVAILABLE

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


FDA Approves First Noninvasive Colorectal Cancer Test

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.


Genome Study Overhauls Cancer Categories, Shifts from Tissues to Molecular Subtypes

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.”


POC Diagnostics in the Cardiovascular Disease Space

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.

Highlights:

  • 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.


Novel Diagnostic Genomic Analysis Technique Developed

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."


FDA to Require Premarketing Approval for "High-Risk" LDTs

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.


Qiagen Adds Cancer Biomarkers to Personalized Healthcare Pipeline

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.


Illumina, Cypher Genomics to Co-Promote Biomarker Discovery Products

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."


Personalized Medicine Proponents Focus on Patients, Insurers

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. 


Berry Genomics and Illumina Partner on NGS System for Chinese Clinics

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.


Beckman Coulter to Acquire Clinical Microbiology Business from Siemens

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. 


Clinical Laboratory, Meet Molecular Diagnostics

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.


Edico Genome Draws Greg Lucier among Investors

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.


The Value of Present and the Promise of Future Sequencing Strategies

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.


Will Liability Drive Personalized Medicine?

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.

 


Molecular Diagnostics in Cardiovascular Disease

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.


The Future of Cancer Genomics

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.


CLINICAL OMICS ISSUE 7 NOW AVAILABLE

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


Diagnosing Type 1 Diabetes with Nanotechnology

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.


Transplant Genomics Picks Up Transplant Dx IP

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.


Expanding End-Use Segments Drive PCR Growth Worldwide

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.


Maximizing the Efficacy of Genetic Testing

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."


Genetic Variant Linked to Radiation-Induced Toxicity in Cancer Therapy

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.


University College Dublin Taps NextCODE to Aid in Autism, Rare Disease Research

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.


Illumina Expands Noninvasive Prenatal Testing in Europe

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.


Integrating Clinical Genomics Data into Standard Medical Practice

John Sterling

Thursday, June 26, 2014

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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.


In Genetic Haystacks, We're All Needles: Sharon Terry and Genetic Alliance

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


Unexpected Findings Anything but “Incidental”

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.


Cancer Treatment Gets Personal

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.


Clinical OMICs Issue 6 Now Available

Thursday, June 26, 2014

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

Clinical OMICs Issue 6


Making the Case for Personalized Medicine

Wednesday, June 25, 2014

Source: © Alexander Raths - Fotolia.com

Personalized medicine is gaining momentum, but it needs yet more impetus to break into the healthcare mainstream, argues a new report. Released on June 25 by the Personalized Medicine Coalition (PMC), the report examines opportunities for the continued development and adoption of personalized medicine as the cost of genetic sequencing declines, the pharmaceutical industry increases its commitment to personalized treatment, and the public policy landscape evolves.

According to the report, personalized medicine is poised to:

  • Shift the emphasis in medicine from reaction to prevention.
  • Direct the selection of optimal therapy and reduce trial-and-error prescribing.
  • Help avoid adverse drug reactions.
  • Increase patient adherence to treatment.
  • Improve quality of life.
  • Reveal additional or alternative uses for medicines and drug candidates.
  • Help control the overall cost of health care.

The report, which is entitled “The Case for Personalized Medicine,” strikes a confident tone, citing progress along scientific, technological, and commercial fronts. Advances include a more than 16,000-fold decrease in sequencing costs over the past 10 years, a 57% increase in products the last three years, and a steadily growing number of drugs with labels that include pharmacogenomic information. In 2006, there were 13 prominent examples of personalized drugs, treatments, and diagnostics on the market. In 2011, there were 72, and today there are 113.

Despite these advances, the report soberly notes that technological changes need to be accompanied by cultural and institutional changes: “Such rapid developments … make it imperative for us to encourage the development and adoption of personalized medicine. It is essential to have appropriate coverage and payment policies, as these will encourage continued investment in new molecular diagnostics. We need regulatory guidelines that adapt to and encourage the coupling of diagnostics and medicines that target genetically defined populations. And professional education must be modernized to prepare the next generation of doctors and other health care professionals for personalized medicine.”

The report, now in its fourth edition, is scheduled to debut later today at The Personalized Medicine and Diagnostics Forum at the 2014 BIO International Convention in San Diego. “BIO is very pleased to co-host [the forum] with the PMC,” said Paul Sheives, director of BIO’s diagnostics and personalized medicine policy. “PMC’s The Case for Personalized Medicine defines the field and contributes to our understanding of how developments in science and technology are creating new opportunities to address unmet patient needs.”

“In a time of unprecedented scientific breakthroughs and technological advancements, personalized health care has the capacity to detect the onset of disease at its earliest stages, pre-empt the progression of disease, and, at the same time, increase the efficiency of the health care system by improving quality, accessibility, and affordability,” said Edward Abrahams, president of the PMC. “We’ve come a long way, but we have a lot to do, especially in education and advocacy.”

The PMC’s report offers these conclusions: “Personalized medicine offers significant short- and long-term benefits, especially for chronic and complex diseases. Payment and reimbursement policies should not discourage interventions that may raise short-term costs but improve clinical/cost value over time. Policies that recognize the principles of personalized medicine will allow physicians to individualize treatment plans for patients through the early diagnosis of disease, target treatments to optimize clinical outcomes, and prevent unnecessary hospitalizations and care, thus reducing long-term costs.

“Innovators are responsible for developing the collective evidence to justify the contention that personalized medicine can improve outcomes while controlling costs. Except in the case of some individual products, to date they have not proven that contention. When they do, our argument will be more compelling.”


Cancer Genetics Buys Gentris for Up to $6.25M

Monday, June 23, 2014

Source: © Robert Mizerek - Fotolia.com

Cancer Genetics (CGI) said today it plans to acquire Gentris, in an up-to-$6.25 million deal that the buyer said will significantly expand its client base beyond oncology diagnostics, through added capabilities in genomic profiling for clinical trials as well as in pharmacogenomics.

“We view this acquisition as part of our long-range strategic plan to deepen our capabilities in developing unique and individualized treatment insights in oncology,” Cancer Genetics CEO Panna Sharma said in a statement. “Gentris will add immediate incremental revenue and, through its established client base and relationships, will give us tremendous access to the biotech and pharmaceutical communities."

CGI said it signed a nonbinding letter of intent to acquire privately held Gentris. The deal is expected to close in the third quarter of this year, subject to a definitive acquisition agreement and related documents, as well as customary closing conditions and government approvals.

Once CGI closes on the Gentris acquisition, and a planned $1.9 million acquisition of BioServe India announced last month, Sharma said, Cancer Genetics will have about 60,000 square feet of lab space for oncology focused patient testing and biopharma trials globally: “This global footprint will allow us to partner with biotech and pharma customers and access innovations through a network of global collaborations and development initiatives.”

Founded in 2001, Gentris provides pharmacogenomics, genotyping, and biorepository services to the pharmaceutical and biotech industries. Gentris partners with pharmaceutical, academic and technology clients to help them effectively integrate pharmacogenomics into their drug development and clinical trial programs, with the goals of delivering safer, more effective drugs to market more quickly.

Publicly traded CGI said it will fully integrate Gentris’ more than 40 employees, including its founder, and Gentris’ facilities. Gentris is headquartered in Morrisville, NC, and last year opened an FDA-compliant satellite laboratory focused on genomic biomarker testing and biorepository services in Shanghai’s Zhangjiang Hi-Tech Park.

As part of the deal, a Gentris founder and board member, Michael P. Murphy, will serve as general manager as CGI integrates the Raleigh facility. Howard McLeod, PharmD, a Gentris board member and director who also serves as medical director at the DeBartolo Family Personalized Medicine Institute at the University of South Florida Moffitt Cancer Center, will join CGI’s Scientific Advisory Board.

CGI agreed to shell out $4.75 million—to consist of $3.25 million cash and $1.5 million in stock—as well as an additional $1.5 million tied to unspecified performance.

"By combining our expertise with Cancer Genetics, we expand the opportunity to service the large, global pharmaceutical companies that already are our customers and also bring together the analysis of somatic and germline genetic changes that drive cancer growth and treatment response," added Tim Gupton, chairman and board member of Gentris. 


VIEW NOW—Clinically Actionable Genomics: From Sequencing to Personalized Medicine

Wednesday, June 18, 2014

Appistry's CSO Richard Mazzarella, Ph.D., and Cancer Genetics' Molecular Diagnostics Director Weiyi Chen, Ph.D., are speakers.

The DxMA webcast "Clinically Actionable Genomics: From Sequencing to Personalized Medicine" sponsored by Clinical OMICs is now available for viewing. This webcast focuses on describing the technologies and strategies—such as genome sequencing, massive amounts of genetic data, bioinformatics, and analytics—that are transforming genomic data into clinically actionable intelligence.

You will learn:

  • How new gene-based tests have transformed diagnosis, prognostication, risk assessment, and treatment of some cancers
  • How informatics companies are developing and delivering reports incorporating tests, sequencing, analysis, and interpretation for physicians
  • What future tests are currently in development

Who should watch:

  • Pathologists
  • Oncologists
  • Cancer drug developers
  • Clinical laboratory scientists

CLICK HERE to view the webcast.


Horizon, LGC Awarded Research Grant for Cancer Diagnostics

Monday, June 16, 2014

Horizon Discovery and LGC have been offered a research grant of £360,224 ($608,000) by the Technology Strategy Board, the U.K.’s innovation agency. The grant is awarded under the board’s collaborative research and development project "Improving Cell and Tissue Analysis for Stratified Medicine" and will fund a joint project run by the company’s Horizon Diagnostics division in partnership with LGC. Horizon will receive more than half of the funding.

The program will establish methods and cross platform datasets to standardize existing liquid biopsy genetic diagnostic tests to determine test sensitivity and to help drive the development of more sensitive systems as well as training and proficiency testing schemes for pathology laboratories.

Horizon will use its gene editing expertise and GENESIS™ platform (comprising rAAV, CRISPR/Cas9, and ZFN technologies) to engineer cell lines carrying cancer genetic markers. These cell lines will be used to generate reference standard material including formalin-fixed paraffin embedded cell blocks and genomic DNA. LGC, which is the U.K.’s designated National Measurement Institute for chemical and bioanalytical measurement, is developing methods using digital PCR for accurate value assignment of reference materials and will test the reference standard material produced by Horizon. LGC is also developing these methods to detect tumor DNA in the bloodstream.

“Horizon is committed to investing in new, innovative areas related to cancer and diagnostics, supporting the increased implementation of stratified and personalized intervention strategies,” said Paul Morrill, Ph.D., senior vice president of Reagent Products at Horizon.

“The combination of Horizon’s reference materials and LGC’s assays—PCR primers and probes—gives the potential for development of kits that clinical laboratories can use with their existing platforms,” said Carole Foy, principal scientist from LGC’s molecular and cell biology department. “These standardization tools will be invaluable in ensuring the accuracy of the results when detecting tumor DNA in the bloodstream.”


Trovagene, Dana Farber to Test Urine-Based Cancer Mutation Tracking

Monday, June 16, 2014

Source: © Alexander Gospodinov - Fotolia.com

Molecular diagnostics firm Trovagene is teaming up with the Dana-Farber Cancer Institute to investigate quantitative urine-based mutation detection—both its utility and the ability to monitor both tumor mutation burden and treatment response over time—in metastatic melanoma patients.

Using urine samples collected from patients suffering from locally advanced or metastatic melanoma known to harbor driver oncogene mutations, a Dana-Farber team led by Jason Luke, M.D., will conduct clinical studies to monitor those mutations in study participants based on urinary cell-free DNA as a specimen.

Dr. Luke said in a statement that, whereas most forms of cancer monitoring are either too invasive or don't provide enough genomic information to reveal how well tumors respond to treatment, a urine-based test has the potential to fix both of those problems. "Based on study data that Trovagene has presented at medical meetings thus far, we are encouraged that urinary cell-free DNA has potential to offer a noninvasive solution for tracking oncogene mutations during and after treatment, and this may help physicians improve patient outcomes," he added.

Back in March, Trovagene also made a partnership with Catholic Health Initiatives Center for Translational Research to determine the effectiveness of Trovagene's urine-based cell-free DNA cancer monitoring diagnostics in clinical practice. The first study under this agreement is expected to start in 2014's second quarter.

Urine-based cancer tests likewise made the news back in February when a team from MIT announced the development of a paper test that the team claimed could reveal within minutes whether a person has cancer.


The Promise of Panomics: Decoding Biological Networks to Identify Pathways Involved in Complex Diseases

Szilard Voros, M.D.

Thursday, June 12, 2014

Cardiovascular computed tomography (CT) permits heart disease patients to be precisely separated using noninvasive imaging techniques. [G3]

Technological advances such as high-throughput sequencing are transforming medicine from symptom-based diagnosis and treatment to personalized medicine as scientists employ novel rapid genomic methodologies to gain a broader comprehension of disease and disease progression. As next-generation sequencing becomes more rapid, researchers are turning toward large-scale pan-omics, the collective use of all omics such as genomics, epigenomics, transcriptomics, proteomics, metabolomics, lipidomics and lipoprotein proteomics, to better understand, identify, and treat complex disease.

Genomics has been a cornerstone in understanding disease, and the sequencing of the human genome has led to the identification of numerous disease biomarkers through genome-wide association studies (GWAS).1 It was the goal of these studies that these biomarkers would serve to predict individual disease risk, enable early detection of disease, help make treatment decisions, and identify new therapeutic targets. In reality, however, only a few have gone on to become established in clinical practice.1,2 For example in human GWAS studies for heart failure at least 35 biomarkers have been identified but only natriuretic peptides have moved into clinical practice, where they are limited primarily for use as a diagnostic tool.2

For the rest of the story click here.


Medically, Proteomics Advances Will Rival the Genetics Advances of the Last Ten Years

Mitzi Perdue

Thursday, June 12, 2014

N. Leigh Anderson

Seventy percent of the decisions made by physicians today are influenced by results of diagnostic tests, according to N. Leigh Anderson, founder of the Plasma Proteome Institute and CEO of SISCAPA Assay Technologies. Imagine the changes that will come about when future diagnostics tests are more accurate, more useful, more economical, and more accessible to healthcare practitioners. For Dr. Anderson, that’s the promise of proteomics, the study of the structure and function of proteins, the principal constituents of the protoplasm of all cells.

In explaining why proteomics is likely to have such a major impact, Dr. Anderson starts with a major difference between the genetic testing common today, and the proteomic testing that is fast coming on the scene. “Most genetic tests are aimed at measuring something that’s constant in a person over his or her entire lifetime. These tests provide information on the probability of something happening, and they can help us understand the basis of various diseases and their potential risks. What’s missing is, a genetic test is not going to tell you what’s happening to you right now.”

For the rest of the story click here.


Counselors Face a Balancing Act as Challenges Loom

Alex Philippidis

Thursday, June 12, 2014

For counselors, making the genome accessible means balancing two roles—working with clinicians to collect the genetic data, while helping patients navigate often-sensitive information about themselves or loved ones. [© Rob - Fotolia.com]

Angelina Jolie’s self-disclosure of the BRCA1 gene mutation that led her to undergo a double mastectomy helped normalize the concept of genetic testing and counseling more than a year ago. Clinical practitioners agree that more patients are aware of genetic testing and counseling because of what has been called the “Angelina effect.”

Yet counselors are still grappling with numerous challenges to their roles that include ever-increasing amounts of data, addressing patient awareness of available services, matching patients with the best tests, and helping ensure that insurance pays for them.

Perhaps the most basic challenge: Genetic counsel for patients is as specific as their genes. And genetic knowledge has only in recent years unfolded to the degree that sound interpretation is even possible.

“The problem is that we’re still on the road to being able to give a comprehensive view of what it is that we can tell somebody in a snapshot just based on their genome,” Elissa Levin, MS, CGC, head of genomics and integrative health innovations at Icahn School of Medicine at Mount Sinai, told Clinical OMICs.

“I really see the genome as a baseline background that we will essentially tap into at multiple different touch points throughout our life cycle. One of the challenges is, how do we do that?” added Levin, who is also assistant professor of genetics and genomic sciences at the Icahn Institute for Genomics and Multiscale Biology at Mount Sinai.

“How do we make the genome accessible across different practices, across different health systems, across different providers who also may not have knowledge about how to interpret genomic information or multivariate information?”

For the rest of the story click here.


Driving Mass Spec-Based Multiplexed Protein Biomarker Tests to the Clinic

Vicki Glaser

Thursday, June 12, 2014

An automated process for SISCAPA targeted protein quantitation utilizes high affinity capture antibodies that are immobilized on magnetic beads.

Clinical proteomics applications rely on the translation of targeted protein quantitation technologies and methods to develop robust assays that can guide diagnostic, prognostic, and therapeutic decision-making. The development of a clinical proteomics-based test begins with the discovery of disease-relevant biomarkers, followed by validation of those biomarkers.

"In common practice, the discovery stage is performed on a MS-based platform for global unbiased sampling of the proteome, while biomarker qualification and clinical implementation generally involve the development of an antibody-based protocol, such as the commonly used enzyme linked ELISA assays," state López et al. in Proteome Science (2012; 10: 35–45). "Although this process is potentially capable of delivering clinically important biomarkers, it is not the most efficient process as the latter is low-throughput, very costly, and time-consuming.”

For the rest of the story click here.


Clinical OMICs Issue 5 Now Available

Thursday, June 12, 2014

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

Clinical OMICs Issue 5


ASHG, JAX Launch Clinical Genetic Education Collaboration

Wednesday, June 11, 2014

From left to right: Director of JAX Genomic Medicine Charles Lee, Ph.D.; JAX president and CEO Edison Liu, M.D.; JAX’ vp for education Thomas Litwin, Ph.D.; and ASHG evp Joseph McInerney. [JAX]

The American Society of Human Genetics (ASHG) and The Jackson Laboratory (JAX) said today they have launched a new collaboration to produce and deliver educational programs designed to integrate genetic and genomic advances into clinical healthcare practice.

The programs will educate groups such as students and trainees, primary care and other physicians, nurses, pharmacists, physician assistants, and social workers, both organizations said.

ASHG and JAX will build upon more than a half century of joint educational efforts. For more than 50 years, ASHG members and JAX faculty have jointly organized and taught the annual two-week “Short Course on Medical and Experimental Mammalian Genetics,” conducted at JAX’ main campus in Bar Harbor, ME.

The new effort is intended to allow JAX and ASHG to further coordinate their educational activities by developing complementary programs while avoiding duplication.

The first joint ASHG-JAX educational program is scheduled for November, and will educate primary care physicians on cancer genetic testing. The program will take place at the new Jackson Laboratory for Genomic Medicine in Farmington, CT.

“The faculty and members of our two organizations are the individuals conducting the latest research into genetics and human health and disease. This collaboration will allow us to combine their areas of expertise and reach larger audiences than ever before,” Joseph D. McInerney, ASHG’s evp, said in a statement.

McInerney and Edison Liu, M.D., JAX’ president and CEO, led executives from both organizations in signing a Memorandum of Understanding to launch their collaboration.

Added JAX trustee and ASHG past president David Valle, M.D., the Henry J. Knott Professor and Director of the Institute of Genetic Medicine at the Johns Hopkins University School of Medicine: “This is an exciting and vital educational partnership to advance the integration of genetics and genomics into medicine at this critical time.”


NGS and Cancer Biomarker Market Metrics

Enal Razvi, Ph.D., and Gary M. Oosta, Ph.D.

Tuesday, June 10, 2014

The declining costs of NGS are the key driver for its utilization in the clinical setting. [genome.gov]

This report represents qualitative and quantitative metrics of the next-generation sequencing (NGS) landscape and frames it into the context of various biomarker classes.

Highlights of this report:

  • The NGS field is expanding and its quantitative penetrance into clinical testing is growing.
  • We present in this report some data illustrating the various disease classes into which NGS-based testing is penetrating—of course oncology is the leader in this space, but other disease classes are being impacted, too.
  • We also present here our analysis of the cancer biomarkers publications landscape, which demonstrates the patterns of penetration of specific biomarker(s) into various cancer classes—this provides the “starting material” for NGS panels that could be designed and validated on clinical samples as a means to develop NGS-based LDTs for different cancer classes.
  • Taken together, these results frame the market trends of NGS traversing from the research community toward clinical deployment and furthermore offer insight into how NGS-based tests may be developed in large numbers and then tested on patient populations to establish their validity and utility.

Click here to download the PDF report.


CGI to Perform Cancer Dx Testing in Central America, Caribbean for AstraZeneca

Monday, June 09, 2014

Source: © Guillaume Le Bloas - Fotolia.com

AstraZeneca CAMCAR, a division of AZ that serves Central American and Caribbean countries, has tapped Cancer Genetics (CGI) to provide diagnostic testing based on biomarkers for cancer. CGI will perform complex testing for diagnosis and prognosis of cancer patients in Central America and the Caribbean. Per the agreement, CGI will be working closely with AZ-CAMCAR on exploring opportunities to expand into additional geographic territories, more cancer categories, and into select oncology trials.

This partnership, the firms say, will focus on multiple cancer categories starting with lung cancer, as the Pan American Health Organization expects cases and deaths from lung cancer to double in Latin America by 2030.

"We believe our ability to provide accurate, state-of-the-art biomarker-based testing was a key factor in AstraZeneca’s decision to partner with us, and serves as a testament to the growing global awareness of the value of our brand." CGI's CEO Panna Sharma said in a statement. "We are committed to positively impacting cancer care globally, and this relationship serves as another major milestone in fulfilling that mission."

Also as part of that mission, last month CGI picked up India-based company BioServe Biotechnologies for about $1.9 million with the aim of helping CGI scale up its genetic analysis, bioinformatics, and manufacturing operations while capitalizing on clinical diagnostics and trial growth in India and the Asian market.


PerkinElmer Launches Newborn Screening Program in China

Wednesday, June 04, 2014

PerkinElmer entered an agreement to serve as the exclusive collaborator with China's National Health and Family Planning Commission in developing and implementing an extensive three-year newborn screening training program focused on early detection of life-threatening disorders.

The project is expected to increase adoption and access to newborn screening in the country. It will leverage PerkinElmer's diagnostics technologies and expertise as the company will help to train more than 3,000 doctors, clinicians, and laboratory technicians across 600 rural counties in sample collection, clinical diagnostics, and treatment, as well as site inspection and overall program management.

It will also leverage PerkinElmer's diagnostics offerings to identify disorders in newborn babies, including a thyroid stimulating hormone test, which is used to detect congenital hypothyroidism. In addition, the program will offer a test for phenylketonuria, a condition in which a baby is born without the ability to properly utilize phenylalanine, which can damage the central nervous system and the brain.

PerkinElmer plans to work closely with the National Maternal and Children Health Surveillance Office, the program's administrator, to implement this health program.


Mass Spectrometry: Transition from Research to Clinic

Enal Razvi, Ph.D.

Tuesday, June 03, 2014

This report documents the instances where mass spectrometric-based detection has been used in developing in vitro diagnostics. [University of Tennessee Health Science Center]

The focus of this GEN Market & Tech Analysis report is our continuing coverage of this mass spectrometry space as its translating from research to clinic.

Highlights:

  • This report represents our fourth in this series wherein GEN documents the evolution of mass spectrometry from the research space toward deployment as a diagnostics tool.
  • In this report we document the instances where mass spectrometric-based detection has been utilized in the development of in vitro diagnostics (IVDs).
  • Also presented herein are the instances where mass spectrometric-based detection (readout) is being utilized in the microbiology space.
  • Taken together, these instances represent the market segments wherein mass spectrometry has made a successful transition from research to the clinic—i.e., toward clinical diagnostics.

Click here to download the PDF report.


Top 14 Molecular Diagnostics Firms

Monday, June 02, 2014

MDx is a growing market, with a growing number of players. [© Mopic - Fotolia.com]

Molecular diagnostics has grown to a sizeable market, though consensus has proven elusive when it comes to how sizeable. One report released in March offered a market size of $4.476 billion for last year (Grand View Research), while another pegged the market even higher in 2013 at $5.5 billion (Kalorama Information). The latter is more in line with Frost & Sullivan’s 2012 forecast that molecular diagnostics will grow this year to more than $6.2 billion in total revenues (Frost & Sullivan).

Whatever the size, molecular diagnostics is a growing market, with a growing number of players—not only biopharma giants like Roche and Abbott, but numerous companies that have found their niches in tools and technologies. They are expected to be joined by up-and-comers such as Xagenic, which on May 20 was honored with the 2014 North America Frost & Sullivan Award for New Product Innovation Leadership for its fully automated diagnostic platform, designed to enable widespread decentralized testing to be performed outside of clinical laboratories. Xagenic has raised more than $30 million in financing since 2012, of which $20 million in Series B funding was announced in December.

Following is a list of 14 top public molecular diagnostics companies ranked by revenue reported in 2013, either companywide or for molecular diagnostics operations in the case of companies with broader operations.

Two public giants with a presence in molecular diagnostics could not be ranked. Siemens disclosed that the “diagnostics” business of Siemens Healthcare generated $5.383 billion (€3.942 billion) in revenue, but does not offer a breakdown of that sum that would reveal how much of that total reflected molecular diagnostics activity. One possible clue may be found in the $500 million price that bankers representing Siemens were rumored to have asked would-be buyers for the German conglomerate’s microbiology unit, according to a March 19 Reuters report for which Siemens declined comment.

Also not ranked was GE Healthcare, which during a March 18 investor presentation by its president and CEO John Dineen disclosed that it generated $3.7 billion in global orders from “molecular medicine” customers in 2013, without disclosing actual revenue. Even if all those orders did go through, it may not offer a complete picture of the size of GE’s molecular diagnostics business, since the company includes “molecular imaging” not in its “molecular medicine” segment, but within the $9.5 billion “diagnostic and clinical equipment” segment of its Diagnostics business.

#14. Agendia
Revenue: $15 million in 20121

#13. Foundation Medicine
Revenue: $29.2 million

#12. bioMérieux
Revenue: $106.5 million (€78 million)2

#11. Grifols
Revenue: $177.991 million (€130.339 million)3

#10. Genomic Health
Revenue: $261.6 million

#9. Cepheid
Revenue: $401.3 million

#8. Abbott Laboratories
Revenue: $473 million4

#7. BD (Becton, Dickinson & Co.)
Revenue: $606 million5

#6. Myriad Genetics
Revenue: $613.2 million for fiscal year ended June 30, 2013

#5. Qiagen
Revenue: $651 million6

#4. Agilent/Dako
Revenue: $750 million7

#3. Hologic
Revenue: $1.156 billion for fiscal year ending September 28, 20138

#2. Illumina
Revenue: $1.421 billion

#1. Roche
Revenue: $1.756 billion (CHF 1.571 billion)9

Figures in non-U.S. currencies converted to U.S. dollars on May 23 via www.xe.com.

To see this article’s footnotes, click here.


Exome Sequencing May Miss Pathogenetic Variants

Kevin Mayer

Monday, June 02, 2014

Source: © Gernot Krautberger - Fotolia.com

While a patient may unknowingly skirt unseen dangers, like a latter-day Magoo blindly wandering past open manholes, physicians would rather patients be aware of their health risks, or at least have some notion of the degree to which confidence in their wellbeing is justified. A physician, for example, might hesitate before informing a patient of incidental genetic findings from an exome sequencing report.

Such reports, a new study maintains, often fail to produce high-quality results. In particular, currently available exome sequencing kits tend to miss variants in specific genes, including the 56 genes considered clinically relevant by the American College of Medical Genetics and Genomics (ACMG). According to the ACMG, incidental pathogenic findings among these 56 genes should be reported.

The ACMG recommendation, reasoned researchers based at Thomas Jefferson University, assumes that exome sequencing returns data of sufficient quality. Data of poor quality, however, might instill false confidence, much like Magoo’s gauzy outlook. While the fictional Magoo invariably escapes the consequences of his blurry vision, or his obstinate refusal to see that he has a problem, real-life patients might suffer harm if medical professionals were to miss chances to identify (and correct) shortcomings in genomic testing.

To address this issue, the researchers surveyed the potential false-negative rate of mutations in the 56 ACMG genes. They retrospectively analyzed 44 exome datasets from four different exome capture kits and two-sequence platforms. In addition, the researchers examined the exome methods for their ability to detect clinically relevant mutations in the 56 ACMG genes.

A total of 17,774 pathogenic nucleotide variants are annotated in the Human Gene Mutation Database (HGMD) for the 56 genes, and data were examined for depth of coverage in the exome datasets.

The researchers presented their findings June 1 at the annual conference of the European Society of Human Genetics, in a paper entitled “Clinical exome sequence performance for reporting secondary genetic findings.” The paper was read by Eric Londin, Ph.D., assistant professor in the Computational Medicine Center, Department of Pathology, Anatomy, and Cellular Biology, Thomas Jefferson University.

Overall, the four-exome methods had inadequate depth of coverage for accurate base calling ranging from 5.2 to 34.8% of the pathogenic variant positions. “At least one gene in each exome method was missing more than 40% of disease-causing genetic variants,” said Dr. Londin. “And we found that the worst-performing method missed more than 90% of such variants in 4 of the 56 genes.”

A central question, the researchers asserted, is not how often a clinical diagnosis can be made using exome sequencing, but how often it is missed, and the study shows clearly that there is a high false-negative rate using existing sequencing kits.

“Our concern is that when a clinical exome analysis does not report a disease-causing genetic variant, it may be rather that the location of that variant has not been analyzed rather than the patient’s DNA being free of a disease-causing variant,” continued Dr. Londin. “Depending on the method and the laboratory, a significant fraction (more than 10%) of the exome may be untested.”

One potential improvement would be the development of new kits and methods that provide adequate and reliable coverage of genes with known disease associations. “If adequate performance cannot be obtained across the exome,” commented Dr. Londin, “then further use of targeted disease-specific panels of genes should be explored.”

Another potential improvement would be the generation of sufficiently large amounts of sequence data to achieve optimum nucleotide coverage. “Current consensus and regulatory guidelines do not prescribe a minimum data requirement for clinical exome tests. The result is that when a causative variant cannot be identified, it does not necessarily imply that the variant is not present,” emphasized Dr. Londin. “In other words, a clinical ‘whole exome’ study may not be ‘wholesome’ in coverage.”

While the study includes suggestions about ways to improve clinical exome sequencing, it has more immediate import. Specifically, it raises concerns about rates of false-positive results. As Dr. Londin concluded, “Patients and their families should be made aware of this problem and of the implications of the genomic findings of clinical exome sequencing in its current state.”


A Common Sense Discussion of Patenting Medical Diagnostics

Brian D. Coggio, J.D.

Thursday, May 29, 2014

Ariosa Diagnostics was one of the winners after a federal judge invalidated a Sequenom patent covering a noninvasive method of detecting Down syndrome in fetuses. [© Gennadiy Poznyakov - Fotolia.com]

A woman learns she is pregnant. After the excitement subsides, she wonders: “Will my child be healthy?” or “Will the baby have a birth defect?” Her husband, parents, and siblings also wonder. One or more prayers may be offered. Indeed, if a history of genetic anomalies exists, concerns are exacerbated. During pregnancy, if certain physical observations indicate that the child may have, e.g., Down syndrome, or other possible problems, what should she do? The options were limited. Prenatal screening is possible. But this only estimates the chance that a child will have Down syndrome, the most common birth defect in the United States. It is hardly definitive in providing results to the parents to allay their concerns. Diagnostic tests are also a possibility. While the results of amniocentesis or chorionic villus sampling are more definitive, the tests are particularly invasive and can result in the spontaneous termination of the pregnancy, i.e., a miscarriage. These were essentially the only options available to the future parents.

Recently, however, a new blood test offers pregnant women a safe and much more accurate way to screen for, inter alia, Down syndrome. A confirmatory amniocentesis may still be required in certain cases, but the new test would send far fewer women for that risky procedure. As a result, miscarriages would be reduced. In addition, pregnant women will not suffer the anxiety from false positives that are much more common with existing tests. Indeed, data from one medical center demonstrate that the “positive predictive value” of the new test is ten times greater than standard tests. Another well-known research organization has called the test a “major advance.”

For the rest of the story click here.


Harnessing the Power of Exosomes

Johan Skog, Ph.D.

Thursday, May 29, 2014

A primary glioblastoma cell releasing exosomes. [Exosome Diagnostics]

Exosomes are lipid nanovesicles, on the order of 30–200 nm, secreted from cells and found in all bodily fluids such as plasma, urine, and cerebrospinal fluid (CSF). Although exosomes were discovered over 30 years ago, they were originally thought to be nothing more than a garbage disposal system for cellular debris and proteins.

More recently, interest in exosomes has increased with better understanding of their capabilities.  In 2003 there were approximately 30 PubMed referenced articles on exosomes, while in the three years into 2011 there were almost 350. Much of the excitement is being generated from the potential to utilize exosomes in the development of biofluid-based, real-time molecular diagnostics, their potential as drug delivery vehicles, and as tools for biomedical research.

For the rest of the story click here.


Labs Face Medicare Cuts, New Codes

Alex Philippidis

Thursday, May 29, 2014

PAMA will force labs and providers to implement new test coding systems that will add potentially thousands of new codes. [© Lisa F. Young – Fotolia.com]

It’s not an exaggeration to say the new Protesting Access to Medicare Act (PAMA) marks the biggest change for clinical labs since the Clinical Laboratory Improvement Amendments of 1988 (CLIA).

Harder to assess is whether the reality of implementing PAMA will match the most pessimistic predictions that the new law will drive smaller labs and healthcare providers out of business.

Congress focused on forestalling imminent cuts to Medicare reimbursements when it passed HR 4302, signed April 1 by President Barack Obama. PAMA postpones until March 31, 2015, cuts estimated at 24% to the Sustainable Growth Rate (SGR) formula, which was to run out in March.

But PAMA gives labs and providers much more cause for concern, with new rules for phasing in reimbursement cuts, and new procedures to set rates. The new law will also force labs and providers to implement new test coding systems that will add potentially thousands of new codes.

For the rest of the story click here.


Cancer Diagnostics Leverage Decreasing Cost of Sequencing

Chris Anderson

Thursday, May 29, 2014

Highly invasive biopsies may soon be a relic of the past as researchers develop blood, urine, and cerebrospinal diagnostic techniques. [Angellodeco/Deposit Photos]

The cancer diagnostic landscape has evolved significantly since the first companion diagnostic was launched to detect overexpression of the HER2 gene in breast cancer and thus indicate whether a patient would be highly likely to respond to trastuzumab (Herceptin) treatment. Since then, and over the course of the last decade, companion diagnostics that focused on a single distinctive molecular marker for a specific cancer have been used to both inform the development of relevant therapeutic targets and determine whether individual patients would respond favorably to a therapeutic. The development of these diagnostics was the first step to unraveling the sticky question of why some patients showed great improvement when prescribed a cancer medication while others showed no response at all.

In the mid to late 2000s, cancer diagnostics moved to gene expression profiling. These tests don’t determine the likelihood of response to a particular drug, rather they stratify patients based on the likelihood their cancer will recur after initial treatment. The most successful diagnostics, Oncotype DX from Genomic Health and MammaPrint from Agendia, target breast cancer and are today used to help determine how aggressively to treat the cancer based on each patient’s risk.

For the rest of the story click here.


Clinical OMICs Issue 4 Now Available

Thursday, May 29, 2014

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

Clinical OMICs Issue 4


Two Independently Drawn Maps of the Human Proteome Show Similar Contours

Kevin Mayer

Wednesday, May 28, 2014

Using mass-spectrometry-based proteomics, researchers have generated comprehensive draft maps of the all proteins in the human body and made their results available. [H. Hahne/TUM, BioJS]

The history of science is replete with instances of multiple discovery—the more or less simultaneous announcement of essentially the same breakthrough by independent researchers. Still, it may still seem uncanny that two separate research groups not only produced a draft map of the human proteome, they also published their results the same day in the same journal.

Today, in the online edition of Nature, researchers from Johns Hopkins University and the Institute of Bioinformatics in Bangalore, India, published an article entitled “A draft map of the human proteome.” Similarly, researchers from Technische Universitaet Muenchen (TUM) published an article entitled “Mass-spectrometry-based draft of the human proteome.”

While the mapping of the human proteome may not prove to be as epochal as the formulation of calculus by Newton and Leibniz, or the development of evolutionary thought by Darwin and Wallace, it is still vitally important. By comprehensively cataloging human proteins, the Baltimore/Bangalore team and the Munich team have created a resource for other researchers that promises to advance personalized medicine.

As stated by the authors of the Baltimore/Bangalore paper, “With the availability of both genomic and proteomic landscapes, integrating the information from both resources is likely to accelerate basic as well as translational research in the years to come through a better understanding of gene-protein-pathway networks in health and disease.”

The dual papers seem a little less coincidental when one considers that both research groups faced similar challenges and exploited similar technologies. As a result, they were almost fated to enact similar strategies and uncover similar findings.

Studying proteins is far more technically challenging than studying genes because the structures and functions of proteins are complex and diverse. Moreover, a mere list of existing proteins would not be very helpful without accompanying information about where in the body those proteins are found. Most protein studies to date have focused on individual tissues, often in the context of specific diseases.

To address these challenges, both research teams took advantage of mass spectrometry, which has revolutionized proteomics studies in a manner analogous to the impact of next-generation sequencing on genomics and transcriptomics. In addition, both teams compiled information about the types, distribution, and abundance of proteins in various cells and tissues. For example, the Baltimore/Bangalore team conducted in-depth profiling of 30 histologically normal human samples, including 17 adult tissues, 7 fetal tissues, and 6 purified primary hematopoietic cells.

While working up their dataset, the Baltimore/Bangalore team identified proteins encoded by 17,294 genes, which is about 84% of all the genes in the human genome predicted to encode proteins. The Munich team reports that it cataloged over 18,000 proteins.

The Baltimore/Bangalore team indicated that it had identified 193 novel proteins that came from regions of the genome not predicted to code for proteins, suggesting that the human genome is more complex than previously thought. Similarly, the Munich team noted that it had discovered “hundreds of protein fragments that are encoded by DNA outside of currently known genes.” These new proteins may possess novel biological properties and functions.

Both teams cited the challenge of “missing proteins”—proteins that should exist, given what we know about the genome, but remain unobserved. “The depth of our analysis enabled us to identify protein products derived from two-thirds (2,555 out of 3,844) of proteins designated as missing proteins for lack of protein-based evidence,” wrote the Baltimore/Bangalore researchers. “Several hypothetical proteins that we identified have a broad tissue distribution, indicating the inadequate sampling of the human proteome thus far.” The Munich researchers speculated that some missing proteins may exist only during embryonic development. These scientists also suggested that many known genes have simply become nonfunctional, such as genes believed to code for olfactory receptors—an indication that modern humans no longer rely on a sophisticated sense of smell to survive.

Yet another parallel finding concerned housekeeping proteins, which are highly abundant; well represented among histones, ribosomal proteins, metabolic enzymes, and cytoskeletal proteins; and constitute about 75% of total protein mass. The Munich team reported finding around 10,000 such proteins “in many different places.” Similarly, in their article, the Baltimore/Bangalore team noted that it “detected proteins encoded by 2,350 genes across all human cells/tissues.”

“One of the caveats of tissue proteomics is the contribution of vasculature, blood, and hematopoietic cells,” it added. “Thus, proteins designated as housekeeping proteins based on analysis of tissue proteomes could be broadly grouped into two categories, those that are truly expressed in every single cell type and those that are found in every tissue (for example, endothelial cells).”

Both groups highlighted the importance of their work for speeding research and translational developments. For example, the Munich team examined 24 cancer drugs whose effectiveness against 35 cancer cell lines were found to correlate strongly with their protein profiles. According to Prof. Bernhard Küster, the TUM Chair of Proteomics and Bioanalytics, “This edges us a little bit closer to the individualized treatment of patients. If we knew the protein profile of a tumor in detail, we might be able to administer drugs in a more targeted way. The new insights also allow medical researchers to investigate combinations of drugs and, thereby, tailoring treatments even more closely to a patient's individual needs.”

The Baltimore/Bangalore team emphasized the importance of using direct protein sequencing technologies such as mass spectrometry to complement genome annotation efforts. In addition, it outlined several proteomic research strategies that could benefit from the sampling of individual cell types of human tissues and organs and the ultimate creation of a “human cell map.”

“You can think of the human body as a huge library where each protein is a book,” said Akhilesh Pandey, M.D., Ph.D., a professor at the McKusick-Nathans Institute of Genetic Medicine and of biological chemistry, pathology and oncology at the Johns Hopkins University and the founder and director of the Institute of Bioinformatics. “The difficulty is that we don’t have a comprehensive catalog that gives us the titles of the available books and where to find them. We think we now have a good first draft of that comprehensive catalog.”

Committed to helping other researchers identify the proteins in their experiments, the Baltimore/Bangalore team has made its human proteome catalog available as an interactive web-based resource at www.humanproteomemap.org. Similarly, the Munich team, together with software company SAP, has made its inventory freely available at www.proteomicsdb.org.


Warring with Cancer Avatars to Expose Unique Vulnerabilities of Real Tumors

Kevin Mayer

Wednesday, May 21, 2014

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Cancer avatars, much like avatars in video and computer games, may become dynamic characters, not just collections of visual features. If cancer avatars are developed on the basis of genomic profiles, they can reflect the signaling and metabolic complexities of real cancers. What’s more, a cancer avatar, set loose in a virtual world—call it TumorSpace—may interact with different adversaries—drugs, say—and experience different fates. A crushing defeat would be cause for celebration, for playing with a cancer avatar is more than a game. It could reveal which drugs would be most effective in helping real patients.

Researchers fully aware of how computer simulations may inform personalized medicine have developed a virtual cell that achieves a kind of Jekyll-to-Hyde transformation. At first, the virtual cell has the internal workings of a normal, healthy cell. Then, the virtual healthy cell can be made cancerous. Indeed, it can be turned into any kind of cancer cell by distorting specific points and pathways in the system.

These cellular distortions represent a person’s cancer avatar. Once the avatar is generated, a computer model predicts which drugs, based upon their known functions, are most likely to kill a real cancer cell.

This approach to tumor modeling has been developed by researchers at the University of California, San Diego School of Medicine and Moores Cancer Center. They generated cancer avatars for cells obtained from patients with glioblastoma, a highly aggressive cancer of the brain’s glial cells. After generating predictions of which drugs would be most effective, the researchers “truth checked” their predictions  against standard, cultured cells in drug-sensitivity experiments.

The researchers published their work May 21 in the Journal of Translational Medicine, in an article entitled “In silico modeling predicts drug sensitivity of patient-derived cancer cells.” The researchers explained that they began by probing the results from a recent hypothesis-independent, empirical study by Garnett and co-workers that analyzed the sensitivity of hundreds of profiled cancer cell lines to 130 different anticancer agents. They then used the tumor model to predict the sensitivity of patient-derived GBM cell lines to different targeted therapeutic agents.

“Among the drug-mutation associations reported in the Garnett study, our in silico model accurately predicted ~85% of the associations,” wrote the authors. “While testing the model in a prospective manner using simulations of patient-derived GBM cell lines, we compared our simulation predictions with experimental data using the same cells in vitro. This analysis yielded a ~75% agreement of in silico drug sensitivity with in vitro experimental findings.”

“Genomics tells us that cancers are a lot like snowflakes. No two cancers are alike so it does not make sense to give all patients the same drugs. This is the idea behind personalizing therapies for cancer," said lead author Sandeep Pingle, M.D., Ph.D., a project scientist in the laboratory of Santosh Kesari, M.D., Ph.D., chief of the division of Neuro-Oncology, professor in the department of neurosciences, director of Neuro-Oncology at UC San Diego Moores Cancer Center and the study's senior author.

“With the virtual cell model, we can take into account all the complexity of cellular processes to predict which drugs will be the most effective against a particular tumor based on its genomic profile," Dr. Pingle added. “This is a first step toward personalized medicine.”


Memorial Sloan Kettering Receives $100M Gift toward Precision Oncology Center

Tuesday, May 20, 2014

Memorial Sloan Kettering Cancer Center’s physician-in-chief José Baselga, M.D. (left), with Marie-Josée Kravis, chair of the board of the Sloan Kettering Institute (center) and Henry R. Kravis, investor and philanthropist (right). [Business Wire]

With a little help from Sloan Kettering Institute chair Marie-Josée Kravis and her husband, philanthropist Henry R. Kravis, the Memorial Sloan Kettering Cancer Center (MSK) is launching a new program that it says will reshape clinical trials and speed up translation of molecular discoveries into routine clinical practice. Dubbed the Marie-Josée and Henry R. Kravis Center for Molecular Oncology (CMO), the new center will support development of individualized cancer therapies and diagnostics. The couple donated $100 million toward its founding.

The CMO, according to MSK, will include around 20 labs and support over 100 MSK faculty and staff. It will also contain two next-generation sequencing (NGS) facilities, one of which will sequence patient samples in real time, while the other focuses on discovering new genetic alterations and therapeutic targets. MSK says new lab space is currently under construction, and it is buying new instrumentation for generating and analyzing large-scale genomic data for the new center. MSK hopes the CMO will not only bring together existing researchers, but recruit new ones as well.

MSK has big plans for the CMO: Sloan Kettering hopes to use it to analyze over 10,000 patient tumors in its first year alone and ultimately aims to offer molecular analysis for all cancer types for every patient at MSK. The CMO will profile archived tumor specimens and tissues from trials with NGS and other technologies, then correlate the molecular information of each tumor with clinical outcomes to get a better view of how genetic alterations affect tumors and come up with personalized treatments based on this knowledge. One of the CMO's cornerstones, MSK adds, will be "basket studies", Phase I trials where patients whose tumors test positive for certain mutations regardless of cancer type are offered new therapies. The CMO will also analyze the tumors of exceptional responders, or patients who experience a sustained response to treatment in a trial where nearly all the other participants do not.

"Throughout the course of my involvement at Memorial Sloan Kettering, I have been deeply impressed by the dedication, experience, and competence of the physicians and scientists who are working to unravel the complexities of cancer," Marie-Josée Kravis, who has also been a member of MSK’s Boards of Overseers and Managers since 2000, said in a statement. "Henry and I are delighted to support this exciting new initiative, which offers such hope to people around the world."


WEBINAR—Clinically Actionable Genomics: From Sequencing to Personalized Medicine

Monday, May 19, 2014

Appistry's CSO Richard Mazzarella, Ph.D., and Cancer Genetics' Molecular Diagnostics Director Weiyi Chen, Ph.D., will be speakers.

Genome sequencing, massive amounts of genetic data, bioinformatics, and associated analytics are rapidly redefining clinical practice, particularly in oncology. All this represents a major and significant step forward in the evolution of personalized medicine.

This webinar, taking place Thursday, May 29, 2014 at 1:00 pm ET (10:00 am PT), will focus on describing those technologies and strategies that are transforming genomic data into clinically actionable intelligence. Specific examples of how such data has enabled the validation of therapies for one type of cancer will be illustrated. In addition, it will also be shown how these same validated therapies can be used to treat another form of the disease. Also under discussion will be the current and future role of novel molecular diagnostics in clinical oncology.

WHO SHOULD ATTEND:

  • Pathologists
  • Oncologists
  • Cancer drug developers
  • Clinical laboratory scientists

Click here to register


A Global Phosphorylation Assay

Ian Pike and Emma Lahert

Friday, May 16, 2014

The use of targeted agents against key signaling kinases is transforming cancer treatment. Drugs such as Herceptin and Zelboraf have increased progression-free survival in breast cancer and melanoma respectively and are far from the only examples. However, the complexity of signaling pathway networks allows tumor cells to adapt under monotherapy using alternative pathways to maintain a proliferative phenotype. Such resistance mechanisms may be inherently present at the onset of treatment (de novo resistance) or may develop in response to the treatment (acquired resistance). This has led researchers to call for the use of more comprehensive analysis of signaling pathways to identify resistance pathways, and to then use this knowledge to select precise combinations of drugs matched to the individual tumor profile.

Regulation of pathway activity is achieved through precisely timed gene expression overlain with the more subtle regulation of post-translational modifications such as phosphorylation, glycosylation, and ubiquitination. While genomic tools such as RNAseq and next-generation sequencing may demonstrate gross changes in signaling networks, only a comprehensive analysis of protein post-translational modifications, particularly phosphorylation, across thousands of pathway proteins, can provide the required biological information to enable selection of the most appropriate drug combination and switching of therapies.

For the rest of the story click here.


Promoting Wellness and Demystifying Disease: The 100K Project

Leroy Hood, M.D., Ph.D., and Nathan D. Price, Ph.D.

Friday, May 16, 2014

We believe that a longitudinal, Framingham-like study of 100,000 well individuals (hereafter termed the 100K project) and their dynamical data clouds could transform medicine by 1) providing scientifically validated metrics for wellness, 2) allowing one to study the earliest origins of disease in an individual and 3) allow one to follow the entire progression of a disease from its beginning to end.

This proposal would allow us to study the initiation and progression of all common diseases and, from that, learning how to predict and prevent these diseases would revolutionize healthcare.

Complexity, Disease, and Systems Medicine

Contemporary medicine is challenged by the incredible complexity of physiology and disease. Each individual has unique genetic and environmental contexts. Clearly the traditional reductionist approaches to disease are insufficient to effectively deconvolute this complexity. Over the last 10 years systems approaches have increasingly been employed, leading to a new discipline designated systems medicine, which has two striking features.

For the rest of the story click here.


N-of-One Tapped to Interpret OncoDNA's NGS Tests

Friday, May 16, 2014

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N-of-One inked an agreement with Belgian personalized medicine firm OncoDNA under which it will provide clinical interpretation for all of OncoDNA's next-generation sequencing (NGS) and other molecular tests for patients throughout Europe, the Middle East, and other parts of the world.

OncoDNA provides tumor profiling services designed to help medical doctors choose treatments and monitor tumor evolution. N-of-One's clinical interpretation, OncoDNA says, can provide biological and clinical knowledge and insights related to a tumor's mutation profile, linking this knowledge to therapeutic strategies including clinical trials. In a statement, Jean-Pol Detiffe, OncoDNA's CEO, added that, in addition to clinical interpretation, N-of-One was tapped for its ability to integrate different types of molecular test results into a single report rapidly.

"OncoDNA's industry-leading, molecular diagnostic solutions, coupled with N-of-One's deep expertise in clinical interpretation in oncology, will enable broader patient access worldwide to personalized cancer treatment in a scalable, cost-effective manner," commented N-of-One's CEO Chris Cournoyer.

Back in March, N-of-One teamed up with genomics visualization and analysis software developer BioDiscovery to provide integrated genomic analysis interpretation solutions. It inked a similar deal with Appistry in February to provide genetic sequencing data analysis and molecular interpretation services.


Clinical OMICs Issue 3 Now Available

Thursday, May 15, 2014

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

Clinical OMICs Issue 3


What to Look for in a Clinical Next-Generation Sequencer

Shawn C. Baker

Thursday, May 15, 2014

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Next-generation sequencing (NGS) has been making tremendous strides in the research market and with Illumina’s recent launch of the HiSeq X Ten, we’ve essentially reached the $1,000 genome (notwithstanding quibbles over what exactly should be accounted for in the $1,000). With these advancements, the pull to adapt NGS for the clinical market has gotten stronger. The first examples of how this technology will transform medicine are already showing up.

The press has been filled with stories, sometimes heart-warming and sometimes gut wrenching, of NGS being used in the diagnosis of late-stage cancers and rare childhood diseases. But while these examples show how NGS can be used to treat patients, they aren’t really examples of clinical sequencing. These are still research projects, each one requiring the attention of multiple experts poring over the data to come up with hypotheses of how to treat the underlying malady. In order for NGS to be considered a true clinical tool, it will have to be used on a routine basis, replacing older genetic-based tests. This transition is starting to happen for prenatal testing and cancer diagnostics.
 

For the rest of the story click here.
 


Bringing Informed Interpretation to Vexing Variants

Alex Philippidis

Thursday, May 15, 2014

While the first traffic light flashed 18 years before the first car was built, the rules of the road have long lagged behind technology where genetic testing is concerned, especially in distinguishing functional gene variants from those that cause disease.

That is starting to change as groups of researchers and clinicians hammer out guidelines for statistically rigorous and evidence-based clinical interpretation of variants found through next-generation sequencing.

On April 23, a working group of 27 experts in genomic research, analysis, and clinical diagnostic sequencing convened in a 2012 workshop by the NIH’s National Human Genome Research Institute (NHGRI) published an open-access paper in Nature presenting its proposed guidelines for evaluating evidence supporting variant causality.

Daniel MacArthur, Ph.D., of Massachusetts General Hospital and Chris Gunter, Ph.D., of Marcus Autism Center and Emory University, led the working group in drawing up guidelines that cover evidence assessment for candidate disease genes and candidate pathogenic variants, as well as standards for reporting, publishing, and even sharing data.

The group listed priorities for research and infrastructure development: Developing standardized, quantitative statistical approaches for assigning probability of causation; large-scale genotyping of reported disease-causing variants; building public databases of those variants, with up-to-date supporting evidence, plus variant and allele frequency data from large, diverse population samples; and greater sharing of data by research and clinical labs.

For the rest of the story click here.


Future Cancer Care: Anticipating “Panomics” with Bioinformatics

Patricia Fitzpatrick Dimond, Ph.D.

Thursday, May 15, 2014

In 2009 Mark Boguski and colleagues published a paper entitled “Customized care 2020: how medical sequencing and network biology will enable personalized medicine.” In the paper the authors described a model incorporating these pathways, annotation of disease networks and drug targets, and simulation of therapeutic interventions with virtual drugs or with combinations of them.

The pathology report of the future, the authors said, will provide precision diagnoses that are at the core of personalized medicine and will be an interactive software tool for clinical teams to design a customized care regimen and monitor its efficacy during treatment.
Beyond cancer, noted Zhu et al. in their 2007 paper in Plos Computational Biology, molecular dissection of diseases such as obesity and diabetes will require a systematic approach to show how genes interact with one another, and with genetic and environmental factors.

For the rest of the story click here.

 


Cancer Genetics Acquires BioServe India

Thursday, May 15, 2014

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Cancer Genetics said today it acquired Indian-based BioServe Biotechnologies for about $1.9 million, primarily in stock and other deferred payments, in a deal designed to help the buyer scale up its genetic analysis, bioinformatics, and manufacturing operations while capitalizing on clinical diagnostics and trial growth in India and the Asian market over recent years. 

BioServe India will become a wholly owned Cancer Genetics subsidiary to be renamed Cancer Genetics India (CGI).

CGI said it plans on retaining all 26 current employees of BioServe India, while further expanding and strengthening its sales and clinical teams in India, which are based at a 14,000-square-foot genomics facility in Hyderabad.

In acquiring BioServe India, CGI said, it is looking to offer oncology-focused next-generation sequencing and CGI’s proprietary cancer portfolio as strategic drivers of growth in India. The acquiring company is also looking to help clients with clinical trials in India or Asia, since the market has experienced a combined annual growth rate of 30% to 40% percent over recent years.

CGI added it plans to gain Clinical Laboratory Improvement Amendments of 1988 (CLIA) certification for BioServe India’s Hyderabad based lab “in the coming quarters.”

“With this acquisition, CGI is now better positioned to increase our global presence in personalized cancer care and further improve outcomes and lower costs for cancer patients,” Cancer Genetics CEO Panna Sharma said in a statement. “The infrastructure and enhanced capacities in next generation sequencing for oncology accelerate our development plans while positioning us to make more effective use of our capital.”

Sharma said CGI’s acquisition of BioServe India would not affect company earnings per share this year, while adding revenue in 2015: “It has the potential to accelerate our next generation sequencing development, improve our gross profit margins, and diversify our revenue growth outside the U.S.”

CGI announced the acquisition on the day it also released its first-quarter financial results. The company cut its net loss by 20% or $500,000, to $2.4 million, on revenue that rose 17%, to $1.4 million. Total first quarter test volume increased 45%, to 2,772 tests, CGI said.

BioServe India is a molecular kit manufacturer and provider of genomics services that include next-generation sequencing genotyping and DNA synthesis—services designed to help researchers identify genetic markers, validate drug targets and correlate clinical and molecular data to accelerate the development of new and effective drugs.

The company said its nearly 200 clients include Dr. Reddy’s Laboratory, the Indian Institute of Science Education & Research, and the Centre for Cellular and Molecular Biology.

BioServe India has also positioned itself to improve oncology diagnostics care and management throughout India by growing its clinical diagnostics capabilities in oncology and next-generation sequencing.

The new subsidiary will integrate CGI’s DNA probe manufacturing and proprietary FHACT™ test into the Indian market, which accounts for more than 25% of global deaths attributed to cervical cancer.

FHACT is a noninvasive genomic test that can work as a reflex test from a Pap smear and can identify cancer and precancer lesions caused by persistent human papillomavirus (HPV) infection. The test is designed to assist physicians by furnishing key information for making treatment decisions in cervical and HPV-related cancers.

BioServe India has the financial backing of VenturEast, a healthcare-focused venture capital fund manager based in India with close to $300 million under management.


System-Wide Map of Genetic/Metabolomic Connections Released

Kevin Mayer

Monday, May 12, 2014

If a genetic variant is the origin and a disease the destination, the biochemical path between them may appear on a map of a sprawling genetic/metabolomic network. But that’s just the simplest imaginable use of such a map. Rather than think of a genetic/metabolomic map as a way to trace a single path, as though one were using a transit map to trace an individual’s commute, one might think globally, in terms analogous to those used by traffic managers. For example, what snarls might arise if multiple stations and transfer nodes were to become overloaded?

This approach to analyzing the genetic influences on metabolism, and metabolic diseases, is becoming a reality thanks to projects such as the one recently completed by researchers based at the Wellcome Trust Sanger Institute. These researchers, led by Nicole Soranzo, Ph.D., have compiled an atlas of genetic associations with metabolism that has linked 145 genetic regions with more than 400 metabolites in human blood. This new compendium of associations between genetic regions and metabolite levels provides a powerful tool to identify genes that could be used in drug and diagnostic tests for a wide range of metabolic disorders.

The research team’s results were presented May 11 in Nature Genetics, in an article entitled “An atlas of genetic influences on human blood metabolites.” In this article, the authors wrote: “Our observations suggest widespread genetic control over a large range of different pathways and functions and support the notion of human metabolism as a complex continuum governed by genetic effects of variable intensity, complex regulatory influences and non-genetic effects. Our results advance knowledge in a number of areas of biomedical and pharmacogenetic interest, generating nearly 100 new hypotheses of SNP-metabolite and disease correlates and identifying a large catalog of new potential biomarkers as well as associations to drug targets, transporters and metabolic enzymes.”

“The sheer wealth of biological information we have uncovered is extraordinary” said Dr. Soranzo. “It’s exciting to think that researchers can now take this freely available information forward to better understand the molecular underpinnings of a vast range of metabolic associations.”

As Dr. Soranzo has indicated in her remarks, the information uncovered by the researchers is publicly available. This point was echoed by Gabi Kastenmüller, Ph.D., co-senior author from the Helmholtz Center Munich, Germany: “We developed an open-access database that allows researchers to easily search through the findings, to understand genetic variants associated with metabolism one metabolite at a time and in the context of the complete metabolic network. This database will facilitate drug discovery for metabolic disorders and also help researchers to understand the biology behind disease."

Other associations suggest tantalizing possibilities for further study. For instance, a number of the genetic associations identified involved aromatic acids, such as tryptophan, which are important for brain function. While this study did not measure association of metabolites in the brain, these genetic findings open new avenues to assess potential genetic influences on brain function and responses to drugs that affect brain function, such as antidepressants.

“This work provides an important new window into the genetic variation underlying human metabolism," added Eric Fauman, Ph.D., study co-author and associate research fellow from Pfizer. “Through targeted precision medicine and by linking human disease genes to in vivo biological markers, we hope to enhance our ability to deliver impactful new medicines for patients across a variety of disorders.”


Omics Experts Help Oncologists Scout Individualized Therapies

Tuesday, May 06, 2014

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Like travelers who roam curious lands, oncologists who delve into tumor genetics may find themselves in need of local guides, experts who will put them on the right path. As far as oncologists are concerned, the right path is the one that leads to an effective therapy, but in difficult-to-treat cases, the path to the best treatment plan may diverge from familiar trails, with the twists and turns following the contours of a tumor’s unique genomic landscape.

To make such landscapes less forbidding and the paths through them less tortuous, oncologists may consult with other experts such as basic scientists, geneticists, and bioinformatics scientists. Such a pathfinding exercise has, in fact, been carried out. At the University of California, San Diego Moores Cancer Center, researchers put together an advisory group, a tumor board, to analyze the results of molecular profiles.

As explained by the researchers, who presented their work in the May 5 online issue of The Oncologist, the tumor board convened medical, surgical, and radiation therapy oncologists; biostatisticians; radiologists; pathologists; clinical geneticists; basic and translational science researchers; and bioinformatics and pathway analysis specialists. These multidisciplinary experts were then charged with discussing the intricacies of tumor genetics and tailoring a personalized treatment plan for difficult-to-treat patients. These patients were struggling with advanced cancer, had exhausted standard therapies, or were receiving treatments that physicians feared would become ineffective.

The 34 patients in the study had received a median of three prior therapies. In addition, they had a median of four molecular abnormalities found by next-generation sequencing (182- or 236-gene panels).

“We found 74 genes with 123 aberrations involved in cancer growth,” said Razelle Kurzrock, M.D, director of the Center for Personalized Cancer Therapy at the Moores Cancer Center. “No two patients had the same aberrations, and 107 distinct anomalies were seen only once.”

"Cancer can be different in every patient," added Barbara Parker, M.D., Moores Cancer Center deputy director for Clinical Affairs. “Standard therapy can be very efficient for many patients, but for those who do not respond to conventional treatment, we need to find alternatives that will work for their disease.” In particular, it may be necessary to individualize therapy to a patient’s genetic makeup if that patient does not respond to standard care or appears to have disease that has become drug resistant.

The study, as detailed in “Molecular Tumor Board: The University of California San Diego Moores Cancer Center Experience,” focused on 11 “evaluable” patients whose treatment had been informed by molecular diagnostics: three of these patients achieved partial responses (progression-free survival of 3.4 months, ≥6.5 months, and 7.6 months). The most common reasons for being unable to act on the molecular diagnostic results, noted the study’s authors, were that “patients were ineligible for or could not travel to an appropriately targeted clinical trial and/or that insurance would not cover the cognate agents.”

“We have found that molecular diagnostics play an important role in patient care when paired with the expertise of a molecular tumor board,” said Maria Schwaederle, PharmD, lead author and a researcher in the Center for Personalized Cancer Therapy. “However, the immense complexity of tumors and their genomic aberrations will require sophisticated computer technologies for optimal interpretation.”

In addition to the interpretive challenges posed by next-generation sequencing, there are more mundane if equally consequential difficulties. As indicated in the study’s conclusion, “Barriers to personalized therapy include access to appropriately targeted drugs.”


PerkinElmer Closes Signature Genomics Testing Business

Thursday, May 01, 2014

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PerkinElmer said yesterday it will close its Signature Genomics business in Spokane, WA, and lay off all 80 workers based there, as part of a total shutdown of its cytogenetic testing services. 

The site, described on the company’s website as an array-based comparative genomic hybridization (array CGH) diagnostic laboratory, will shut down later this year. The closing will end 11 years of operation for Signature Genomics, which provides diagnostic genetic testing services using microarrays.

Some 80 people will be idled, The Spokesman-Review newspaper of Spokane reported.

Signature Genomics was the first laboratory to provide microarray-based cytogenetic diagnostics for intellectual disability and birth defects through its SignatureChip, and had grown to 120 employees when it was acquired by PerkinElmer in 2010 for $90 million. At the time, PerkinElmer had hoped to strengthen its position in molecular diagnostics, which it viewed as complementary to its longtime strength in medical equipment.

“Changing market conditions, including a highly unfavorable reimbursement environment, combined with a significant decline in demand for invasive procedures due to the uptake of noninvasive prenatal testing, contributed to this decision,” PerkinElmer said in a statement. “We will focus on assisting Signature Genomics’ employees through this transition and providing our customers with immediate access to alternative providers for microarray testing.”

The statement offered no specific last date of operations.

Signature Genomics was co-founded by Lisa G. Shaffer, Ph.D., and Bassem A. Bejjani, M.D., who established the company as a partnership between Signature Genomic Services, Pathology Associates Medical Laboratories and Sacred Heart Medical Center.

Dr. Shaffer served as president until 2012, when she left to establish Paw Print Genetics, whose lab carries out testing and analysis of canine genetic diseases. Dr. Bejjani left Signature in 2011 and the following year co-founded Revemic Systems, a startup specializing in practical interpretation of genetic test results. His association with Revemic ended last year, according to his LinkedIn page.

On April 24, PerkinElmer reported first-quarter net income of $34.224 million, up 6% from the year-ago quarter, on $531.904 million in revenue, 5% above Q1 2013.


Clinical OMICs Issue 2 Now Available

Wednesday, April 30, 2014

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

Clinical OMICs Issue 2


Poorly Informed Patients More Dubious of Pharmacogenetics

Kevin Mayer

Tuesday, April 29, 2014

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“An educated consumer is our best customer”—so said businessman and philanthropist Sy Syms. While Syms’ business was retail clothing, his slogan is broadly applicable. In fact, according to a recent survey by medical researchers, the clothiers’ wisdom can even guide physicians who hope to introduce their patients to the benefits of pharmacogenetics—the study of how a patient’s genes can affect drug reaction and dosage. Patients, the researchers found, are more willing to accept pharmacogenetic testing if they are well informed about it.

Although pharmacogenetics (PGx) promises to optimize patient response to therapy, patients may be caught off guard if asked about “DNA testing to guide therapy.” Patients may even be inclined to skepticism. If so, they may be less willing to consent to tests or comply with treatment recommendations. Moreover, if they are making decisions not for themselves, but for their children, they could be even more reluctant to accept an unfamiliar course of action.

To explore these possibilities, researchers at Western University conducted a survey among parents and other adults—236 medical students representing those having greater educational exposure to PGx, 1,226 lay parents, and 105 lay people without children. A second survey was completed by 229 parents.

The study concluded that the acceptability of PGx testing, either for oneself or one’s child, seemed to depend on baseline PGx knowledge, but not on parenthood. The main concern for all respondents was the need for informed consent.

The results of the study were presented April 28 in Pediatrics, in an article entitled “Public Perceptions of Pharmacogenetics.” According to the study’s leader, Michael J. Rieder, M.D., Ph.D., professor of pediatrics and of physiology and pharmacology at Western University, the study confirmed what his team suspected: “Whether or not you’re a parent, your degree of acceptability of genetic testing was determined by your knowledge of it. That is to say—if you understand what the test is for, and the concept of gene-based drug dosing, you’re far more open to it, than if you don’t understand it.”

The study’s other findings included the following:

  • More acceptance for PGx when the disease was severe.
  • Strong desire/demand for separate consent for PGx testing.
  • More education about PGx needed in medical schools.
  • Acceptability of genetic testing didn’t differ whether for the parent or the child.

Dr. Rieder added PGx should take a lesson from pediatric oncology. According to Dr. Rieder, health care workers in that division do a good job in the way they frame the discussions around care, treatment, and consent: “When they have to make a diagnosis, they spend a lot of time explaining what tests they’re going to do, the risks, and what therapies are available. And they’re successful. Their patients comply with treatment, they get involved in studies, and they’re informed. And they want to know what’s going on.”


First Issue of Clinical OMICs Available Now

Wednesday, April 23, 2014

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

Clinical OMICs Issue 1


Defining a Molecular Dx Curriculum for Clinical Lab Scientists

Kevin Mayer

Wednesday, April 23, 2014

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To date, training programs in molecular diagnostics have been proliferating beyond anyone’s ability to define a curriculum. But at least one organization is trying to provide some guidance. This organization is the Association for Molecular Pathology (AMP). Because the AMP is home to all molecular diagnostics professionals, contends Elaine Lyon, Ph.D., the organization’s president, it “has a responsibility to help guide the training of future molecular technologists.”

To fulfill this responsibility, the AMP issued a set of recommendations that appeared April 22 in the Journal of Molecular Diagnostics, in a report entitled “Molecular Pathology Curriculum for Medical Laboratory Scientists.” The report’s authors, who represent the Medical Laboratory Scientist (MLS) Curriculum Task Force of the AMP Training and Education Committee, were fully aware of the unique challenges faced by educators, students, and clinical laboratories.

As indicated in the report, “Curriculum development is a challenge because educators must balance the requirements of accreditation, certification, and the needs of the job market. Educators in molecular diagnostics face another challenge in maintaining relevance of their programs with the rapidly changing technological advances in the field.”

While formulating its response to these challenges, the AMP solicited inputs from three key elements:

1. The National Accrediting Agency for Clinical Laboratory Sciences (NAACLS) guidelines for accreditation of molecular diagnostics programs.
2. Guidelines of several key certifying bodies for clinical laboratory scientists.
3. Feedback from current employers of molecular diagnostics scientists via a survey of AMP members.

All the stakeholders tended to focus on general education, not facility with specific laboratory platforms. Possibly this emphasis reflected the stakeholders’ recognition that different laboratories use a diverse variety of platforms, and even an individual laboratory may deploy new platforms as technology advances. In any event, the report indicated that educators “should encourage the development of fundamental skills in trainees, with the focus on understanding core concepts and skills that are generally universal across laboratories, such as DNA isolation, PCR-based methods, quality assurance, and critical thinking skills.”

Where the guidelines do become specific, however, relates to the academic levels of laboratory scientists who perform molecular diagnostic testing. “There are at least three major professional levels of laboratory scientist who perform molecular diagnostics testing: the generalist MLS/CLS, the bachelor’s-level laboratory scientist with specialized molecular training, and the master’s-level laboratory scientist with specialized molecular training,” said the report. “Individuals in each of these professional categories are expected to perform molecular diagnostic testing at different entry-level proficiencies.”

The AMP defines the different levels of proficiency across numerous variables, which range from nucleic acid chemistry to basic laboratory mathematics to familiarity with concepts of assay validation and assay development.

Up-and-coming molecular diagnostic laboratory scientists should complete an NAACLS-accredited training program, asserts the AMP, then become certified or licensed in their state of employment. According to the AMP, if its specific curriculum recommendations are adopted, tomorrow's medical laboratory scientists will be prepared for “the reality that molecular diagnostics are an integral and growing part of the clinical diagnostic laboratory.”


Lightweight Algorithms Sail through RNA Sequencing Data

Kevin Mayer

Monday, April 21, 2014

The Sailfish logo. [Carnegie Mellon University]

A flood of RNA sequencing (RNA-seq) data is already overwhelming existing systems for data analysis. And the waters are bound to keep rising, now that RNA-seq, the primary means of measuring gene expression, is increasingly seen as a tool not only for basic researchers, but also for medical practitioners.

Particularly challenging is the comparison of multiple RNA-seq datasets, including archived datasets, to detect changes in gene expression over time, or differences in gene expression that occur when disease strikes. Such comparisons, however valuable scientifically or clinically, are extremely time consuming, particularly if they depend on frequent reanalysis to capture fluctuations in gene activity.

To facilitate the analysis (and reanalysis) of RNA-seq datasets, computer scientists have been trying various ways to wring the as much performance as possible out of data-analysis platforms. And now, one group of computer scientists, representing researchers from Carnegie Mellon University and the University of Maryland, report that they have developed a new computational method that dramatically speeds up estimates of gene expression.

With the new method, dubbed Sailfish after the famously speedy fish, estimates of gene expression that previously took many hours can be completed in a few minutes, with accuracy that equals or exceeds previous methods. The researchers’ new method was presented online April 20 in the journal Nature Biotechnology, in an article entitled “Sailfish enables alignment-free isoform quantification from RNA-seq reads using lightweight algorithms.”

The article’s authors emphasised that gigantic repositories of RNA-seq data now exist, making it possible to re-analyze experiments in light of new discoveries. “But 15 hours a pop really starts to add up, particularly if you want to look at 100 experiments,” said Carl Kingsford, Ph.D., an associate professor in CMU's Lane Center for Computational Biology. “With Sailfish, we can give researchers everything they got from previous methods, but faster.”

The RNA-seq process results in short sequences of RNA, called “reads.” In previous methods, the RNA molecules from which they originated could be identified and measured only by painstakingly mapping these reads to their original positions in the larger molecules.

But the Carnegie Mellon and University of Maryland researchers realized that the time-consuming mapping step could be eliminated. Instead, they found they could allocate parts of the reads to different types of RNA molecules, much as if each read acted as several votes for one molecule or another.

In their article, the researchers explained how their approach worked in terms of k-mers, which refer to nucleotide sequences of length k. “A key technical contribution behind our approach is the observation that transcript coverage can be accurately estimated using counts of k-mers occurring in reads instead of alignments of reads,” the authors wrote.

“By working with k-mers, we can replace computationally intensive read mapping with the much faster and simpler process of k-mer counting,” the authors continued. “One can view the k-mer counting mechanism as a proportional assignment of a read to a set of potential loci, with the strength of the assignment varying with the number of k-mers in the read that match the locus.”

By avoiding the time-consuming step of read mapping, the authors reported, Sailfish is able to provide quantification estimates 20–30 times faster than many current methods without loss of accuracy.

The researcher’s numerical approach might not be as intuitive as a map to a biologist, but it makes perfect sense to a computer scientist, declared Dr. Kingsford, who added that the Sailfish method is more robust—better able to tolerate errors in the reads or differences between individuals’ genomes. These errors can prevent some reads from being mapped, he explained, but the Sailfish method can make use of all the RNA read “votes,” which improves the method’s accuracy.


A Chromosomal Rearrangement by Any Other Name

Kevin Mayer

Thursday, April 17, 2014

Source: © drizzd - Fotolia.com

The name of one thing or another, in isolation, may seem arbitrary, as poets and artists have suggested from time to time. Scientists, however, have a different perspective. They cannot accept, as a painter once declared, that the “precision of naming takes away from the uniqueness of seeing.” For scientists, names don’t necessarily exist in isolation. Rather, names may be elements in a system of names, a nomenclature.

Scientists agree on nomenclatures—which, admittedly, hold little or no intrinsic interest—because they ease communication and prevent confusion, which can otherwise settle over a subject like a fog. One such subject, cytogenetics, has dispelled fogginess for quite some time, thanks in part to the International System for Human Cytogenetic Nomenclature, which is the current official classification system used to describe structural chromosome rearrangements. While it has served admirably, this system is due for an update.

The current nomenclature evolved to systematize communications about chromosomal abnormalities at the microscopic level, which made sense because most observations were derived from the comparison of karyograms, or pictures of chromosomes. But now, with observations at the DNA level becoming increasingly common, researchers and clinicians alike are having difficulty communicating. They lack a clear consensus about how they should describe genetic abnormalities that occur at the DNA level when chromosomes swap, delete, or add parts. As a result, inconsistencies are creeping into research and clinical reports.

Determined to act before an already thickening fog can envelop cytogenetics is a team of researchers at Brigham and Women’s Hospital (BWH). It proposes a new classification system—Next-Gen Cytogenetic Nomenclature—that may standardize how structural chromosomal rearrangements are described.

The system was first presented online April 17 in The American Journal of Human Genetics, in an article entitled “Describing Sequencing Results of Structural Chromosome Rearrangements with a Suggested Next-Generation Cytogenetic Nomenclature.”

According to the article’s authors, advances in next-generation sequencing methods and results from BWH’s Developmental Genome Anatomy Project (DGAP) revealed an assortment of genes disrupted and dysregulated in human development in over 100 cases. Given the wide variety of chromosomal abnormalities, the researchers recognized that more accurate and full descriptions of structural chromosomal rearrangements were needed.

“Currently, most DNA sequencing reports only provide nucleotide numbers of the breakpoints in various formats based on the reference genome sequence alignment,” said lead study author Zehra Ordulu, M.D., BWH department of obstetrics, gynecology, and reproductive medicine. “But there are other important characteristics of the rearrangement—including reference genome identification, chromosome band level, direction of the sequence, homology, repeats, and nontemplated sequence—that are not described.”

The proposed system addresses these characteristics and builds upon the current classification system. In particular, the proposed system would incorporate an online tool called the BLA(S)T Output Sequence Tool of Nomenclature, or BOSToN. The tool works by aligning nucleotide sequences to reference human genome sequences. After processing the genetic information, the end result is the Next-Gen Cytogenetic Nomenclature that researchers and clinicians can then incorporate into their reports.

“BOSToN will reduce errors in sequence assessment and save time in generating nomenclature,” asserted senior study author Cynthia Morton, Ph.D., BWH director of cytogenetics, who added that accuracy and timeliness are “both of critical importance in the clinical setting.”

“As scientists we are moving the field of cytogenetics forward in the clinical space,” Dr. Morton concluded. “We will be able to define chromosomal abnormalities and report them in a way that is integral to molecular methods entering clinical practice.”


Clinical OMICs Launched

Wednesday, April 16, 2014

It is not a question of if molecular profiling—the gamut of omics technologies—will enter the clinic, or even when. Clinical omics is happening now. And so, questions about clinical omics are taking a more practical turn, particularly for those who have a professional interest in overseeing, or at least accommodating, omics’ transformation of medicine.

A new resource, one that focuses on the most clinically relevant information, is overdue. Already, clinicians are systematically evaluating the benefits of sequencing technologies, building data repositories, and tackling practicalities such as reimbursement and protocols for incidental findings. Moreover, even as single-gene effects are informing clinical decisions, system-level processes are being scrutinized for ways to distinguish between wellness and ill health. Multidimensional, computationally rich approaches represent the next wave of innovation, taking personalized medicine to the next level, while demanding more of practitioners, who in turn demand convenient, informative updates on the ever-changing state of clinical omics. As such, the time is ripe for this publication, Clinical OMICS.


Call to Action

Tuesday, April 15, 2014

Vural Özdemir, M.D., Ph.D., is editor-in-chief of OMICS: A Journal of Integrative Biology, published by Mary Ann Liebert, Inc. He is also an associate professor of human genetics at the council of higher education in Ankara, Turkey, and an independent scholar in science studies and advisor to the office of the president for international technology policy at Gaziantep University, also in Turkey.

Dr. Özdemir is one of the world’s leading scientific and policy advocates for moving OMICS discovery research to clinical practice and public health action. He has published extensively on OMICS biotech applications in medicine and public health, personalized healthcare, postgenomics diagnostics, and OMICS innovation policy, and he has supervised the publication of special issues of the OMICS journal focused on postgenomics fields such as vaccinomics, nutrigenomics, public health genomics, and theranostics.

Dr. Özdemir is especially supportive of the emerging discipline of nutrigenomics, which searches for the genetic factors that influence the body’s response to diet and explores how the bioactive constituents of food affect gene expression. He believes that in the future nutrigenomics may help guide the development of customized diets based on an individual’s genetic make-up.

In addition, he is one of the early proponents for the study of vaccinomics, which relies on the integrated use of multi-omics data intensive biotechnologies (e.g., genomics, proteomics, metabolomics) to understand individual and population differences in immune responses to vaccines. Vaccinomics, according to Dr. Özdemir, holds great promise for the design of safer and more effective vaccines and their targeted rational use via novel postgenomics diagnostics to prevent and combat infectious diseases. The discipline also points to interventions in chronic noncommunicable diseases such as cancer, diabetes, and obesity.


Roche Purchases Bolster the Firm’s Molecular Dx, Gene Regulation Capabilities

Friday, April 11, 2014

Source: © Kirsty Pargeter/Fotolia.com

In an effort to strengthen its molecular diagnostics offerings, Roche has just nabbed Massachusetts-based firm IQuum, a company that develops point-of-care products for molecular diagnostics. Roche will pay IQuum shareholders $275 million upfront and up to $175 million in product-related milestones. IQuum will be folded into Roche Molecular Diagnostics once the merger is complete.

With the acquisition, Roche is getting IQuum's Laboratory-in-a-tube (Liat™) System, which IQuum says allows healthcare workers to perform rapid molecular diagnostic testing in a point-of-care setting, along with the Liat Analyzer and Liat Influenza A/B Assay, the first test available for use on the system.

But, that's not Roche's only big purchase today: The Swiss firm also inked a deal with Spanish firm Oryzon Genomics to research, develop, and commercialize inhibitors of lysine-specific demethylase-1 (LSD1; KDM1A), an epigenetic modulator that regulates gene expression. Among the inhibitors that are part of the deal is Oryzon's lead molecule ORY-1001, which right now is in a Phase I/IIa trial for acute myeloid leukemia.

Per this deal, Roche is paying Oryzon $21 million upfront and for near-term milestones, plus potential milestone payments that could exceed $500 million across hematology, cancer, and nonmalignant indications. Roche will also pay royalties on sales that range up to mid-double digits.

A two-year collaborative research program between Oryzon and Roche’s Translational Clinical Research Center (TCRC) is also a part of the deal, the aim of which is to understand the potential of LSD1 inhibitors in oncology and hematology.

"Our TCRC in New York has been launched with a mandate to identify partnerships that drive innovation, providing an industry-leading conduit between sources of breakthrough science and the broader Roche organization," John Reed, Roche’s head of pharma research and early development, said in a statement. "This collaboration on LSD1 inhibition with Oryzon fulfills that mandate perfectly."


Using Genomics to Prevent Cancer

Friday, April 11, 2014

Genetic Alliance, in partnership with the Centers for Disease Control’s Office of Public Health Genomics, has released a set of videos to share information on the importance of Tier 1 genomic applications with all interested partners as well as state departments of public health. Early detection and intervention are key to reducing the negative effects of these conditions, and these videos are part of a larger effort to facilitate the development of programs that can save thousands of lives through screening and prevention of these three conditions.

Using Genomics to Prevent Cancer Now helps partners who are interested in addressing this important health challenge.  The video features Dr. Muin Khoury of CDC and Dr. Francis Collins, Director of the NIH; as well as other prominent public health and healthcare provider, payer, and patient leaders along with links to further information.


A $1,000 Proteome? Protein Sequencers Raise the Question

Kevin Mayer

Friday, April 11, 2014

Source: AlienForce - Fotolia.com

Development of better, cheaper, and more clinically relevant genomic analysis continues apace, but what about the proteome? If anything, the proteome—the full set of expressed proteins—would tell us more about wellness and ill health than the genome. True, genes constitute the foundation of life’s chemical hierarchy, but proteins (to mix metaphors) are where the rubber meets the road. Besides catalyzing the chemical reactions that sustain life, proteins are directly engaged in critical functions such as growth, differentiation, and repair; defense against pathogens; cellular housekeeping; and myriad structural duties.

So how hard could compiling a proteome be? After all, genome sequencing has become almost routine, and just 1.5% or so of the genome codes for proteins. Well, this is where things get tricky. While there are only about 25–25,000 human genes, scientists have already identified over 100,000 human proteins, and many, many more proteins no doubt remain unidentified. What’s more, the human proteome has millions of protein variants due to alternative RNA splicing and post-translational modification. And even that’s not all: It also appears that many so-called noncoding RNAs can actually give rise to physiologically relevant micropeptides.

If all that doesn’t sound daunting enough, consider this: Aberrant proteins that are indicative of disease or disease propensity are often present in extremely minute quantities. How could such proteins serve as biomarkers if they are so few and far between that they remain, essentially, invisible? Alas, no technology exists that could do for these proteins what the polymerase chain reaction (PCR) does for targeted regions of DNA. That is, no means exist to boost the concentrations of selected proteins and thereby enhance signal strengths.

Taking the measure of the proteome remains a huge challenge, but many researchers insist on trying. For example, a team of researchers at Arizona State University’s Biodesign Institute led by Stuart Lindsay, Ph.D., are refining a technique for single-molecule protein sequencing. The technique, which adapts technology that the team had used to sequence DNA, is known as recognition tunneling. It involves threading a peptide through a nanopore, an extremely tiny eyelet, which separates two electrodes that are coated with a layer of recognition molecules. When the protein is held between the electrodes, changes in the electron tunneling current between the electrodes is measured. Then, the current "signature" is analyzed to identify the amino acid. (Conceivably, this technique could be applied to peptides, amino acid by amino acid.)

The procedure is described in detail in a paper that appeared April 6 in Nature Nanotechnology, in a paper entitled “Single-molecule spectroscopy of amino acids and peptides by recognition tunneling.” According to this paper, signal analysis turned out to be fairly complex, requiring the services of a machine learning algorithm. This algorithm, called the Support Vector Machine, was used to train a computer to make sense of the signals that were emitted when the amino acids formed bonds in the tunnel junction and current flowed between the electrodes.

The algorithm—the same one used by the IBM computer Watson to defeat a human opponent in Jeopardy—helped the computer learn to discriminate between the different signals that could be emitted by the same molecule. For example, many molecules are able to bind with the tunnel junction in different ways. Also, as indicated in the paper, recognition tunneling let the researchers “identify D and L enantiomers, a methylated amino acid, isobaric isomers, and short peptides.”

The results of their work, reported the researchers, “suggest that direct electronic sequencing of single proteins could be possible by sequentially measuring the products of processive exopeptidase digestion, or by using a molecular motor to pull proteins through a tunnel junction integrated with a nanopore.”

“The ability of recognition tunneling to pinpoint abnormalities on a single molecule basis,” asserted Dr. Lindsay, “could be a complete game changer in proteomics.” Dr. Lindsay adds that the kind of work accomplished by his team—exploring innovative strategies for handling single molecules coupled with startling advances in computing power—may open up horizons that were inconceivable only a short time ago.

By showing that the kinds of tools that made the $1,000 genome feasible are applicable to proteome profiling, Dr. Lindsay’s team may even hearten those so bold to anticipate a $1,000 proteome. “Why not?” Dr. Lindsay asks. “People think it’s crazy, but the technical tools are there. And what will work for DNA sequencing will work for protein sequencing.”

While the tunneling measurements have until now been made using a complex laboratory instrument known as a scanning tunneling microscope, Dr. Lindsay and his colleagues are currently working on a solid-state device that may be capable of fast, cost-effective, and clinically applicable recognition tunneling of amino acids and other analytes. Eventual application of such solid-state devices in massively parallel systems could make clinical proteomics a practical reality.


Super Sequencing Predicts Toxicity of Superbug Strains

Friday, April 11, 2014

A highly toxic MRSA strain (top) and less toxic strain (bottom) cultured on a blood agar plate. [Dr. Massey/University of Bath]

As the cost and speed of genome sequencing decreases, the technique promises myriad clinical applications, including the sequencing of infecting organisms. With an infecting organism’s entire gene sequence in hand, a clinician could select an appropriate treatment—or even personalize it, maximizing the benefit for an individual patient who may, for example, be fighting a particularly virulent bacterial strain, perhaps even a strain of the dreaded MRSA, or methicillin-resistant Staphylococcus aureus.

In the case of MRSA, multiple lineages have developed, some more virulent than others. Since virulence depends, in part, on toxicity, or the bacterium’s ability to damage a host’s tissue, clinicians have been interested in finding ways to assess the toxicity of MRSA and other bacteria. To date, the standard approach used to assess MRSA’s toxicity has focused on a single or small number of genes and proteins. This approach, however, has had only mixed success. Toxicity, it turns out, is a complex trait, one that is encoded by many genetic loci.

To better grapple with MRSA’s toxicity, researchers at the University of Bath and the University of Exeter applied the technique of whole-genome sequencing, as they explained in an article they published April 9 in Genome Research. According to this article, which carries the title “Predicting the virulence of MRSA from its genome sequence,” the researchers used whole-genome sequences from 90 MRSA isolates to identify over 100 genetic loci that made an individual isolate either high or low toxicity. The researchers were surprised to find that isolates from the same ST239 clone varied hugely in toxicity.

Besides identifying a large number of loci, the researchers also uncovered a putative network of epistatically interacting loci that significantly associated with toxicity. “Despite this apparent complexity in toxicity regulation,” the authors wrote, “a predictive model based on a set of significant single nucleotide polymorphisms (SNPs) and insertion and deletions events (indels) showed a high degree of accuracy in predicting an isolate’s toxicity solely from the genetic signature at these sites.”

In short, the researchers identified a common genetic signature shared by all the highly toxic strains. By looking for this signature, they were able to predict which isolates were the most toxic and therefore would cause severe disease.

Lead author of the study, Ruth Massey, Ph.D., a senior lecturer at the University of Bath, remarked that in the future “it will become feasible to take a swab from a patient, sequence the genome of the bacterium causing the infection, and then use this to predict the toxicity of the infection.”

“Clinicians will then be able to tailor the treatment to the specific infection,” Dr. Massey added. “This technique can tell them which combination of antibiotics will be most effective, or tell them which drugs to administer to dampen the toxicity of the infection.”

Mario Recker, Ph.D., associate professor in applied mathematics at the University of Exeter and co-author of the paper, said the research could provide pivotal insight into the virulence of MRSA. “By using whole-genome sequences, we have been able to predict which would be most toxic and so therefore would be more likely to cause severe disease. Having identified these novel genetic loci will also shed more light upon the complex machinery regulating bacterial virulence.”


Bio-Rad Grows Droplet-Based DNA Sequencing Business with GnuBio Purchase

Friday, April 11, 2014

Source: Andrzej - Fotolia.com

Bio-Rad Laboratories said today it acquired GnuBIO, in a deal that expands the acquiring company’s droplet-based DNA sequencing technology offerings within its portfolio of clinical diagnostics products. The price was not disclosed.

GnuBIO says its namesake platform shortens the analysis timeframe for desktop DNA sequencing from days to hours by incorporating all of its functions—including target selection, DNA amplification, DNA sequencing, and analysis—into a platform with a single integrated workflow designed for the medical diagnostics and research markets.

"We believe GnuBIO's innovative DNA workflow is well-suited for the clinical diagnostics sequencing market and will leverage Bio-Rad's leadership role in the area of droplet digital PCR,” Norman Schwartz, Bio-Rad’s president and CEO, said in a statement.

The deal is the second acquisition of a droplet digital PCR system developer in the past 2-1/2 years for Bio-Rad, which specializes in tools and services to the life science research and clinical diagnostics markets. In October 2011, Bio-Rad spent $162 million to acquire QuantaLife, whose product line included the Droplet Digital™ (ddPCR™) system. Bio-Rad says the current second-generation version of that system, the QX200 Droplet Digital PCR system, provides absolute quantification of target DNA or RNA molecules for EvaGreen or probe-based digital PCR applications.

GnuBIO’s platform uses microfluidic and emulsion technology to perform complex, multiplexed reactions in droplets. The technology is scalable, allowing for interrogation of single genes, gene panels or whole genomes.

Headquartered in Cambridge, MA, privately held GnuBIO commercializes technology developed in the laboratory of David Weitz, Mallinckrodt Professor of Physics & Applied Physics at Harvard University. The National Science Foundation (NSF) partially funded Weitz’ lab to develop the GnuBIO prototype, which it shipped as an early-access instrument to the Montreal Heart Institute in 2011. A year later, GnuBIO unveiled the platform at the Association of Molecular Pathology (AMP) 2012 Annual Meeting in Long Beach, CA.

The platform began commercial shipment to customer sites last year, with a $50,000 price and the promise of delivering an analyzed sequence of the gene panel, including variant calls and quality scores, in 3.5 hours.

In 2012, GnuBIO completed a $10 million Series B round of equity financing from a group of private investors, which include existing Series A shareholders, and won a $4.5 million grant from NIH’s National Human Genome Research Institute.


Archive



CLINICAL OMICS ISSUE 11: October 8, 2014

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CLINICAL OMICS ISSUE 10: September 24, 2014

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CLINICAL OMICS ISSUE 9: September 10, 2014

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CLINICAL OMICS ISSUE 8: August 13, 2014

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CLINICAL OMICS ISSUE 7: JULY 16, 2014

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Clinical OMICS Issue 6: June 26, 2014

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Clinical OMICs Issue 5: June 12, 2014

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CLINICAL OMICS ISSUE 4: MAY 29, 2014

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CLINICAL OMICS ISSUE 3: MAY 15, 2014

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Clinical OMICs Issue 2: April 30, 2014

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Clinical OMICs First Issue: April 23, 2014

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Cancer Personalized Medicine: What You Need to Know

In this GEN Market & Tech Analysis report we examine the landscape of cancer personalized medicine based on the results of bottom-up market analyses, which pinpoint the current status and trajectory of cancer personalized medicine.

Highlights of this report:

  • Cancer personalized medicine is the major driver moving the entity of personalized medicine and patient-disease management forward.
  • 70% of the total efforts in the personalized medicine space are focused on the various cancer segments taken together.
  • The impact of microRNAs, epigenetics, and other novel biomarker classes on the cancer personalized medicine space is small currently—indeed the majority of biomarkers are gene- and protein expression-based.
  • The impact of companion diagnostics and tailored therapeutics development is expected to expand the reach of personalized medicine beyond cancer into other disease classes.
  • The collision of NGS into cancer personalized medicine has begun.
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The approval by the FDA of Illumina’s MiSeqDx platform is a key driver of the translation of NGS toward the clinic. [© taraki - Fotolia.com]

Next-Gen Sequencing Update

We provide an update of the trajectory of the migration of next-generation sequencing (NGS) from the research space toward clinical application and clinical impact in this GEN report as part of our continuing coverage of the evolution of the NGS industry landscape.

Highlights of this report:

  • There are defined research offerings from several vendors for NGS front-end sample processing and preparation.
  • Many of these kit-formatted products are available and are designed for research use (RUO).
  • There is a defined clinical translation of NGS that is taking place, and one of the key drivers of this translation toward the clinic is the approval of the Illumina MiSeqDx platform by the FDA.
  • Indeed today there are a number of LDTs deploying NGS with specific gene panels—primarily focusing on oncology—but expanding out into other disease classes also.
  • The development of ecosystems of researchers developing NGS-based applications will propel this translation of NGS from research to clinic.
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Elaine R. Mardis, Ph.D. is one of the speakers.

Translating Next-Gen Sequencing from the Lab to the Clinic: Challenges and Solutions

The confluence of next-generation sequencing technologies, computational analysis of the data, and the use of targeted therapy in cancer care raises a “perfect storm” for revolutionizing the clinic. Sequencing experts, bioinformaticists, and clinicians agree that the challenges of translating the vast amounts of data from next-generation sequencing into a resource that can be easily and effectively incorporated into clinical and research programs are significant.

In this webinar, our presenters will cover several approaches aimed at streamlining the application of genomics data to clinical and personalized medicine. David Smith of the Mayo Clinic will describe analytical/informatics challenges, focusing on the Clinic’s approaches to presenting data generated from small gene panel, whole exome, whole genome, or whole transcriptome sequencing into a digestible form for clinicians.

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About

Clinical OMICs, a digital publication brought to you by the publishers of GEN, aims to be a go-to resource for clinicians interested in the transfer of OMICs technologies into the clinic. The publication will provide a roadmap that readers can follow in their quest to improve patient diagnosis and treatment.