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

Clinical OMICs Volume 2, Issue No. 3

News & Perspectives

Thursday, March 26, 2015

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Ten biopharma companies have joined together to create the Genomics Expert Network for Enterprises (GENE) Consortium, which will oversee a year-long trial designed to integrate industry expertise into the 100,000 Genomes Project—the U.K.’s effort to catapult itself to global leadership in genetic research into cancer and rare diseases.

Through the GENE Consortium, the companies will work to discover how best to collaborate with clinicians and researchers in studying a selection of whole genome sequences across cancer and rare diseases. The consortium’s work is intended to accelerate the development of new diagnostics and treatments for patients, said Genomics England, the entity created by the U.K. Department of Health to run the 100,000 Genomes Project.

The GENE Consortium’s 10 companies are: AbbVie, Alexion Pharmaceuticals, AstraZeneca, Biogen (which changed its name from Biogen Idec as of Monday), Dimension Therapeutics, GlaxoSmithKline, Helomics, Roche, Takeda, and UCB—whose participation is subject to contract negotiation and signature, Genomics England added.

“We are particularly looking forward to contributing our expertise in understanding the role of biomarkers and personalised healthcare in the development of targeted medicines for patients,” Mene Pangalos, Ph.D., AstraZeneca’s evp of innovative medicines and early development, said in a statement.

Helomics said in a company statement it will provide its PCAPTM tumor profiling technology and diagnostics-focused expertise to the consortium. The company said its goal was to identify new biomarkers that could be used to develop more advanced cancer diagnostic tests and ultimately lead to new levels of personalized medicine.

Genomics England also disclosed the areas where leading clinicians and scientists across the U.K. will explore within Genomics England’s Clinical Interpretation Partnership (GeCIP), formed to identify scientific findings and medical discoveries from the 100,000 Genomes dataset.

As part of GeCIP, more than 28 teams or “domains” will be established for clinical and research experts in which to work. These include rare disease—a category it said will include cardiovascular, neurological, paediatrics domains—as well as cancers; pan-cancer analysis across many cancers; functional effects on gene expression, proteins and life-long DNA changes; electronic health records research; ethics, law and social science; health economics; validation and feedback.

The 28 were selected from 88 applications to join GeCIP made by more than 2,000 researchers, clinicians, analysts, and trainees following a call to the research community in November 2014, Genomics England said.

GeCIP—whose members will include academic institutions, the National Health Service (NHS) Genomic Medicine Centres and industry—will ultimately bring together more than 4,000 U.K. clinicians and scientists, as well as over 500 international collaborators specializing in genomic medicine, Professor Mark Caulfield, M.D., FMedSci, chief scientist for Genomics England, said in a statement.

“We hope that this unique collaboration will lead to earlier and more precise diagnoses for patients and, working with companies, will pave the way for new, more targeted therapies and treatments,” Professor Caulfield added.

According to Genomics England, nearly 3,000 genomes have been sequenced to date as part of the 100,000 Genomes Project, launched in late 2012 by U.K. Prime Minister David Cameron with the goal of mapping 100,000 human genomes from NHS patients by 2017. The project is focusing on patients with rare diseases, and their families, as well as patients with common cancers.

Last year, Illumina, the U.K., and the Wellcome Trust agreed to spend £311 million (nearly $464 million) over four years on the project, which relies on a public-private partnership formed between sequencing giant Illumina and Genomics England.

Tuesday, March 24, 2015

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IntegraGen will oversee high-throughput sequencing activities for the National Reference Center (NRC) and microbiological collections at the Institut Pasteur.

The partnership’s primary objective, according to IntegraGen, is to increase access to next-generation sequencing technologies for the 15 NRCs and the institute’s microbiology collection. The partnership also aims to establish reference tools for the typing of bacterial, viral, and fungal strains.

Additionally, IntegraGen said, it will develop management software tailored to the Institut Pasteur’s internal needs.

“This agreement also represents an opportunity for us to expand our genomics business and to continue to grow our revenue,” IntegraGen CEO Bernard Courtieu said in a statement.

The publicly traded company finished last year with revenue of €6 million (nearly $6.6 million), an increase of 12% over 2013. In addition to identifying biomarkers and commercializing molecular diagnostic tests for autism and oncology, IntegraGen provides genomic services to academic researchers and life sciences companies.

Last month, the company announced the launch of GeCo, a genomic consulting service directed toward academic and corporate genomics researchers.

“Having access to IntegraGen's know-how in high-throughput sequencing is a major asset to reinforce our mobilization abilities and to ensure our mission for public health at the highest level,” added professor Christian Bréchot, M.D., Ph.D., general manager of the Institut Pasteur.

Tuesday, March 24, 2015

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Dako, an Agilent Technologies company specializing in providing cancer diagnostics, said today it has again expanded a three-year-old collaboration with Amgen focused on companion diagnostics.

The value of the expanded collaboration and other financial terms were not disclosed. Dako said the expanded “multi-year” collaboration will allow both companies to benefit from knowledge-sharing within drug-diagnostic R&D, particularly in relation to companion diagnostic products.

“Together we will continue our work in the development of high-quality companion diagnostic products to enable physicians and pathologists to identify cancer patients who are more likely to respond to a specific therapy,” Jacob Thaysen, president of Agilent's Diagnostics and Genomics Group, said in a statement.

Dako and Amgen launched their collaboration in January 2012, when they agreed to develop a diagnostic test for an undisclosed Amgen drug candidate that Dako said was “targeted for a rare and deadly cancer.” A month later, the companies began a second collaboration to develop pharmDx™ for an undisclosed Amgen cancer drug candidate in clinical development. Dako was acquired by Agilent in May 2012 for $2.2 billion.

Amgen’s online pipeline, last updated February 12,  lists six Phase I compounds with cancer indications, as well as three Phase II and five Phase III compounds.

Last year the companies expanded their partnership, as Dako initiated a new project with Amgen to develop a molecular diagnostic test using Dako’s IQFISH hybridization buffer.

The IQFISH hybridization buffer, introduced by Dako in 2012, is designed to slash diagnostic test turnaround time from 17 hours to just 3.5 hours. It enables pathology labs—for the first time—to run DNA-based hybridization assays quickly, with distinct and higher fluorescent signal intensity compared to traditional FISH assays.

Amgen is among several biopharma giants with which Dako has teamed up. Last year, Dako launched a collaboration with Merck & Co. to develop a companion diagnostic test designed to analyze the potential tumor biomarker PD-L1, as part of the clinical development program for Merck & Co.’s investigational anti-PD-1 antibody under study as a potential cancer treatment.

In the two years preceding the Amgen deal, Dako inked agreements with AstraZeneca, Bristol-Myers Squibb, and Roche’s Genentech subsidiary.

Tuesday, March 17, 2015

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Qiagen acquired AdnaGen’s circulating tumor cell (CTC) enrichment technology to boost its capabilities in liquid biopsies. Separately, the company formed a partnership with Tokai Pharmaceuticals to combine its new CTC technology with a molecular assay to co-develop and commercialize a companion diagnostic for Tokai’s galeterone, which is in late-stage clinical trials for treatment of castration-resistant prostate cancer (CRPC). The noninvasive test will determine the expression of the AR-V7 biomarker, which in recent studies has demonstrated potential utility to guide therapy choice in CRPC patients, according to Qiagen officials.

“Following the success of the first-ever regulated companion diagnostic for solid tumors based on molecular biomarkers from a liquid biopsy in Europe, we are expanding our portfolio of highly accurate tests that analyze samples of body fluids that are noninvasive and more accessible than traditional tissue biopsies,” said Peer M. Schatz, CEO of Qiagen. “Our partnership with Tokai Pharmaceuticals, one of the collaborations which we are pursuing with pharma in this area, is expected to result in a liquid biopsy, CTC-based companion diagnostic, with potential to enhance outcomes for prostate cancer patients.”

AdnaGen’s CTC method relies on magnetic particles in an antibody mixture that isolates and purifies mRNA for analysis using RT-PCR. The test for Tokai will be developed by Qiagen Manchester, the global center for the development and regulatory approval of Qiagen’s molecular diagnostic applications.

Friday, March 13, 2015

Richard Scheller, Ph.D., is the new CSO and head of therapeutics at 23andMe.

Less than a month after winning its first FDA authorization, 23andMe is expanding beyond direct-to-consumer genetic testing by creating a new therapeutics group, and appointing Genentech’s recently retired evp of research and early development to lead the new unit.

Richard Scheller, Ph.D., has been named 23andMe’s CSO and head of therapeutics, effective at the beginning of next month. At the new 23andMe Therapeutics, Dr. Scheller will be charged with building a dedicated R&D team that will apply human genetic data toward new therapies for both common and rare diseases.

23andMe said it will link the work of the new therapeutics group with its research platform, which the company says includes the world's largest consented, re-contactable database. That database includes almost 900,000 customers who have contributed more than 250 million data points of information. Over 80% of customers chose to opt-in to research and answer questions, according to 23andMe.

“The same way we are transforming the way people access and understand their genomes, we hope to transform the way we discover and develop novel therapies. By starting with genetic information and understanding the basics of disease, we hope we can make discoveries that will have a meaningful impact on society,” 23andMe CEO and co-founder Anne Wojcicki said today in a post on the company’s blog.

“Our mission is to help people access, understand and benefit from the human genome. With Dr. Scheller joining the team, we believe we will be putting our best efforts into helping customers and society benefit from the human genome,” Wojcicki added. “We believe we have the potential to be the source of new discoveries that transform the health and lives of our friends and family.”

23andMe’s hiring of Dr. Scheller comes some two months after the company launched separate collaborations with a pair of drug developers. On January 12, 23andMe said it gave access to its research platform to Pfizer under a collaboration that will include genome-wide association studies, surveys, and clinical trial recruitment. The partners agreed to undertake a longitudinal study designed to better understand the genetics of lupus by enrolling and genotyping 5,000 people into a new lupus research community. That effort will include integration of medical records, targeted bio-sampling along with genetic information for all participants.

Six days earlier on January 6, 23andMe joined with Genentech in a partnership to generate whole genome sequencing data for about 3,000 people in 23andMe’s Parkinson’s disease community. The company said the multiyear collaboration—whose value has not been disclosed but according to one report was worth $60 million—was intended to identify new therapeutic targets for treating Parkinson’s disease.

Dr. Scheller retired in December 2014 from Genentech, a Roche subsidiary, after 14 years with the company—the last six as evp of research and early development. In that position, he led the company's research strategy, drug discovery, business development, and early drug development activities through proof-of-concept in the clinic. Dr. Scheller also oversaw Genentech’s basic research around oncology, immunology, neuroscience, and infectious disease.

Dr. Scheller served on the faculty of Stanford University for 19 years as a professor in the department of biological sciences and the department of molecular and cellular physiology and was an investigator at the Howard Hughes Medical Institute of Stanford University Medical Center. Since 2004, Dr. Scheller has also served as an adjunct professor in the department of biochemistry and biophysics at the University of California, San Francisco. He has published more than 280 research studies.

For his work elucidating the molecular mechanisms governing neurotransmitter release, Dr. Scheller has received several awards—including the 2014 California Institute of Technology's Caltech Distinguished Alumni Award, and the Albert Lasker Basic Medical Research Award a year earlier. Dr. Scheller was awarded his Ph.D. in chemistry from Caltech, and completed postdoctoral fellowships at the school’s division of biology, as well as at Columbia University’s College of Physicians and Surgeons, where he specialized in molecular neurobiology.

Friday, March 13, 2015

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Tute Genomics said today a company database containing 8.5 billion annotations of genetic variants will be made publicly accessible through Google Genomics, through a partnership with Google as well as Xiaoming Liu, Ph.D., and his team at the University of Texas, Houston Health Science Center’s Human Genetics Center.

According to its main page on Google Genomics, the Tute Genomics Annotation database consists of a curated collection of functional annotations for all possible single nucleotide variants (SNVs) in the human genome (hg19 build).

Data sources include clinical annotations from the National Center for Biotechnology Information’s ClinVar database, and the genome-wide association studies (GWAS) catalog; allele frequencies from the 1000 Genomes Project and National Heart, Lung, and Blood Institute Exome Sequencing Project (NHLBI-ESP) 6500 exomes.

Additional data sources include the Exome Aggregation Consortium 60,000 samples gene and transcript model annotations, such as amino acid and protein substitutions and the functional consequence of exonic variants. Additionally, the database includes conservation and evolutionary scores from tools like SIFT, PolyPhen2, PhyloP, MutationTaster, MutationAssessor, FATHMM, MetaLR, and MetaSVM.

Finally, the database contains Tute-developed scoring system to predict whether a SNP or indel is likely to be associated with Mendelian phenotypes. According to Tute Genomics, the clinical genome interpretation platform is designed to assist researchers in identifying disease genes and biomarkers, as well as assist clinicians/labs in performing genetic diagnosis and personalized therapeutics. Tute draws on expertise that developed the genome annotation and interpretation software ANNOVAR.

“The time is coming when genome sequencing will be part of routine clinical care, and open access to genetic variant databases is a necessary step in order to accelerate progress towards precision medicine,” Tute Genomics CEO Reid Robison, M.D., M.B.A., said in a statement.

Tuesday, March 10, 2015

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Illumina said today it launched a collaboration with Merck Serono—the biopharma unit of Merck KGaA—intended to develop a universal next-generation sequencing (NGS)-based oncology diagnostic. The value of the collaboration was not disclosed.

While saying it would continue pursuing separate collaborations announced in August 2014 with AstraZeneca, Johnson & Johnson’s Janssen Biotech, and Sanofi, Illumina said it will also work with Merck Serono to create a universal test system for clinical trials of targeted cancer therapies, with the goal of creating a more comprehensive tool for precision medicine.

Illumina said it is working with Merck Serono to develop assays that detect and measure multiple variants simultaneously to support clinical trials. The collaboration toward the universal cancer test will include test development, worldwide regulatory approvals, and global commercialization.

“This agreement is another step forward in realizing the promise of precision medicine," Illumina CMO Richard Klausner, M.D., said in a statement. He cited President Obama’s proposed $270 million Personalized Medicine Initiative, which has called in part for expanding genetically-based clinical trials as a key approach for developing better treatments for cancer.

Added Susan Herbert, Head of Global Business Development at Merck Serono: "Our collaboration with Illumina around next-generation sequencing will enable us to perform genome studies at a pace unheard of a few years ago, and could lead to the development of several diagnostics.”

In detailing its efforts toward a Universal Oncology Test System last year, Illumina articulated four objectives:

• Standardize: Enable standardization of a multiplexed platform for evaluating relevant genes.
• Streamline: Optimize the introduction of new biomarkers by using a standardized system.
• Decentralize: Deliver a universal platform for decentralized routine testing, enabling rapid commercial access.
• Collaborate: Facilitate combination trials within and across pharmaceutical companies.

“The benefits of this NGS-based tumor assessment assay will be numerous. For pharmaceutical companies, it will streamline the validation of clinically relevant variants, the development of new cancer drugs, and the implementation of these new therapies into clinical treatment regimens,” Illumina said in a whitepaper published in November 2014 and available on its website.

Illumina added that it continues to collaborate with leaders of the Actionable Genome Consortium to set standards for NGS-based assays in routine clinical oncology practice, as well as to define regulatory frameworks to enable widespread use of NGS.

Illumina co-formed the consortium in September 2014 with four cancer research institutes—Dana-Farber Cancer Institute, Fred Hutchinson Cancer Research Center, MD Anderson Cancer Center, and Memorial Sloan Kettering Cancer Center.

Friday, March 06, 2015

As with most healthcare decision, patients cannot rely on the Internet and oncology providers need to guide patients as make decisions about personalized cancer medicine. [© Alexander Raths/Fotolia.com]

Researchers from the Dana-Farber Cancer Institute report that websites that market personalized cancer care services often overemphasize their stated benefits and downplay their limitations. Many sites also offer genetic tests whose value for guiding cancer treatment has not been shown to be clinically useful, according to the team’s study (“Marketing of Personalized Cancer Care on the Web: an Analysis of Internet Websites”) in the Journal of the National Cancer Institute.

"Internet marketing may be detrimental if it endorses products of unproven benefit," write the investigators.

Internet marketing of cancer-related gene tests is unregulated so there is wide variation in how these services are presented, posing a challenge for consumers and their physicians, notes Stacy Gray, M.D., a medical oncologist and investigator at the Dana-Farber Center for Outcome and Policy Research and first author of the paper that analyzes 55 websites marketing the services.

"We wanted to see if consumers are getting a balanced picture of benefits and limitations of these services," says Dr. Gray. "We found a lot of variation. Some of the information is good, but all of it needs to be looked at critically by consumers and health care providers."

The study found that "in general, the benefits of these personalized cancer products are reported much more frequently than are the limitations," continued Dr. Gray. In addition, 88% of the websites offered one or more "nonstandard" tests that lacked evidence of clear clinical utility in routine oncology practice.

The scientists analyzed personalized or precision cancer medicine (PCM) products and services marketed by private companies, academic medical centers, physicians, research institutes, and other organizations. PCM was defined by the authors as "...products or services that could be used to tailor, personalize, or individualize care based on genomic or tumor-derived data." PCM often refers to testing DNA from samples of a patient's tumor to detect mutations or other genetic abnormalities. The results may help physicians predict how the disease will behave and select a drug or drugs targeted to the particular mutations found in the cancer. Such targeted agents may be more effective and cause fewer adverse side effects than standard chemotherapy.

These somatic tests look at the genetic characteristic of the tumor itself. Germline testing analyzes the patient's personal genome  and may turn up altered genes in a healthy person that raise his or her risk of developing cancer.

A majority of the Internet sites (58%) offered somatic testing, and 20% marketed germline testing, the study found. In addition, 44% of sites offered some form of personalized cancer care.
The report cited examples of marketing claims such as:

"Reduce trial and error at the prescription pad. Genetic testing is a tool for better patient care, greater accuracy, lower costs, enhanced care-that is our promise."
Using the marketer's "enhanced treatment options, our patients experienced a greater life expectancy, often with less side effects than standard treatment." A late-stage pancreatic cancer patient's life "was extended five years by (our product)-guided treatment."
"Our laboratory analyzes your tumor's response to 8-16 drugs and combinations to identify which treatments will work best to kill your cancer."
Claims and other information posted on Internet sites are not subject to regulation by agencies such as the FDA or the Federal Trade Commission. More recently, the FDA has said it intends to begin regulating genomic testing more broadly.

Even if regulation of the websites becomes a reality, the researchers said, "Oncology providers will need to guide patients as they navigate decisions about personalized cancer medicine."

Jeffrey S. Buguliskis, Ph.D.

Sunday, March 01, 2015

Sequencing of RNA molecules, like the one pictured above, is a powerful laboratory discovery tool that has the potential to play a major role in clinical diagnostics. [Shutterstock/©petarg]

Advances in genomics over the past several years have had a profound impact on our grasp of molecular biology and genetics. In the laboratory, next-generation sequencing (NGS) has been applied to identifying novel genomes for an array of organisms, DNA resequencing, transcriptome sequencing, and epigenetics. Within clinical settings, NGS is beginning to cut its teeth and is being rapidly embraced as an invaluable diagnostic tool. Specifically, the ability to interpret the genetic mechanisms that underlie variations in human gene expression through the direct analysis of the transcriptome makes RNA sequencing (RNA-Seq) an attractive method to clinical diagnosticians. “RNA-Seq provides a very specific and sensitive genomic signature that can be useful in many clinical situations,” said Gary Schroth, Ph.D., distinguished scientist at Illumina.

RNA-Seq examines the dynamic nature of the cell’s transcriptome, the portion of genome that is actively transcribed into RNA molecules. While DNA remains relatively unchanged throughout an individual’s lifespan, RNA, in the form of transcriptional elements, can vary dramatically due to influences on epigenetic regulators, alternative spliced variants, or post-transcriptional modifications.

For the rest of the story, click here.

Sunday, March 01, 2015

More than 100,000 health and wellness mobile apps are now available, a 2014 report shows. [© alexey_boldin/Fotolia]

As mobile technology has become more powerful and ubiquitous, it was only logical to assume that health and medical apps reaching directly to the consumer could significantly change how healthcare is delivered. From applications that help patients self-monitor their diet to exercise and wellness apps, the public’s appetite for taking greater control of their health via their tablets and smartphones continues to grow. With more than 100,000 apps now available, a 2014 report by research firm Research2Guidance projects the mobile health app market will have produced $26 billion in revenue by the end of 2017, up from only a few billion dollars to date.

And while this consumer health revolution is plain for all to see, a similar revolution, lagging by perhaps only a few years, is picking up steam in the medical imaging and diagnostic field. Leveraging both the improved imaging capabilities of smartphones and their increased computing power, new screening and diagnostic tools that target cancer, kidney disease, and influenza, among a host of others, are showing significant promise in moving the diagnostic lab to remote locations and, in the process, significantly improving the health of the underserved.

For the rest of the story, click here.

Patricia Fitzpatrick Dimond, Ph.D.

Sunday, March 01, 2015

Most cases of colorectal cancer evade early detection, with about 50% of patients being diagnosed at advanced tumor stages. [© adrenalinapura /Fotolia]

More than 1.2 million new cases of colorectal cancer (CRC) occur glob- ally each year, resulting in about 600,000 deaths. CRC remains the third most commonly diagnosed cancer in both men and women in the United States; estimated new cases in 2015 will reach 132,700.

Unfortunately, the majority of CRC cases continue to elude early detection. About 50% of CRC patients are diagnosed at advanced tumor stages. Such patients have poor prognoses. Earlier diagnoses, and better prognoses, may be attained by means of early screening for CRC. Implementing such screening has become one of the greatest public health challenges over the last 50 years.

A means of reliably predicting gene expression profiles (GEPs) for those who will develop CRC has proven hard to develop. And questions about the ultimate clinical utility of predictive tests for Stage II patients who require chemotherapy remain, even as companies continue to introduce new tests.

For the rest of the story, click here.

Emil Salazar

Sunday, March 01, 2015

Prenatal testing offers technologies like sequencing, microarrays, and mass spectrometry, pointing to opportunities for growth in clinical diagnostics. [© Photographee.eu/Fotolia]

Family planning and coordination of care for a child born with health conditions are significant concerns for the in vitro diagnostics (IVD) community, which is increasingly involved in the prenatal testing market. While ethical con- siderations will arise with further market development, prenatal, postnatal, and maternal testing are viable, prom- ising cytogenetic screening methods that have seen ready acceptance from many insurers in at-risk populations where the prevalence of genetic disorders (especially chromosomal) justify coverage.

Prenatal cytogenetic testing represents an important source of clinical market growth for technologies such as sequencing, microarrays, biomarker immmunoassays, and mass spectrometry. Kalorama Information has reported extensively on prenatal testing markets for more than a decade, but recently there’s been an increase in activity, as revealed in our latest study of the women’s health diag- nostics markets.

For the rest of the story, click here.

Tim Durfee, Dan Nash, Ken Dullea, Jacqueline Carville, Marjorie Beggs, Jon Wilson, Chris Larsen, and Frederick R. Blattner

Sunday, March 01, 2015


As next-generation sequencing (NGS) makes genetic testing for a wide range of human diseases increasingly commonplace, facile methods for validating the efficacy of those tests are essential. Federal regulatory standards embodied in the Clinical Laboratory Improvement Amendments (CLIA), for instance, are designed to ensure that these tests reliably achieve certain performance specifications in terms of accuracy, precision, and analytical sensitivity and specificity.

To facilitate the test validation process, the National Institute of Standards and Technology (NIST) through the Genome in a Bottle Consortium (GIAB) developed a highly curated set of genome-wide reference materials for the HapMap/1000 Genomes CEU female, NA12878. These materials include BED and VCF files of high confidence sequence regions and variant calls, respectively. NA12878 genomic DNA and a cell line are available (Coriell Institute) providing laboratories with an internal control for their processing and analysis pipeline.

Comparing testing results to the GIAB call sets allows establishment of both the analytical performance for regulatory certification as well as the appropriate assembly thresholds to apply when considering potential variants in clinical samples.

For the rest of the story, click here.

Thursday, February 26, 2015

Genomic rearrangements may result in stable, locally rearranged, scattered, or unstable mutational landscapes in pancreatic cancer. [© Mopic/Fotolia]

Genomics meets gene tectonics in a pancreatic cancer study that describes large-scale genomic rearrangements that can be likened to geological events. In pancreatic cancer, large slabs of DNA can slide from one genomic region to another, changing the genomic landscape. While DNA fault lines and ridges have been exposed by whole exome analysis, the broader picture is emerging only now, with the application of whole genome analysis.

With the benefit of the whole genome perspective, which takes in the whole genome, not just the genome’s protein-coding sequences, four kinds of genomic rearrangement have been uncovered—“stable,” “locally rearranged,” “scattered,” and “unstable.” These four pancreatic cancer types roughly correspond to different degrees of genetic upheaval and account for the frequency, location, and types of DNA redisposition. For example, genes can be inverted, deleted, or multiplied. Also, genes can sustain damage, much like landforms can be scarred near geologic fault lines.

These findings appeared February 25 in Nature, in an article entitled, “Whole genomes redefine the mutational landscape of pancreatic cancer.” Besides recognizing distinct forms of pancreatic cancer, the article emphasizes that the newly found categories could be used to improve treatments for the disease. In the case of “unstable” genomes, treatment prospects seemed especially promising.

“We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs),” wrote the authors. “Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A, and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2).”

Besides pointing out four distinct pancreatic cancer subtypes, the authors noted that DNA rearrangements caused genetic chaos, with genes deleted, wrongly switched on and off, or entirely new versions created. Some of the genetic faults, however, are may be treatable with existing drugs. According to the authors, potentially druggable oncogenes include ERBB2, MET, FGFR1, CDK6, PIK3R3, and PIK3CA.

The study’s authors, which included scientists from Cancer Research UK and the Garvin Institute of Medical Research, also suggested certain pancreatic cancer patients could benefit from platinum-based drugs.

“Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2, or PALB2) and a mutational signature of DNA damage repair deficiency,” they reported. “Of eight patients who received platinum therapy, four of five individuals with these measures of defective DNA maintenance responded.”

The study’s co-lead, Professor Andrew Biankin, affiliated with both Cancer Research UK and Garvin, and currently at the University of Glasgow, indicated that being able to identify which patients would benefit from platinum-based treatments would be a “game-changing moment, potentially improving survival for a group of patients.” More generally, Professor Biankin added, “Our crucial study sheds light on how the chaotic chromosomal rearrangements cause a huge range of genetic faults that are behind the disease and provide opportunities for more personalized pancreatic cancer treatment.”

Wednesday, February 25, 2015

Source: © rob3000/Fotolia

Selah Genomics, a subsidiary of EKF Diagnostics, entered an 18 month collaboration with Greenville Health System (GHS), DecisionQ, and Becton Dickinson and Company (BD). The goal of the alliance is to unite clinical annotations with next-generation sequencing (NGS) technology and artificial intelligence-based algorithms in hope of improving clinical decision making for the treatment of colon cancer, according to the organizations.

Selah will utilize its PrecisionPath™ NGS technology to determine the genetic profiles of tumor samples provided by GHS’ Institute for Translational Oncology Research. The company said the samples, from colon cancer patients with known outcomes, will be provided with full clinical annotation. DecisionQ will employ its machine-learning platform to integrate genetic profile data with clinical annotations to produce a model of a clinical decision support tool. Funding for the research project is being provided in part by BD in return for the first opportunity to license the technology if the collaboration is successful. A clinical trial is planned to validate the research and affirm the effectiveness of the new system. After proving the value for colon cancer, EKF and Selah said they plan to continue to evaluate similar models on other sites of origin.

“This initial collaboration will demonstrate the power of a new generation of personalized medicine decision support tools for oncologists, starting with a particular focus on empowering oncologists treating colon cancer patients in the community-based setting,” said Michael Bolick, CEO, Selah Genomics. “Leveraging particular contributions from each of our partners, we have a unique opportunity to fast track our development timelines across an array of targets.”

U.K. based EKF Diagnostics bought Selah Genomics in April 2014 as part of a deal worth up to $75 million. Selah has a history of collaborating with GHS in oncology research. Three years ago, the company established a lab at GHS’ Institute for Translational Oncology Research to implement PrecisionPath in a clinical setting.

Friday, February 20, 2015

The FDA has granted 23andMe authority for marketing a direct-to-consumer genetic test, nearly a year and a half after forcing the company to stop selling its Saliva Collection Kit and Personal Genome Service® (PGS), and submit to agency review of its test as a medical device.

23andMe won authority to offer a Bloom syndrome carrier status test indicated for detecting the BLMAsh variant in the BLM gene, based on saliva collected using an FDA-cleared collection device, the Oragene DX model OGD-500.001. The test is designed to assess users’ carrier status for the rare inherited gene disorder, which is characterized by short stature, sun-sensitive skin changes, an increased risk of cancer, and other health problems.

However, the company cautioned that it will not immediately begin returning Bloom syndrome carrier status test results—or any other health results—to customers until it completes regulatory reviews for additional test reports, and thus can offer a more comprehensive product offering.

“This is a major milestone for our company and for consumers who want direct access to genetic testing," Anne Wojcicki, 23andMe CEO and co-founder, said in a company statement. “We have more work to do, but we remain committed to pursuing a regulatory path for additional tests and bringing the health reports back to the US market.”

In addition to giving its authorization, the FDA said separately it will classify carrier screening tests for autosomal recessive disorders as “Class II” devices, and will issue a notice announcing its intent to exempt these devices from premarket review, with a 30-day comment period.

“The FDA believes that in many circumstances it is not necessary for consumers to go through a licensed practitioner to have direct access to their personal genetic information,” Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health, said in an agency statement.

The statement also justified FDA’s actions as supporting innovation and ultimately benefiting consumers. The agency was accused by free-market advocates of trampling on both in November 2013 when it ordered 23andMe to stop selling its Personal Genome Service and directed the company to seek approvals for its test. The agency cited what it called the potential public health consequences of inaccurate results from the PGS device.

23andMe’s Bloom syndrome carrier status test was evaluated through the de novo regulatory pathway, designed as an alternate path to classify new devices of low to moderate risk that are not substantially equivalent to an already legally marketed device. The de novo pathway was created by the Food and Drug Administration Modernization Act of 1997 (FDAMA). 

While devices that are classified through the de novo process may be marketed and used as predicates for future 510(k) submissions, 23andMe said it submitted its  application for review under standard 510(k) requirements. Because the direct-to-consumer test being reviewed was the first-of-its kind, the FDA determined that 23andMe's submission did not have an applicable predicate device, and converted it to a de novo request.

23andMe said it met FDA premarket requirements by demonstrating accuracy, validity and user comprehension, since its “spit kit” and chip array platform were validated for determining whether or not an individual is a carrier for the genetic markers for Bloom syndrome.

23andMe said it conducted “extensive” comprehension studies with consumers from different backgrounds, education levels and incomes, as well as an accuracy study performed at two lab sites with 70 samples. The samples included sixty-five saliva samples and five human cell line samples with known BLMAsh variant status. Results of the PGS test for Bloom Syndrome were compared with sequencing results, showing agreement in all 70 samples.

Also carried out was a validation study in which 2,880 sample replicates were run under standard 23andMe lab procedures, followed by an additional study of 105 saliva samples without the BLMAsh variant. Samples were tested by comparing results between both lab sites.

In addition, a user comprehension study was performed to assess how well people understood the PGS Bloom syndrome carrier status test reports. A sample desuigned to be representative of the US population reviewed and answered questions about the test report in a moderator-controlled setting.  More than 90% of participants indicated they understood the test results, 23andMe said.

Thursday, February 12, 2015

Source: © drizzd/Fotolia.com

Whole genome sequencing (WGS) is well on its way to transforming medicine. However, there are a few bumps on the road that WGS needs to overcome before it can become a broadly used and increasingly effective tool for the clinic. Current limitations include the need for WGS tests to be more reliable, demonstrate a better ability to capture the entire genome, and improve its predictive capabilities, which right now hinder the task of interpreting the results.

This GEN webinar will focus on scientific, clinical, and patient-oriented strategies to help WGS meet its high clinical expectations. Topics to be covered include whole genome sequencing strengths and weaknesses, transitioning from exome sequencing quality concerns and clinical utility to complementary issues with WGS, patients’ views on costs vs. benefits of WGS, potential risks associated with discrimination resulting from WGS data, regulatory and reimbursement issues, and themes revolving around privacy and patient ownership of WGS data. During the webinar Dr. David Smith will also point out specific clinical indications for which whole genome sequencing might be appropriate, Dr. Jason Park will talk about the need for improved standards covering whole genome sequencing and other techniques used in genomic medicine, and James O’Leary will provide the patient’s perspective on whole genome sequencing in the clinic.

To view this webinar cick here.

Thursday, February 12, 2015

A collaborative team of scientists have developed a new whole-genome sequencing technique to detect spontaneous mutations in IVF embryos. [3dmentat/Fotolia]

Since the first in vitro fertilization (IVF) birth in 1978 more than 5 million babies have been born using this method. In order to alleviate added stress for couples already experiencing difficulties to conceive, fertility scientists utilize pre-implantation genetic diagnosis (PGD) techniques to detect large chromosomal abnormalities or gene mutations that are passed along by parents to the IVF embryos.      

Unfortunately, it is not possible to systematically scan the entire genome of the embryo in order to detect spontaneous mutations. However, scientists from Complete Genomics, Reprogenetics, and the NYU Fertility Center believe they may have solved that problem.

Scientists from the collaboration have developed a whole-genome sequencing method that uses 5- to 10-cell biopsies from the in vitro embryos to scan for potentially detrimental mutations.    
The results from this study were published online in Genome Research in an article entitled "Detection and phasing of single base de novo mutations in biopsies from human in vitro fertilized embryos by advanced whole-genome sequencing".

Investigators sequenced three biopsies from two IVF embryos and searched for de novo mutations, those that emerge spontaneously in the egg or sperm and are not inherited by parental genes. Spontaneous mutations are believed to play a significant role in many congenital disorders such as autism, epilepsy, and some severe forms of intellectual disability.  

"Because each individual carries on average less than 100 de novo mutations, being able to detect and assign parent of origin for these mutations, which are the cause of many diseases, required this extremely low error rate," said co-authors Brock Peters, Ph.D., director of research and Radoje Drmanac, Ph.D., CSO at Complete Genomics.

Typically, 5 to 10 cells are biopsied from the blastocyst embryo, and the DNA is amplified before sequencing is performed. Due to lack of replication fidelity, the amplification process introduces thousands of errors, many of which are determined to be spontaneous mutations, leading to a false positive result. The current method that the collaborative teams have developed, which uses long fragment read technology, was able to eliminate over 100,000 sequencing errors or a 100-fold reduction over currently used clinical methods.

Overall, the researchers were able to detect 82% of all de novo mutations in IVF embryos. Interestingly, they did not find any mutations within the protein coding regions from the genome of one embryo, but another embryo from the same couple yielded two coding mutations in the ZNF266 and SLC26a10 genes. Mutations within these genes have led to serious diseases and defects. However, the scientists noted that they are currently unaware if the specific mutations they observed would lead to any detrimental health issues for the fetus.   

"The biggest hurdle now is one of how to analyze the medical impact of detected mutations and make decisions based on those results," said Dr. Peters and Dr. Drmanac.

In addition to the benefits for IVF, the scientists feel that their methodology could be employed for other clinical applications where trying to obtain cells is a challenge such as circulating tumor cells or circulating fetal cells. 

Tuesday, February 10, 2015

Source: © Robert Mizerek/Fotolia.com

Roche has acquired Signature Diagnostics for an undisclosed price. The deal is designed to strengthen Roche’s cancer diagnostics effort with Signature’s expertise in both biobanks and next-generation sequencing (NGS) assays, and is the pharma giant’s fifth deal in less than a year focused on molecular diagnostics and data analysis.

Signature will be integrated into Roche’s Sequencing Unit and will continue to focus on expanding its genomic signature portfolio.

Founded in 2004, privately-held Signature is a translational oncology and genomics company that develops large blood plasma and tissue biobanks in multiple cancers—including colorectal and lung cancers—constructed from multicenter prospective clinical studies.

Signature uses the samples from its biobanks along with accompanying clinical progression and genetic data to develop and validate circulating cell free DNA (cfDNA) tests for research use only, with the goal of advancing non-invasive treatment response monitoring for patients with cancer. Signature also develops several NGS assays, which use targeted gene panels and are also for research use only.

“Signature represents a unique bridge between high value cancer biobanks and NGS assay development.  Roche plans to leverage Signature's expertise in both of these areas to accelerate the development of targeted NGS-based diagnostics in the future,” Roland Diggelmann, COO, Roche Diagnostics, said in a statement.

Added Andre Rosenthal, Ph.D., Signature’s CEO: “We are very pleased Roche recognizes the importance of high-quality longitudinal cancer biobanks for the development of novel NGS-based diagnostics.”

Signature is the fifth deal in the past year aimed at building Roche’s molecular diagnostics business. Last month Roche said it will take a majority stake in Foundation Medicine (FMI) for $1.18 billion, launching a personalized medicine partnership intended to help develop new Roche cancer drugs by harnessing FMI’s capabilities in molecular information and genomic analysis.

In December 2014, the pharma giant said it was acquiring Ariosa Diagnostics for an undisclosed price to enter the non-invasive prenatal and cell-free DNA testing markets. Ariosa is a San Jose-based molecular diagnostics testing service provider that offers non-invasive prenatal testing (NIPT) through their CLIA laboratory using cfDNA technology. The deal was completed earlier this year.

Six months earlier in June 2014, Roche acquired Genia Technologies for up to $350 million— $125 million cash upfront, plus up to $225 million in milestone payments—to, the developer of a single-molecule, semiconductor-based, DNA sequencing platform using nanopore technology. Roche said at the time that Genia’s sequencing technology held potential for disrupting the market by reduce the price of sequencing while increasing speed and sensitivity.

And in April 2014, Roche snapped up IQuum for $275 million upfront and up to $175 million in product-related milestones, with the intent of strengthening its offerings in molecular diagnostics. The acquisition provided Roche with access to IQuum’s Laboratory-in-a-tube (Liat™) System, which enables healthcare workers to perform rapid molecular diagnostic testing in a point-of-care setting.

Roche’s sequencing unit is part of its Diagnostics Division, which saw sales rise 6% in 2014 to CHF 10.766 billion ($11.678 billion), driven by increases in its professional diagnostics (8%) and molecular diagnostics (6%) segments.

John Sterling

Sunday, February 01, 2015

The GGC, founded in 1974, is organized to provide clinical genetic services, diagnostic lab testing, educational programs, and research in medical genetics.

In October, the South Carolina-based Greenwood Genetic Center (GGC) launched a whole exome sequencing (WES) program. The technique, carried out via next-generation sequencing, is particularly appropriate for patients who need additional genetic testing, e.g., chromosome analysis and single gene sequencing, beyond traditional approaches. Bioinformatics specialists analyze the results to help narrow down the hundreds or thousands of gene variants, hoping that a single mutation can explain a patient’s condition.

A group led by Charles E. Schwartz, Ph.D., director of research and head of GGC’s JC Self Research Institute, has been investigating genes associated with autosomal forms of intellectual disability (ID) and autism, utilizing clinical material available at GGC.

For the rest of the story, click here.

MaryAnn Labant

Sunday, February 01, 2015

Source: Khakimullin / Deposit Photos

Many factors drive the next-generation sequencing (NGS) market in regulated environments. Only a few years ago, the throughput and price point did not allow for easy transition from existing technologies. The launch of benchtop instruments has significantly reduced the capital equipment costs and simplified the skill sets required for operation, expanding common near-term applications in noninvasive prenatal testing (NIPT), oncology, virology, drug-resistance testing, and infectious disease.

Scientists from around the world gathered to discuss the changing dynamics of NGS at a VIB event, Revolutionizing Next-Generation Sequencing: Tools and Technologies, which took place January 15–16 in Leuven, Belgium.

For the rest of the story, click here.

Chris Anderson

Sunday, February 01, 2015

Clinicians devoted to precision oncology are as effective as their computational infrastructure is robust. [Rbhavana/Deposit Photos]

Whether they are concerned with a mutation of a single gene, or mutations in a combination of two or more genes, today’s oncologists look forward to using genomic information to more precisely target and treat cancer. But as more and more researchers delve into the work of discovering which genetic mutations are associated with specific subtypes of cancer, or which drugs are most effective in fighting the cancers identified by their signatures, they begin to test the limits of their informational tools—computing platforms, informatics packages, and analytic algorithms. These digital factors are driving (and sometimes hindering) advances in developing more precise and targeted therapies for individual cancer patients.

Many of today’s challenges to increasing the precision of cancer treatment are directly related to both the complexity of data generated by genetic sequencing and the sheer volume of biomedical information contained in the published literature detailing new discoveries in the root causes of cancer and the drugs and therapies that most effectively treat it.

For the rest of the story, click here.

Sunday, February 01, 2015

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

Clinical OMICs Volume 2, Issue No. 2

Xing Wang, Ph.D., Zhenyu Sun, M.D., Xiaofeng Chen, M.D., Xiong Su, Ph.D., Gan Wang, Ph.D., and Matthew Kuruc

Sunday, February 01, 2015

Lung cancer is one of the most common malignancies and the leading cause of cancer-related fatality. In the United States alone, more than 210,000 new lung cancer cases are diagnosed every year, with more than 170,000 deaths resulting from the disease each year.

Current diagnostic practices for common cancers rely heavily on imaging technologies such as CT scans for lung cancer, mammograms for breast cancer, and pelvic ultrasounds for ovarian cancer. Given the high probability of false-positive findings associated with CT screening, there is a substantial need for additional noninvasive modalities to discriminate between benign and malignant nodules. There are similar challenges in imaging-based screening for other malignancies and a subsequent need for complementary diagnostic tests.

For the rest of the story, click here.

Alex Philippidis

Sunday, February 01, 2015

Increased scrutiny from the Office of Inspector General will force clinical labs to ensure that their practices are sound and their records complete. [WavebreakMediaMicro/Fotolia]

Washington will keep its eye on clinical laboratories this year—specifically, how much they are billing the federal government for services through Medicare.

The U.S. Department of Health and Human Services, through its Office of Inspector General (OIG), officially threw down the proverbial gauntlet to the labs in its Work Plan for the current federal fiscal year, which ends on September 30.

The Work Plan—the OIG’s annual report outlining its enforcement priorities for a given fiscal year—included for the first time “selected” independent clinical lab billing requirements.

For the rest of the story, click here.

Thursday, January 22, 2015

Source: © SSilver/Fotolia.com

A study, funded by the Movember Foundation and conducted by scientists at The Institute of Cancer Research (ICR) in London, has revealed several genetic mutations that may trigger the development of testicular cancer, in addition to uncovering a gene that may aid tumors in promoting resistance to existing drug therapies.

According to the authors, this is the first study of its kind to use whole-exome sequencing to probe testicular germ cell tumors, which constitute the majority of testicular cancer cases.

"This study has used the latest DNA sequencing technologies to provide a window into the development of testicular cancer, and reveals some potentially important clues as to how the disease could be treated more effectively,” stated Paul Workman, Ph.D., chief executive of ICR.

The investigators, whose research was published today in Nature Communications in an article entitled, “Whole-exome sequencing reveals the mutational spectrum of testicular germ cell tumours,” examined tumor samples from 42 patients with testicular cancer. They report previously unidentified chromosome duplications and confirmed data from earlier findings that associated these tumors with the KIT gene, which has been linked to an array of other cancerous tissues.

"Our study is the largest comprehensive sequencing study of testicular tumors published to date, describing their mutational profile in greater detail than has been possible using previous technologies,” says Clare Turnbull, Ph.D., senior author and  team leader in predisposition and translational genetics at ICR.

Interestingly, Dr. Turnbull and her team also found defective copies of the DNA repair gene XRCC2 in a patient who had become resistant to platinum-based chemotherapy. Their preliminary finding of a link between XRCC2 and platinum drug resistance was validated once they sequenced a sample from an additional platinum-resistant tumor. 

“We have identified new potential driver mutations for this type of cancer, and provided new evidence of a link between mutations in the gene XRCC2 and platinum treatment-resistant tumours. We now need additional studies with a larger number of patients, focusing in particular on platinum-resistant tumour’s, to help our discoveries lead to new options for those unlucky men whose cancer progresses in spite of the best available treatments," said Dr. Turnbull

Despite the fact that testicular cancer responds well to chemotherapy, about 3% of patients develop resistance to platinum-based drugs, which consequently is associated with a diminished long-term survival rate. This study provides essential general knowledge concerning testicular germ line cell tumor development, but more importantly, valuable insight into the genetic underpinnings as to why certain patients develop resistance to chemotherapy.

Thursday, January 15, 2015

Source: © Mopic/Fotolia

Scientists at the University of Michigan’s Comprehensive Cancer Center have uncovered genetic markers in a rare type of breast cancer called phyllodes tumors by wielding a powerful new tool in the molecular diagnostics arsenal: Next-Gen sequencing.

This comprehensive investigation of gene alterations, a first for phyllodes tumors, was published in the journal Molecular Cancer Research today under the title, “Next-Gen Sequencing Exposes Frequent MED12 Mutations and Actionable Therapeutic Targets in Phyllodes Tumors.”

While phyllodes tumors represent a small fraction (less than 1%) of breast tumors and are often benign, they are particularly aggressive in the their malignant state. Additionally, there are currently no reliable methods for predicting reoccurrence or malignant transformation after initial treatment. Nor are there many effective treatment options should malignancy occur.   

"We know little about the biology of phyllodes tumors” says principal investigator Scott A. Tomlins, M.D., Ph.D., assistant professor of pathology and urology at the University of Michigan Medical School. “In part, they have not been studied much because it's difficult to accumulate a large number of samples. Using these new sequencing techniques, we were able to study archived tissue samples, which allowed us to identify enough samples to perform a meaningful analysis."

Dr. Tomlins and his team obtained 15 samples of phyllodes tumors from the University of Michigan archives. These samples were dived equally in to three categories: benign, borderline, and malignant. Using Next-Gen sequencing, the researchers compared the phyllodes tumors samples against a panel of genes previously shown to have some functional role in other cancers.

The research team found two genes among the malignant phyllodes tumor set that were amplified, epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGFR1).  Due to their active role in other cancers, EGFR and IGFR1 have been a target for the development of a number of chemotherapeutic agents. The results from this current study would support assessing the currently available drugs in the treatment of phyllodes tumors.

In addition to the gene targets uncovered within the malignant tumor group, the investigators found a mutated gene, MED12, which was common in all three tumor sample categories. This gene has been shown previously to have a role in an array of cancer tissue types, but its occurrence in some rare gynecological cancers that are related to phyllodes tumors was of particular interest to Dr. Tomlins team. They suspect that MED12 could play a critical role in the tumor initiation step.   

“Taken together, this study defines the genomic landscape underlying phyllodes tumor development, suggests potential molecular correlates to histologic grade, expands the spectrum of human tumors with frequent recurrent MED12 mutations, and identifies IGF1R and EGFR as potential therapeutic targets in malignant cases.”

Tuesday, January 06, 2015

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

Clinical OMICs Volume 2, Issue No. 1

Nicola Brookman-Amissah

Tuesday, January 06, 2015

Figure 1. On-Bead Post-Capture PCR Amplification Enhances Enrichment. Target capture was performed using xGen® Lockdown® Probes and SeqCap® EZ Hybridization and Wash Kit. Relative levels of three target genes after enrichment were measured by qPCR.

Scientists at Geneseeq Technology share how to improve target capture for accurate clinical diagnostics by using optimized blocking oligonucleotides and stringent hybridization conditions.

The diverse array of mutations contributing to cancer complicates the selection of effective treatment regimens. There are only several hundred genes that can be targeted for cancer treatment, and the current trend is to selectively sequence these. Personalized medicine is helping clinicians to make informed treatment decisions and is facilitated by the latest next generation sequencing (NGS) technologies.

Target capture is a more pragmatic alternative to whole genome sequencing that focuses on selected genomic regions and presents an ideal approach for the routine clinical application of NGS. However, this technique must be carefully optimized to ensure accurate data.

For the rest of the story, click here.

Sean Tunis, M.D.

Tuesday, January 06, 2015

The rapid development of NGS-based tests for use in oncology has highlighted this technology’s tremendous potential to improve clinical care and patient outcomes.

After many years of steady development in DNA sequencing, the scientific community is reaching an exciting threshold in understanding the genetic riddles behind cancerous tumors. Newly developing next-generation sequencing (NGS) techniques can rapidly analyze large quantities of DNA, offering a greatly enhanced understanding of the molecular complexity of disease. NGS promises to accelerate the understanding of cancer, helping to define tumors’ biological pathways and their genetic characteristics. It is already beginning to yield a more accurate picture of disease and making possible an expanding choice of targeted therapies. However, assessing the clinical utility of NGS-based testing, as well as the benefits and risks of off-label prescribing of targeted therapies, are complex and controversial issues.

For the rest of the story, click here.

Chris Anderson

Tuesday, January 06, 2015

FDA has concerns over the adequacy of the scientific evidence supporting the use of many laboratory developed tests. [Kasto/Fotolia]

If the tenor of the overflow crowd at November’s Association for Molecular Pathology (AMP) Annual Conference to hear FDA’s Alberto Gutierrez, Ph.D., is any indication, the agency’s move to tightly regulate laboratory developed tests (LDTs) faces an uphill battle to win over those who run the thousands of molecular pathology labs across the country. Dr. Gutierrez, director, office of in vitro diagnostics and radiological Health at FDA, noted the agency was legally provided with regulatory oversight of tests developed in labs in 1976. But based on the types of “homebrew” tests used at the time, the agency decided to exercise regulatory discretion regarding LDTs.

But things have shifted dramatically over the past 40 years as companion diagnostics have multiplied in number and molecular pathology labs now routinely search for specific genetic mutations and other markers to both identify specific subtypes of cancer and to suggest precision therapies.

For the rest of the story, click here.

Gabriel A. Bien-Willner, M.D., Ph.D.

Tuesday, January 06, 2015

Source: Nelsonart­/Deposit Photos

We recently tweeted an article about researchers from The Icahn School of Medicine at Mount Sinai who had identified a genetic variant that might predict how cancer patients respond to radiation. One of our Twitter followers pointed out that simply showing a correlation means nothing. He has a great point—there are thousands/millions of genetic variants that exist, but not all of them are actionable for cancer treatment.

There is a lot we don’t know about cancer. We don’t even have a rigorous definition of what malignancy is. Nonetheless, most of the medical community would agree that cancer is a genetic disease.

For the rest of the story, click here.

Patricia Fitzpatrick Dimond, Ph.D.

Tuesday, January 06, 2015

The prenatal diagnostics industry is expected to reach $3.6 billion by 2019 with the demand for prenatal tests tripling over the next six years. [Mopic/Fotolia]

Prenatal screening for detection of a wide range of monogenic disorders and chromosomal abnormalities has been available to prospective parents for over 40 years. But these screening techniques, including seroscreening and ultrasound, have false positive rates of 5% and 10–15%, respectively, requiring that 1 in 20 women face a decision of whether to undergo invasive testing that may include amniocentesis, chorionic villus sampling, or, rarely, cordocentesis.

All of these procedures involve some risk with fetal loss rates of approximately 1 in 300 procedures, according to the American College of Obstetricians and Gynecologists (ACOG).

But the discovery of circulating fetal DNA (cfDNA) in the maternal circulation and the development of advanced sequencing technologies have led some scientists and clinicians to predict that antenatal diagnosis will become a predominately noninvasive process that will usher in the era of noninvasive prenatal testing (NIPT).

For the rest of the story, click here.

Alex Philippidis

Tuesday, January 06, 2015

Lab reimbursement is going through major changes, both in terms of coding and reimbursement. [Ki33/Fotolia­]

Clinical laboratories will be watching and waiting in the new year for the Centers for Medicare and Medicaid Services (CMS) to resolve several unsettled issues concerning fees for molecular pathology tests, as well as coding for drug-screening tests.

CMS approved 21 new codes for advanced genomic studies such as exome sequencing and whole genome sequencing, as well as a range of hereditary and cancer/somatic mutation genetic panels.

However, CMS directed instead that they be set in 2015 via “gapfilling.” Local Medicare Administrative Contractors (MACs) will set fee schedule amounts during the first quarter of 2015, to be released for public comment. The contractors will submit final prices in or about August 2015, with CMS expected to publish the medians and set 2016 prices at those medians.

For the rest of the story, click here.

Emily Chen, M.D., Ph.D., Pim Suwannarat, M.D., Christine Kobelka, MSc and Gemma Chandratillake, MPhil, Ph.D., MS, LCGC

Wednesday, December 10, 2014

Source: © kentoh/Fotolia.com

Next-generation sequencing has facilitated an explosion in clinical genetic testing, and for some patients with unknown disorders for which there were previously no genetic tests available, exome sequencing is now an option. The enhanced variety of clinical genetic tests brings increasing complexity for clinicians. Selecting the specific genetic test that is most likely to inform a molecular diagnosis for a particular patient is nontrivial. Deciding when to order a gene-panel test versus an exome-sequencing test can be particularly challenging and has prompted the recent development of different algorithms to aid in such decisions. Much of the difficulty surrounding test selection is derived from technological limitations of exome sequencing.1 If such limitations can be overcome, decisions could be simplified significantly, with exome and whole-genome sequencing replacing the need for large gene panels. A company that provides a comprehensive clinical exome-sequencing test is California-based Personalis.

For the rest of the story, click here.

Rob Fraser, Ph.D., and David Huntsman, M.D.

Wednesday, December 10, 2014

David Huntsman, left; Robert Fraser, right.

With unprecedented scientific advances over the last decade in genome sequencing, we now have an opportunity to make genomics testing a standard practice in cancer care. The valuable genetic information that genome sequencing can deliver will alter the future of cancer care from the current singular treatment approach toward tailoring treatment to more precisely match a patient’s genomic profile.

The National Access Project for Cancer Testing, managed by the Personalized Medicine Initiative with testing provided by Contextual Genomics, is designed to drive and facilitate a paradigm shift toward personalized cancer care in which medication selection will be selected on the basis of a patient’s genetic tumor profile. Physicians, patients, pharmaceutical companies, payers, and healthcare systems are advocating for personalized medicine because there’s no question of the benefits it will bring to healthcare. What we will gain from this tailored treatment approach is better health outcomes, reduced adverse drug reactions, patient empowerment, and a major cost-savings on health care systems.

For the rest of the story, click here.

Chris Anderson

Wednesday, December 10, 2014

Diagnostic firms are working to create new tests that can detect rheumatoid arthritis earlier and also provide risk assessment profiles of patients that are more or less likely to suffer permanent physical damage as a result of the disease. [©Puwadol Jaturawutthichai/Shutterstock]

In oncology, more precise treatments for many different forms of cancer are in the offing, a prospect that makes oncologists the envy of other healthcare professionals. Already, cancer companion diagnostics can show doctors the specific drug that will be most effective in treating a particular subtype of cancer. Unfortunately, such specificity does not yet exist for diagnosing autoimmune diseases such as lupus, Sjogren’s disease, and rheumatoid arthritis.

More definitive diagnostics are needed for autoimmune diseases. Technologies capable of predicting drug responses would be especially welcome. But there are many development challenges: autoimmune symptoms are similar to symptoms of many other diseases; the disease pathways for many autoimmune disorders aren’t clear; and autoimmune diseases are systemic—unlike solid tumor cancers, which start as highly localized disease.

For the rest of the story, click here.

Harry Glorikian

Wednesday, December 10, 2014

Using NGS to detect cell-free DNA and other biomarkers could transform cancer care. [© Photographee.eu/Fotolia.com]

More than 40 years after President Nixon declared the War on Cancer in 1971, we are losing that battle. According to the American Cancer Society, 1.67 million new cancer cases will be diagnosed in the United States in 2014. About 586,000 Americans and six million people worldwide will die of cancer in 2014. Despite massive investments in treatment and prevention, cancer mortality among people under 85 in the United States has fallen a meager 8% since 1975. This has led many to wonder if our current strategy makes sense. As Einstein once said, insanity is doing the same thing over and over again and expecting different results. Will the “cure” for cancer come from more blockbuster drugs, or is the answer much simpler and now within our grasp?

Spending on cancer therapeutics is massive, with worldwide sales of $85 billion in 2013,1 and multiple drugs with $100,000 plus price tags on the market. However, on average, only a quarter of patients respond to any particular treatment—that’s a dismal response rate, and few of those are actual cures.2 This feverish focus on cures has dominated the research since President Nixon declared war on the disease in 1971. But the results are disheartening at best. As shown in Figure 1, this approach has yielded meager results; as mentioned earlier, the overall cancer mortality rate in the United States for ages younger than 85 years has fallen by a meager 8% since 1975. Heart disease deaths by comparison have dropped a whopping 60% or so—many times more than cancer deaths.

For the rest of the story, click here.

Alex Philippidis

Wednesday, December 10, 2014

Economic models for evaluating genomic data must consider both the costs and benefits of obtaining the data and delivering the treatments. [© Tameek/Fotolia]

2014 may have been the year the “$1,000 genome” became reality. But it’s ultimately a small piece of a much bigger
puzzle, the economics of genomic medicine and translating that value into actual health benefits to patients—that will continue to vex researchers and clinicians into the new year and beyond.

The falling cost of sequencing and other tools for extracting genomic data will be more than made up by the expenses labs and medical practices will face not only analyzing the growing deluge of raw data, but clinically interpreting those results. Yet genomic economics is also being shaped by factors beyond numbers—from data quality and quantity, to patient behavior, to the actions of payers.

“It’s not the cost of the test, per se, that’s going to be driving the economic decision making. It’s how the information is conveyed to providers and patients, and how they respond to it that is a first-order concern to an insurer, or someone thinking about implementing genetics in clinical practice,” John A. Graves, Ph.D., Assistant Professor at Vanderbilt University School of Medicine, told Clinical OMICs.

For the rest of the story, click here.

Patricia Fitzpatrick Dimond, Ph.D.

Wednesday, December 10, 2014

Trovagene has developed methods for isolation of the short, fragmented nucleic acids that pass through the kidneys and has created genomic and mutation panels offered through its CLIA-licensed lab. [LLEPOD/Deposit Photos]

Noninvasive molecular diagnostics based on cell-free DNA analysis are advancing as more methods have been developed to detect and quantitate nucleic acids from blood and urine. Recent studies suggest that genomic alterations in solid cancers can be characterized by massively parallel sequencing of circulating cell-free tumor DNA released from cancer cells, then excreted into urine or plasma.

Circulating tumor DNA (ctDNA) represents a promising biomarker for sensitive, specific, and dynamic detection of disease burden in cancer patients, investigators say. Additionally, ctDNA analysis allows noninvasive access to cancer genomes for tumor genotyping and monitoring of resistance mutations, enabling “liquid biopsy” from urine and plasma to assess tumor status.

For the rest of the story, click here.

Wednesday, December 10, 2014

MilliSect is a mesodissection instrument that enables efficient dissection from slide-mounted tissue for both clinical/research pathology and histology laboratories. [AvanSci Bio]

Roche Diagnostics signed a deal with AvanSci Bio to buy all products associated with the high- performance microdissection of slide-mounted tissue sections. The system consists of instrumentation, software, and consumables used by researchers and clinicians to extract specific areas of tissue with high precision and purity for subsequent molecular analysis including real time PCR, microarrays, and sequencing.

AvanSci Bio's technology includes the automated MilliSect™ instrument which reportedly enables a greater than 90% tumor enriched sample for molecular analysis. The system will be tested at select customer sites in 2015 as part of a broader development program for a future generation instrument.  MilliSect targets a 100mm2 to 100 µm2 level of resolution (what AvanSci refers to as " meso" dissection range).

"This innovative system will expand our diagnostic tool kit allowing us to link the diagnostic hematoxylin and eosin (H&E) stain with sequencing analysis through high quality sample preparation," said Dan Zabrowski, head of Roche Tissue Diagnostics and Sequencing Solutions. "It will also enable us to meet the critical challenge of tumor heterogeneity."

Tumor tissue staining gives researchers and clinicians important information about both tissue context and spatial relationships and tumor heterogeneity (which stems from the evolution of multiple subclones within the tumor). Information obtained from stained areas enable researchers and clinicians to pinpoint and extract more precise regions of interest within the tissue, resulting in purer samples of sufficient quantity that can then be used for sequencing. In addition, the analytical sensitivity of sequencing improves with higher sample purity as does subsequent data analysis and interpretation.

Tuesday, December 09, 2014

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

Clinical OMICs Issue 15

Tuesday, December 02, 2014

© Voyagerix/Fotolia

Roche is acquiring Ariosa Diagnostics, a San Jose-based molecular diagnostics testing service provider that offers non-invasive prenatal testing (NIPT) through their CLIA laboratory using cell-free DNA (cfDNA) technology.

Ariosa’s Harmony Prenatal Test is designed to assess the risk of Down syndrome and other genetic abnormalities by evaluating fetal cfDNA found in maternal blood. Specifically, the test assesses the risk of trisomies 13, 18, and 21, which are indicative of an extra chromosome in the fetus that can lead to severe genetic conditions. Harmony has a less than 0.1% false-positive rate, according to the company.

“The acquisition of Ariosa is another example of Roche’s commitment to advanced molecular diagnostics,” said Roland Diggelmann, COO Roche Diagnostics Division. “Circulating cfDNA has the promise of providing early diagnostic information through a simple blood test in many important segments including pregnancy, cancer, and transplantation, aligning with our strategy in personalized healthcare and commitment to setting new standards of care.”

In April, Roche acquired IQuum to strengthen offerings in molecular diagnostics. The acquisition provided Roche with access to IQuum’s Laboratory-in-a-tube (Liat™) System, which enables healthcare workers to perform rapid molecular diagnostic testing in a point-of-care setting. 

Tuesday, November 25, 2014

© Monkey Business/Fotolia

Thermo Fisher Scientific and Samsung Electronics will jointly design, develop, and market new point-of-care (POC) solutions in key applications, such as the detection of sepsis, drugs of abuse, and therapeutic drug monitoring as well as the detection of cardiac problems and women’s health conditions.

“Samsung has developed a compelling and innovative suite of POC platforms,” said Marc Tremblay, Ph.D., president of Thermo Fisher’s clinical diagnostics business. “We look forward to working with Samsung to add some of our leading biomarkers and assays to their platforms to create a truly differentiated testing menu.”

“We are very excited to leverage Thermo Fisher Scientific’s strong commercial sales and service channels, as well as the potential to offer a broader range of tests to our customers and their patients,” said Soo-In Cho, president and head of the health and medical equipment business at Samsung. “This strategic collaboration combines the strengths of two industry leaders to accelerate POC innovation and more rapidly bring solutions to market.”

This year, Thermo has affirmed its personalized medicine ambitions. In September, the company entered an agreement with GlaxoSmithKline and Pfizer to develop a universal next-generation sequencing oncology test for solid tumors that will serve as a companion diagnostic for multiple drug programs. 

Wednesday, November 19, 2014

DxTerity’s goal is to make genomic testing a routine part of healthcare. Currently, costs are too high for standard use. DxTerity’s Dx Direct platform lets doctors run a wide variety of genomic tests from a single drop of blood at an affordable price.

Genomic technologies enabling relatively simple, rapid, and costeffective high-throughput testing of RNA-based multiplexed signatures in blood samples would greatly facilitate wide-scale adoption of molecular diagnostic tests in clinical medicine. Tests like CardioDx’ Corus CAD and CAREDx’ Allomap represent the first generation of products designed to improve diagnosis, predict therapeutic response, monitor drug responses in patients, and determine disease prognosis from a simple blood draw. This emerging class of tests known as IVDMIA tests is demonstrating value in clinical applications, and many researchers are developing assays with these methods.

One group of researchers, Shi et al., recently reported the development of blood-based, three-gene signatures for the noninvasive detection of early human hepatocellular carcinoma. These scientists used comprehensive gene expression profiling of purified RNA of peripheral blood mononuclear cells (PBMCs). Gene signatureswere developed through bioinformatics-driven approaches, and their diagnostic value was evaluated by custom-designed, quantitative, multiplex PCR assays.

But several factors including the technical complexity of current testing platforms, the high cost of materials and labor to perform them, and the limited availability of validated tests limit wide clinical use of RNA-based expression signatures. Other limitations include the need for RNA stabilization by freezing or by addition of a chemical denaturant that inactivates RNases. These chemical denaturants inhibit downstream amplification and assay methods.

For the rest of the story, click here.

Mary F. Lopez, Ph.D.

Wednesday, November 19, 2014

Figure 1. A BRIMS scientist connects up an ion source, which is often used in proteomics experiments.

Combining genomic and proteomic techniques can reveal important insights to unlock complex biological function. The exploration of methods for integrating large genomic and proteomic datasets is gaining traction due to improved bioinformatics and the public availability of well-organized, searchable data. Also, by merging RNA sequencing with mass spectrometry and improving bioinformatics, scientists can strategically select from a much broader range of investigational techniques and take advantage of complementary information. When one avenue of investigation closes, another may offer a new route to discovery—either building on previously inconclusive results or offering altogether new insights. Multiple studies in the past several years have demonstrated that transcriptional profiling data do not necessarily correlate with protein expression data, confirming that the two types of information are not duplicates but, instead, may be synergistic in terms of broadening our understanding of basic biology.1

In this brief overview, three recent examples illustrate how a “proteogenomics” approach can improve investigational power by enabling a progression of approaches that lead to actionable conclusions. When it comes to translational medicine, proteogenomics may provide better prospects for revealing biomarkers, assessing disease states, and identifying the complex mechanisms behind biological function (Figure 1).

For the rest of the story, click here.

MaryAnn Labant

Wednesday, November 19, 2014

Qiagen’s QuantiNova kits have a built-in tracking system for visual identification of correct pipetting.

The polymerase chain reaction (PCR), invented about three decades ago, soon entered mainstream use thanks to an ongoing series of refinements.

One particularly important refinement, introduced about two decades ago, is the “real time” quantification of DNA. The idea is to trace the rising level of DNA throughout the amplification step, and not just measure the final amount of amplified product. This idea turns standard PCR into real-time PCR, or quantitative PCR.

Real-time PCR has become the most widely used nucleic acid detection technology. It is routinely used in academic research, in applied testing settings such as food-safety or veterinary testing, and in molecular diagnostics. It continues to replace many older detection methods due to simple readouts, high sensitivity, and multiplex and quantification capabilities, as well as ease of use, cost effectiveness, and throughput flexibility with only moderate equipment investments.

According to Peter Urbitsch, Ph.D., head of the global assay technologies business at Qiagen, real-time PCR technology has evolved and diversified in multiple directions. Available formats include tubes, microarrays (96-, 384-, and 1,536-well plates), and capillary and rotor variants. Detection principles include SYBR green and probe-based detection, with the latter being increasingly diversified into FRET, Scorpions, TaqMan, and others. In addition, multiplex detection formats are being developed using different dyes and quencher molecules.

For the rest of the story, click here.

Jeffrey N. Gibbs

Wednesday, November 19, 2014

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On July 31, the Food and Drug Administration (FDA) notified Congress that it intended to issue two draft guidances regulating Laboratory Developed Tests (LDT’s). See our previous coverage. While the Energy and Commerce Committee House Subcommittee on Health did hold a hearing on September 9, Congress took no steps to block the issuance of the documents. On October 3, 67 days after notifying Congress, FDA published the proposal in the Federal Register.

The documents released on October 3 differed in only two minor respects from the proposals provided to Congress. Reflecting the significance of these documents (and also to avoid conflicts with the holidays), FDA did provide a 120-day comment period, which is longer than usual for guidance documents.

In releasing the draft guidance documents, FDA asked commenters to specifically address certain topics. Even before releasing the documents for comments, FDA had received initial feedback from various parties. Presumably, the areas which FDA highlighted will be ones for which the agency is particularly receptive to modifying its proposal.

For the rest of the story, click here.

Kate Marusina, Ph.D.

Wednesday, November 19, 2014

Illumina’s MyGenome App for iPad simplifies visualizing and exploring the human genome.

The explosive growth of DNA-based diagnostics empowers us to take a closer look at our own health and to demand answers from healthcare providers to questions that have never been asked before. Even if we do not fully understand the clinical relevance of most of the genetic changes, the information that has been validated is significant enough to change the status quo of medical care.

It is only natural that mobile devices are tapped for their unprecedented power and flexibility to deliver physiological data and lab results when and where it is needed most. As the maturing world of mobile devices meshes with the rapidly emerging word of genomics and biosensors, medicine could literally be found at our fingertips. This powerful combination not only gives more tools to treat the existing conditions but could also shift medicine into a true preventative mode.

Some visionaries hypothesize that mobile data will eventually lead to the demise of brick-and-mortar hospitals. One such visionary, geneticist and cardiologist Eric Topol, M.D., advocates the widened use of wearable, wirelessly networked biosensors to advance personalized medicine. In his popular book, “The Creative Destruction of Medicine,” Dr. Topol even anticipates that digital tools could empower a consumer-led democratization of medical care.

For the rest of the story, click here.

Chris Anderson

Wednesday, November 19, 2014

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Since the development of the first companion diagnostic for Herceptin was introduced more than 10 years ago, the development paths for these tests have followed the same formula: stratify patients by identifying a single marker that can predict the likelihood that a single therapeutic will or won’t be an effective form of treatment.

From a clinical standpoint, a companion diagnostic (CDx) seeks to close the gap between a “one size fits all” approach to using a drug and a tailored approach to using the drug in an individual patient. The bulk of the companion diagnostics available for clinicians target oncology drugs and have been developed as researchers have come to better understand the mechanisms, pathways, and manifestations of cancer, all helping to answer the age-old conundrum of why certain patients respond to therapy while others show no improvement.

In short, a companion diagnostic helps clinicians determine the safest and most effective use of a drug for only those patients who stand to benefit from it. On the flip side, it also helps avoid unnecessary treatment for patients who won’t respond, which allows doctors to seek alternate treatment routes right away—an especially important consideration for oncologists to avoid wasting time on ineffective treatment. A CDx test can also help identify patients that may have a significant adverse reaction to a drug.

For the rest of the story, click here.

Wednesday, November 19, 2014

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

Clinical OMICs Issue 14

Thursday, November 13, 2014

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ARUP Laboratories will join the PierianDx partner network to share tools, assays, and clinical information in an initiative to improve the personalized interpretation of next-generation sequencing (NGS) clinical diagnostic tests.

ARUP will use PierianDx’s workflow management tools and NGS knowledge base to more effectively and quickly access its own knowledge base of variants and clinical outcomes, as well as benefit from the collective insights of other institutions in the PierianDx partner network, the company said. PierianDx offers a bioinformatics platform, workflow solution and software, and clinical information from thousands of previous genomic tests.

“Our expectation is that by leveraging PierianDx’s visionary software and database, we will be able to more effectively learn from past assays and provide even more personalized recommendations to physicians so they can better match their patients to the right therapies,” said Edward Ashwood, M.D., president and CEO at ARUP.

“By teaming with ARUP, the PierianDx partner network will benefit from insight provided by ARUP clinical interpretations, variants, and related de-identified patient information,” said Ted Briscoe, CEO. “All of our partners will be able to leverage our expanding knowledgebase to improve personalized diagnosis and care.”

ARUP offers more than 3,000 tests and test combinations, ranging from routine screening tests to highly esoteric molecular and genetic assays. Last month, ARUP announced that it was offering high-resolution HLA genotyping by NGS under an agreement with the Children’s Hospital of Philadelphia. In July, ARUP signed an agreement with University Hospitals Case Medical Center to distribute the DEEPGEN™ HIV test.

Jonathan Frampton, Ph.D.

Wednesday, November 05, 2014

Figure 1. Potential for variability in molecular diagnostics workflow

Companion diagnostics are bridging the gap between molecular diagnostics and therapeutics, helping to ensure that the right drug is provided to the right patient at the right time. Personalized medicine, with the aid of molecular diagnostics, is providing the exciting possibility of the delivery of cost-effective tailored therapies, based on an individual patient’s genetic code. This is particularly true in the case of cancer.

When applied correctly, companion diagnostics can help identify not only patients who are most likely to benefit from a particular therapeutic product, but also those likely to be at increased risk for serious side-effects as a result of treatment. Accurate diagnostics can also monitor response to treatment with a particular therapeutic product, to achieve improved safety.

As of October 2014, there were 19 FDA-authorized companion tests being used to support decisions on the particular therapy that a patient receives.

For the rest of the story, click here.

Alex Philippidis

Wednesday, November 05, 2014

PROMPT, an online registry for patients who have undergone hereditary cancer testing, is being developed by Ambry Genetics and several institutional partners.

The “Father of Modern Medicine” is also the father of patient registries. Hippocrates (c. 460 BC–c. 370 BC) urged doctors to record the symptoms they observed daily in their patients: “The physician must be able to tell the antecedents, know the present, and foretell the future.” (Of the Epidemics, c. 400 BC).

The first modern registries, focused on patient populations with specific diseases, emerged in the 20th century, with their use expanded for disease- and drug-based research by the 1980s. Now, in the age of Big Data, the registries give new meaning to community organizing by growing, or planning to grow, into sources of some of the most valuable data around—namely, the experiences of patients, and the genetics behind them.

For the rest of the story, click here.

Kathy Liszewski

Wednesday, November 05, 2014

One of the major roadblocks to successful biomarker development is an inadequate specimen procurement process. [Science Photo/Fotolia]

Tailoring healthcare decisions based on biological information represents the promise of personalized medicine. A key hurdle slowing progress toward tailored therapeutics is developing appropriate biomarkers for diagnostics, prognostics, and prediction.

Despite much research, only a trickle of biomarkers has made it into clinical practice. Researchers, however, are pursuing novel avenues and making headway by dissecting the subtle architecture of normal versus cancerous cells. New approaches include scrutinizing aberrant glycans, microRNAs shed from tumors, and epigenetic modifications, as well as mining and merging the vast stores of multi-omics data.

For the rest of the story, click here.

Wednesday, November 05, 2014

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

Clinical OMICs Issue 13

Wednesday, November 05, 2014

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Roche said today it will establish a CHF 450 million ($467.2 million) diagnostic manufacturing facility at China’s Suzhou Industrial Park, the pharma giant’s eighth worldwide and first in the Asia-Pacific region.

The facility – set to become fully operational by 2018 – will focus on producing immunochemistry and clinical chemistry tests and will grow its workforce to more than 600 people “over the next several years,” Roche said.

“The new manufacturing site will enable us to meet the growing demand for our diagnostic products, ensuring our continuous contribution to the health of people in China and the Asia Pacific region,” Roland Diggelmann, COO of Roche Diagnostics, said in a statement.

Roche now employs more than 4,000 people in 15 countries across the Asia-Pacific region, where it has had a presence for 40 years. In China, Roche became the first foreign-based pharma giant to open a drug-discovery research center in 2004 at Zhangjiang Hi-Tech Park.

This year, the region has generated the fastest growth for Roche Diagnostics, with first-half 2014 sales rising 15% over the first six months of 2013, to CHF 877 million ($910.4 million). Asia-Pacific sales growth reflected in part demand for professional diagnostics.

“The sales increase in Asia–Pacific was also influenced by increasing sales in China (+24%) coming from governmental healthcare investments, public demand and the division’s expanding presence and wide portfolio,” Roche stated in its Half-Year Report 2014, covering January-June results.

While a Roche sales office in Hangzhou was “visited” earlier this year by local authorities investigating the practices of multinational pharmas, the company has not experienced the official wrath visited upon GlaxoSmithKline, which in September was fined almost $500 million by a Chinese court that meted out prison sentences to five of its former executives.

Roche also strengthened its Asia-Pacific presence last year by launching a partnership with Ascletis to develop and commercialize Roche’s investigational small-molecule NS3/4A protease inhibitor danoprevir in China for Hepatitis C virus. Ascletis agreed to fund and oversee development, regulatory affairs and manufacturing of danoprevir in greater China – including Taiwan, Hong Kong and Macau – in return for an undisclosed amount of development and commercial milestone payments from Roche, plus royalties.

Patricia Fitzpatrick Dimond, Ph.D.

Wednesday, November 05, 2014

The NCI is funding research to determine whether outliers from failed clinical trials can reveal hidden drug development possibilities. [francisblack/IStock Photos]

We have all heard stories about the single patient who survives a deadly cancer in response to a particular drug, in contrast to other patients receiving the same drug who succumb to the disease.

These patients may include heavily pretreated cancer patients for whom other drugs have failed, but then who respond to a therapy not typically used to treat their type of cancer. Now, with novel genomics tools at their disposal, investigators say that by analyzing the drug responses of “n-of-1,” patients who are single outliers in clinical studies, new insights into cancer mechanisms and more effective treatments can be gained. 

For the rest of the story, click here.

Thursday, October 23, 2014

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The University of Oxford is partnering with the Chan Soon-Shiong Institute for Molecular Medicine (CSSIOMM) to establish the first center in the U.K. designed to support the delivery of individualized, data-driven molecular-based medicine for NHS cancer patients. The new center, dubbed the Chan Soon-Shiong Oxford Center for Molecular Medicine (CSSOCMM), will be collaborating with the Oxford University Hospitals NHS Trust. 

The Chan Soon-Shiong Institute is initially investing $50 million to advance clinical cancer care in the U.K. through genomic and proteomic-driven diagnoses. These funds, CSSIOMM says, will provide doctors with large-scale sequencing capabilities for patient-level genomic, epigenomic, proteomic, and digital pathology data capture as well as tools and supercomputing technology to help clinicians make decisions regarding cancer treatments.

The CSSOCMM will be co-located with a new Precision Cancer Medicine Institute also announced today, where the clinical applications of its research will happen. It will also have links with the Target Discovery Institute and Big Data Institute, all of which are a part of an investment in cancer diagnosis and treatment being made by the University of Oxford over the next five years.

"Along with the University of Oxford, we are living our commitment to clinicians and patients alike," commented Patrick Soon-Shiong, M.D., founder and chairman of CSSIOMM, in a statement. "Using the most advanced, sophisticated tools imaginable, we’re on a mission to solve the mystery of cancer, and establish an adaptive learning system where the power of one can inform many."

"This investment highlights the international confidence in the UK’s ability to develop better and more personalized cancer treatments that can make a real difference to patients—especially in rare disease and cancer," George Freeman, the U.K.'s Minister for Life Sciences, commented about the announcement at a press conference in London. "The Prime Minister and I are determined to make Britain the best place in the world to discover and develop 21st century medicines."

This is CSSIOMM's third partnership this year; the Providence Health System and Phoenix Children's Hospital have also received CSSIOMM grants within the past six months.

Thursday, October 23, 2014

Source: © Dana Britton - Fotolia.com

Akers Biosciences inked a joint venture agreement with Hainan Savy Investment Management to research, develop, produce, and sell certain Akers’ rapid diagnostic screening and testing products in China. The joint venture company will be located in Haikou and incorporated as Hainan Savy Akers Biosciences.

As part of the agreement, the companies plan to market and sell the majority of Akers’ product line, with a special emphasis on diabetes, cardiac, and infectious diseases rapid diagnostic screening and testing products.

The headquarters will be located in the Haikou National Hi-Tech Industrial Zone and a manufacturing operation will be established in the same area.  The business will be structured to utilize numerous government incentives intended to develop and promote the Chinese diagnostic industry.  Other market opportunities in Asia will also be explored, the companies said.

Akers offers several diagnostic screening and testing products internationally, including its Breath Ketone test for diabetic monitoring, CHUBE disposable breath alcohol detectors, Tri-Cholesterol test, and particle immunofiltration assay based tests for infectious diseases such as chlamydia, dengue fever, malaria, and syphilis.

Chris Anderson

Wednesday, October 22, 2014

The power of new sequencing technologies is their ability to unlock information about the variable nature of solid tumors to provide clinicians with a better understanding of cancer’s mechanisms. [© Monika Wisniewska/Fotolia]

There is little doubt that the future of solid tumor cancer treatment will be increasingly precise and tailored to individual patients based on specific predictive biomarkers. Next-generation sequencing (NGS) technologies, which have become more refined in just the past few years, are a leading breakthrough that has allowed researchers and molecular pathologists alike to shift from querying single genes to panels that can simultaneously examine 40, 50, to even hundreds of genes in one run.

This is not to say that NGS will be the silver bullet of personalized cancer treatment, as there is a wide array of genetic tests available today to predict the risk of developing specific cancers and ones that also help target specific therapies to cancer subtypes. Rather, the power of these new sequencing technologies will be to unlock information about the variable nature of solid tumors to help provide clinicians with a better understanding of cancer’s mechanisms. Using this information, they can choose from the rapidly expanding roster of cancer therapeutics, specifically which one is most appropriate to best treat an individual patient based on the genetic profile of their cancer.

For the rest of the story, click here.

Patricia Fitzpatrick Dimond, Ph.D.

Wednesday, October 22, 2014

One novel technique for capturing clinically important low-abundance proteins is to create core-shell hydrogel nanoparticles containing high affinity reactive chemical baits for protein and peptide harvesting and concentration. [AlexRaths/iStock Photos]

Many scientists point out that it’s become clear there are no simple universal strategies for the comprehensive analysis of complex proteomes. Although the application of omics technologies to biological samples generates hundreds to thousands of biomarker candidates, a small number actually make it through the pipeline to clinical use, largely due to the incredible mismatch between the large numbers of biomarker candidates and the paucity of reliable assays and methods for validation studies.

Currently, the main technology platform for systematically interrogating large numbers of proteins is based on multiple reaction monitoring (MRM) mass spectrometry (MS). However, a substantial challenge in using MRM-MS for targeted peptide analysis in clinical proteomics applications is the prevalence of interfering peptides and small molecules in the sample matrix. This problem, although well studied for small molecule analysis, is both less well recognized and far more severe for peptide analysis because peptide MRM analyses are typically carried out in an ocean of many hundreds of thousands to millions of peptides produced by digestion of the 10,000 or more proteins found in blood and other tissues.

For the rest of the story, click here.

Summer E. Allen, Ph.D.

Wednesday, October 22, 2014

The predicted secondary structure of peptide p5+14. The peptide is alpha helical with all the charged lysine residues on one face of the helix. [University of Tennessee]

Researchers are developing a host of new uses for molecular imaging techniques—including magnetic resonance imaging (MRI), positron emission tomography (PET), and single photon emission computed tomography (SPECT)—that are already commonly used in patient care. Once these techniques have picked up new capabilities in the laboratory, they will return to the clinic, where they will likely transform the diagnosis and treatment of cancer and other diseases.

“The approval rate for new therapeutic entities in oncology is the lowest of all disease areas. Ninety percent of new chemical entities that go into clinical testing for cancer fail—despite the fact that they are all backed with tons of animal data suggesting that they should work,” says Andrew Kung, M.D., Ph.D., director of pediatric hematology, oncology, and stem cell transplantation, New York-Presbyterian Morgan Stanley Children’s Hospital/Columbia University Medical Center.

Dr. Kung has been at the forefront of a movement to improve preclinical animal studies—primarily by using more representative animal models of cancer and by measuring treatment response using molecular imaging and other techniques that might also be used to measure desired responses in patients.

For the rest of the story, click here.

Barbara M. O'Brien, Edward M. Kloza, Jacquelyn V. Halliday, Geralyn M. Lambert-Messerlian, and Glenn E. Palomaki

Wednesday, October 22, 2014

Researchers have found a growing understanding and acceptance by pregnant women of ccfDNA testing. [© igorborodin/ Fotolia]

In October 2011, the Sequenom Center for Molecular Medicine (SCMM) became the first laboratory in the United States to offer next-generation sequencing of circulating cell-free (ccf) DNA testing for Down syndrome (trisomy 21). This commercial launch followed the publication of an external clinical validation study demonstrating that testing could identify 98.6% of fetuses with Down syndrome (209/212) with a 0.2% false-positive rate (FPR) (Palomaki et al., 2011). In a later publication derived from that same high-risk cohort, 100% cases of trisomy 18 interpreted (59/59) were detected (FPR=0.28%) as were 91.7% (11/12) cases of trisomy 13 (FPR=0.97%) (Palomaki et al., 2012). Less than 1% of samples failed testing, including both case and control samples.

This level of performance is much better compared with the existing serum screening tests, offering the potential to reduce the number of invasive procedures (chorionic villus sampling [CVS] or amniocentesis) among high-risk women substantially, while maintaining detection of these common trisomies. The American Congress of Obstetricians and Gynecologists has recommended that women, regardless of age, be offered prenatal assessment for aneuploidy by screening or invasive prenatal diagnosis (ACOG, 2007). However, ccfDNA testing is currently recommended as a secondary screening test in women already identified at increased risk of aneuploidy (ACOG, 2012). Our prenatal diagnostic center planned on routinely offering ccfDNA testing to high-risk women receiving genetic counseling and sought to document implementation issues and women's decision-making encountered in the early introduction of this technology.

For the rest of the story, click here.

Naomi O’Grady

Wednesday, October 22, 2014

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The application of genomics in cancer has led to an improved understanding of the disease. To date, 125 driver genes have been discovered—71 tumor suppressors and 54 oncogenes—that promote tumor growth through 12 cellular signaling pathways.1 These pathways have become the focus of small molecule inhibitor drugs, primarily targeting kinases. While the number of available targeted therapies is limited, more than 800 oncology drugs are in development, many of which are designed to target specific mutations.2

Yet, the tumor genomic landscape is heterogeneous and researchers are finding that it evolves as cancer progresses. While single-analyte companion diagnostics exist, they require investigators to assay each target sequentially. The process is costly, time consuming, and in many cases exhausts the limited tissue available for analysis.

For the rest of the story, click here.

Wednesday, October 22, 2014

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

Clinical OMICs Issue 12

Friday, October 10, 2014

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Precision cancer therapy firm Perthera is partnering with the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and the Northwestern Medicine Developmental Therapeutics Institute (NMDTI) to conduct a translational research program aimed at assessing the utility of integrating next-generation sequencing, proteomic, and phospho-proteomic data in oncology developmental therapeutics and clinical practice. Under the alliance, the three organizations plan to develop clinical protocols incorporating Perthera's approaches and methodologies to cancer protocol treatment and to assess their impact on overall disease management and patient outcomes.

Perthera provides molecular diagnostic testing, profiling, and analysis services to create an analysis of a patient's individual cancer. The firm says it pairs proteomics with genomic analysis in the context of patient history to help oncologists identify personalized options for treating individual patients.

Lurie Cancer Center director Leonidas C. Platanias, M.D., Ph.D., said in a statement that the center—which says it is one of only 41 NCI-designated "comprehensive" cancer centers in the U.S.—considers this alliance with Perthera an important component of its focus on applying personalized medicine at both the individual patient and research protocol levels. "The rapid identification of cancer drivers and the attendant continuous expansion of our pipeline of cognate therapies that are directed at these targets is a major focus within our institutes," added Francis J. Giles, M.D., associate director for translational medicine and developmental therapeutics at the Lurie Cancer Center and director of the NMDTI.

The Lurie Cancer Center and NMDTI aren't the only institutions that have expressed interest in Perthera over the past year: Last June, the Pancreatic Cancer Action Network partnered with Perthera to identify relevant pathways and mutations for pancreatic cancer including previously unidentified targets.

Friday, October 10, 2014

Total Glut4 glucose transporter (left, green) and cell-bound Glut4 (right, red). Cell-bound Glut4 is increased in presence of insulin and a FAHFA lipid. [Weill Cornell Medical Center, Salk Institute and Beth Israel Deaconess Medical Center]

An exhaustive analysis of fatty acids from a diabetes-protected animal model has revealed a whole new class of molecules. These molecules, dubbed fatty acid hydroxyl fatty acids, or FAHFAs, enhance insulin sensitivity and glucose control. Better yet, they also reduce inflammation.

Ordinarily, elevated fatty acids are associated with insulin resistance and glucose intolerance, which in turn are associated with diabetes and metabolic disease. Yet elevated FAHFAs have been found to account for enhanced insulin sensitivity and improved glucose control in a specially engineered mouse strain. FAHFAs thus join a small collection of beneficial fatty acids alongside the omega-3 fatty acids.

Unlike the omega-3 fatty acids, which are found in fish oil, the FAHFAs are made in mammals. In fact, they are found in fat cells as well as other cells throughout the human body. FAHFA levels can even be detected in the blood.

All of these facts auger well for therapeutic development, say the researchers who discovered the FAHFAs. These researchers were led by Barbara Kahn, M.D., vice chair of the Department of Medicine at the Beth Israel Deaconess Medical Center (BIDMC) and the George R. Minot Professor of Medicine at Harvard Medical School, and Alan Saghatelian, Ph.D., a professor in the Clayton Foundation Laboratories for Peptide Biology at the Salk Institute.

“FAHFAs [are advantaged] in terms of therapeutic development because we can potentially modify the rate of production and breakdown throughout the body,” said Dr. Kahn. “Because we can measure FAHFA levels in blood, low levels may turn out to be an early marker for the risk of developing type 2 diabetes. Consequently, if restoring FAHFA levels in insulin resistant individuals proves to be therapeutic, we may potentially be able to intervene before the development of frank diabetes.”

“These lipids are amazing because they can also reduce inflammation, suggesting that we might discover opportunities for these molecules in inflammatory diseases, such as Crohn’s disease and rheumatoid arthritis, as well as diabetes,” added Dr. Saghatelian.

The scientists presented their finding October 9 in the journal Cell, in an article entitled “Discovery of a Class of Endogenous Mammalian Lipids with Anti-Diabetic and Anti-Inflammatory Effects.”

“Mice overexpressing the Glut4 glucose transporter in adipocytes have elevated lipogenesis and increased glucose tolerance despite being obese with elevated circulating fatty acids,” wrote the authors. “Lipidomic analysis of adipose tissue revealed the existence of branched fatty acid esters of hydroxyl fatty acids (FAHFAs) that were elevated 16- to 18-fold in these mice.”

The lipidomic analysis relied on mass spectrometry technology to quantify hundreds of lipids from biological samples. Four of these lipids turned out to be of particular interest because they were elevated in the engineered mice but not in normal mice. Although they could not be found in the existing databases the scientists consulted, their structures were ultimately elucidated via tandem mass spectrometry (MS/MS) and confirmed via chemical synthesis.

Molecules in the FAHFA family, the researchers found, consist of a hydroxyl fatty acid and another fatty acid that are joined by an ester bond: “FAHFA isomers differ by the branched ester position on the hydroxy fatty acid (e.g., palmitic-acid-9-hydroxy-stearic-acid, 9-PAHSA).”

Additional experiments revealed that feeding the mice extra FAHFAs resulted in a rapid and dramatic drop in blood sugar and rise in insulin. They also looked at FAHFA levels in human fat and plasma, studying samples from individuals who were known to be insulin resistant and at high risk for developing diabetes. In this case, FAHFA levels were found to be 50–75% lower than levels in people with normal insulin sensitivity, suggesting that changes in FAHFA levels might be contributing to diabetes.

The researchers also identified GPR-120, the cellular receptor that FAHFAs bind to. “When FAHFAs bind to GPR-120, they are able to control how much glucose is taken up into fat cells,” explained Dr. Kahn. The receptor may also be responsible for the effects of the novel lipids to reduce widespread macrophage activation, which is associated with obesity and with inflammatory diseases.

“The discovery of FAHFAs provides important new insights underlying metabolic and inflammatory diseases, and offers viable new treatment avenues that we hope to be able to test in clinical trials,” emphasized Dr. Kahn. “This is of critical importance as rates of obesity and type 2 diabetes remain at epidemic proportions worldwide.”

Thursday, October 09, 2014

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Roche has picked up exclusive rights to AbVitro's primer extension-based target enrichment (PETE) technology and associated patent applications AbVitro has filed. The technology, Roche says, will be used to support next-generation sequencing (NGS) directly from blood or other biological samples—something that could be a boon for clinicians.

Roche plans to incorporate PETE technology into its Sequencing Unit R&D pipeline to support the strategy of providing a full NGS workflow solution for clinical sequencing. Per the agreement, scientists from both firms will be teaming up to develop the technology.

"Sequencing is transforming the understanding among researchers and clinicians of how genomics will impact health," Dan Zabrowski, head of Roche Tissue Diagnostics and the Sequencing Unit, said in a statement. "We look forward to advancing this technology in order to streamline sequencing methods for easy-to-use clinical applications."

Therapeutic target discovery company AbVitro has a technology platform that the firm says can leverage natural immune responses to address diseases with unmet medical needs. This platform was based on technology developed by George Church, Ph.D., at Harvard Medical School.

"It is wonderful to see another potentially transformative sequencing technology transition into Roche where it can impact our daily lives," Dr. Church commented.

Enal Razvi, Ph.D.

Wednesday, October 08, 2014

As omics technologies continue to migrate toward clinical applications, a market involving prognostic and predictive biomarkers is growing rapidly. This is an important space as it represents the segregation of biomarkers into classes based on their clinical utility. Biomarkers will be fundamental to the success of targeted therapeutics in the future.

The implementation of personalized medicine in oncology and beyond requires a precise understanding of disease progression as well as molecular targeting of therapies to interrogate molecular lesions. Prognostic and predictive biomarkers have the power to affect these two functions, respectively. Indeed, many putative biomarkers have been postulated in the literature, but few have successfully been utilized in the clinic. If personalized medicine is to expand and scale across therapeutic classes, biomarkers must proliferate and find clinical utility.

For the rest of the story, click here.

Yan Zhang, Ph.D., and Joyce Peng, Ph.D.

Wednesday, October 08, 2014

Figure 1. Method of sequencing samples from a JAK2-negative myeloproliferative neoplasm patient

As one of the most prevalent causes of death across the globe, the burden of cancer is still sharply increasing, predominantly due to the aging population. As such, the current focus of many researchers is on how to accurately diagnose and treat various cancer types. However, human cancers usually carry several different genomic variations, such as copy number variations and point mutations, which essentially lead to tumor heterogeneity. These tumors therefore display different cellular morphology, gene expression, metabolism, motility, proliferation, and metastatic potential. This phenomenon occurs both within individual tumors and between different tumors in the body.

This inherent variation of cancer cells causes significant issues in the development of targeted therapies. Drug development has previously focused on the genomic differences between complex mixtures of cells, employing techniques that may obscure the heterogeneity of single cells, leading to the development of less efficient treatments.

For the rest of the story, click here.

Caroline Meade and Natasha F. Bonhomme

Wednesday, October 08, 2014

Experts have suggested that in the next decade large-scale sequencing for all healthy babies at birth is plausible. [Source: © Miroslav Beneda - Fotolia.com]

Since 1963, state public health programs have screened newborns for a number of life-altering health conditions. Many of these disorders are rare and genetic, and if caught in the first weeks of life they can be treated or managed to prevent death or a lifetime of disability. Early detection can also help families avoid the lengthy and stressful “diagnostic odyssey” involved in finding out what ails their child (Exe et al.). In 2013, the United States celebrated the 50th anniversary of newborn screening. From scientist Robert Guthrie’s discovery of a test for phenylketonuria to development of state programs that screen every newborn for up to 56 conditions, newborn screening has saved and improved millions of lives. The state-mandated screening gives newborns their best chance for typical development, in large part because of strong national guidelines and efficient state public health systems that have been evolving to support screening for the last 50 years.

As newborn screening success stories gained national notoriety in the early 1960s, scientists quickly discovered diagnostic tests for a host of genetic disorders that could be treated at birth. State public health officials then responded by developing mandatory screening programs with inclusion of increasing numbers of genetic and metabolic conditions. While testing every newborn at birth is a seemingly simple process, organizing the resources required for obtaining samples, analyzing results, diagnosing disorders, and providing follow-up care is a large undertaking for state public health systems.

For the rest of the story, click here.

Alex Philippidis

Wednesday, October 08, 2014

Pharmacovigilance encompasses clinical care optimization, a big data model for efficient targeting of tests and treatments and vigilance for adverse events. [Source: Big Data]

Personalized medicine has long offered more hype than hope. But as genetic knowledge has multiplied in recent years, researchers—and more importantly, computing tools—have begun catching up with all that far-flung data, harnessing it into new databases and systems that offer the best prospects yet for delivering on the promise of precision treatments.

In several papers published this year for which he was corresponding author, Leo Anthony Celi, M.D., M.P.H., clinical research director for MIT’s Laboratory of Computational Physiology, joined David J. Stone, M.D., a visiting professor at University of Virginia and faculty associate at UVA Center for Wireless Health, and others in discussing the challenges that can be addressed with new computing systems, and the key data such systems must capture for clinicians.

In June, Drs. Celi and Stone joined Andrew J. Zimolzak, M.D., a research fellow at Children’s Hospital Boston, in proposing an operational vision for real-time incorporation of external health data through “dynamic clinical data mining” (DCDM), which they envision as driving next-generation electronic medical records (EMRs) as well as “turning medical practice into a data-driven, logical, and optimized system.”

For the rest of the story, click here.

Chris Anderson

Wednesday, October 08, 2014

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As the genomic age takes hold, the medical and pharmaceutical industries are just now beginning to scratch the surface of innovation in testing for a wide range of diseases, as well as creating highly targeted therapies based on an individual’s genetic makeup. But as clinicians embrace the great promise of personalized and precision medicine, the explosion of new genetic data is raising often hard-to-answer ethical questions. How should this information be used? How should it be protected? To whom should it be disclosed?

While the government has stepped in with legal protections—most notably the Genetic Information Nondiscrimination Act (GINA)—the scope of these laws don’t have much relevance to clinicians or researchers. In the case of GINA, its protections are largely designed to protect people from being denied health insurance or from discrimination in the workplace based on their genetic information. As a result, policies for the handling of healthcare information are often based on advisory positions of professional societies or formulated on a case-by-case basis.

For the rest of the story, click here.

Wednesday, October 08, 2014

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

Clinical OMICs Issue 11

Wednesday, October 08, 2014

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CRO med fusion is partnering with genomics technology and services provider GenomOncology to optimize treatment strategies based on the patient's disease state and tumor profile by integrating GenomOncology's technology platform—the GO Clinical Workbench™—and support services with med fusion's soon-to-be expanded solid tumor disease-specific panels. This pairing, the firms say, would offer researchers a comprehensive lab report detailing relevant drug and clinical trial options.

med fusion expects the expansion of its solid tumor menu to come out in the early third quarter of this year with the launch of disease-specific panels including NSCLC (non-small-cell lung cancer) and CRC (colorectal cancer). The expanded menu, the CRO says, is powered in part by next-generation sequencing (NGS) technology that med fusion validated this summer.

GenomOncology says its GO Clinical Workbench can streamline the use of NGS data in conjunction with other analytic modalities, simplify the creation of a summary report, and provide a traceable workflow and rules-based decision support for the clinical interpretation of genomic data. The platform can be configured to each clinical laboratory's specific needs with systems integration (LIMS, EMR, etc.), setting of quality control and annotation parameters, and design of the resultant clinical report.

"Genomics-based precision medicine requires the clinical interpretation of genomic data—streamlined use of next-generation sequencing information in conjunction with other analytic modalities—as well as rules-based decision support," Manuel Glynias, president and CEO of GenomOncology, said in a statement. "The availability of an expert knowledge base like My Cancer Genome, exclusively integrated with the GO Clinical Workbench, provides a clinical report that educates physicians and gives them confidence as they make treatment decisions for patients."

Tuesday, October 07, 2014

Benjamin Darbro, M.D., Ph.D., leader of the winning team.

A project team led by Benjamin Darbro, M.D., Ph.D., director of the Shivanand R. Patil Cytogenetics and Molecular Laboratory at the University of Iowa Hospital and Clinics, has won the inaugural Appistry Pipeline Challenge for developing and executing a pipeline designed to reduce the costs and turnaround times associated with next-generation sequencing (NGS)-based genomics testing. The team has won a complete hardware and software system from Appistry valued at approximately $70,000.

The winning pipeline, Appistry says, will integrate the results of a concurrently run NGS assay and a SNP-containing chromosomal microarray (CMA) to calculate patient specific, genome-wide, NGS-performance metrics (e.g., sensitivity, specificity, positive and negative predictive value) for different types of genetic variations detectable by the CMA platform—performance metrics intended to alleviate the need for confirmatory assays using conventional Sanger sequencing.

Appistry adds that the proposed pipeline will leverage NGS analysis tools provided by the firm—specifically the Genome Analysis Toolkit—along with other tools and a tool developed by the Cytogenetics and Molecular Laboratory called CNV-ROC. The Appistry tools are included as part of Appistry’s Ayrris On Ramp Program for NGS Analysis, a program that includes a developer workstation that can process 200 gigabases per day, Ayrris® software for developing and executing NGS pipelines, and preconfigured analysis tools and starter pipelines. The company is also providing Dr. Darbro a MacBook Air or iPad Air to help facilitate his personal research.

Rich Mazzarella, Ph.D., Appistry CSO and chair of the judging panel for the Pipeline Challenge, said in a statement that the firm’s goal in sponsoring the challenge was to inspire and support innovation that could advance the utility and impact of NGS in clinical labs. “There is enormous promise in the pipeline proposed by Dr. Darbro, and we look forward to assisting in its development over the coming year,” he added.

Friday, October 03, 2014

Sigma-Aldrich says the deal will grow its antibody portfolio and better serve IHC customers. [© Sebastian Kaulitzki - Fotolia.com]

Eleven days after agreeing to be acquired by Merck KGaA for $17 billion, Sigma-Aldrich signaled that it intends to continue growing its presence in diagnostics with clinical applications, saying today it agreed to acquire Cell Marque for an undisclosed price.

Sigma-Aldrich said the deal was intended to strengthen its antibody portfolio and better serve immunohistochemistry (IHC) customers.

The deal—anticipated to close by the end of this year—is subject to regulatory approvals and other customary closing conditions.

Headquartered in Rocklin, CA, Cell Marque employs 90 people and focuses on designing, developing, and manufacturing antibody reagents and kits—including validated, fit-for-purpose antibodies and IHC staining kits aimed at pathologists and clinicians focused on patient management.

“We expect that Cell Marque's strong in vitro diagnostic (IVD) antibody product lines and solid relationships with pathologists and companies that provide automated staining instrumentation will broaden the diagnostic health reach of Sigma-Aldrich," Frank Wicks, Ph.D., president of Sigma-Aldrich's Applied Business Unit, said in a statement.

Sigma-Aldrich said Cell Marque’s will complement its IHC product family, as well as existing workflow solutions for IVD customers. Sigma already manufactures and distributes 230,000 chemicals, biochemicals and other essential products to more than 1.4 million customers globally in research and applied labs as well as in industrial and commercial markets.

Sigma-Aldrich’s offerings would be added to the 60,000 products and solutions now marketed by Merck KGaA’s Merck Millipore unit under their deal, announced Sept. 22. The companies have said the combination will enable Merck Millipore to increase its presence in North America—and perhaps more importantly, add a presence in Asia as R&D and manufacturing continue to expand worldwide.

A key tool for expansion would be continued growth of what is now Sigma-Aldrich’s eCommerce platform, which offers 24-hour delivery in major markets.

Sigma-Aldrich said it expects the Cell Marque acquisition to be “neutral to mildly accretive” to its earnings per share next year. 

Alex Philippidis

Tuesday, September 30, 2014

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The FDA today issued draft guidance detailing its plans for regulating laboratory-developed tests (LDTs) that it deems as “high-risk” along the lines of Class III medical devices—setting up a showdown with academic medical centers and other developers of the tests, which have opposed efforts at imposing new rules.

In a few days, the agency said, it will launch a 120-day public comment period that will begin with publication of a formal notice of the release of the draft guidances in the Federal Register. Released by the FDA today were two draft guidance documents: Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs); and FDA Notification and Medical Device Reporting for Laboratory Developed Tests (LDTs).

The FDA has historically exercised only enforcement discretion over LDTs designed and used within a single laboratory, and had not sought to regulate their entry to market as is now required for Class III medical devices.

FDA Commissioner Margaret A. Hamburg, M.D., and other agency officials have sought to justify the new rules by saying that today’s LDTs differ from those that were around in 1976 when current rules took effect.

Unlike then, the agency contended in the draft guidances, many of today’s LDTs are much more complex, made with components not legally marketed for clinical use; used beyond local populations; manufactured in high volume; used widely to screen for common diseases rather than rare ones; and used for directing critical treatment decisions such as prediction of drug response.

“There is a wide range of risks associated with the wide variety of LDTs. Thus, FDA believes that a risk-based approach to regulatory oversight of LDTs is appropriate and necessary to protect patient safety,” the FDA stated in its Framework draft guidance.

LDT developers maintain that the tests are “laboratory testing services” and not medical devices subject to the Food, Drug, and Cosmetic Act (FDCA). At present, labs certified under the Clinical Laboratory Improvement Amendments (CLIA) waiver program may develop and use their own diagnostic tests internally, without FDA oversight.

“Subjecting LDTs to FDA regulation would eliminate the very characteristics which make LDTs and the regulatory framework that presently govern them so vital: flexibility and nimbleness in their ability to respond to unmet needs,” Alan Mertz, president of the American Clinical Laboratory Association, said September 9 in written testimony to the U.S. House of Representatives Energy and Commerce Committee Subcommittee on Health. “FDA regulation of LDTs as medical devices would dramatically slow not only the initial premarket approval of new tests, but also improvements to existing tests, delaying access to new and improved diagnostic testing services for patients and clinicians.”

As detailed in July, the FDA said it plans to begin premarketing approval (PMA) review requirements within 12 months after a final guidance for the highest-risk devices and phase it in over four years for the remaining high-risk devices. The devices would stay on the market during FDA review.

The agency said its focus on “high-risk” devices will begin with LDTs that have the same intended use as a cleared or approved companion diagnostic, followed by LDTs with the same intended use as an FDA-approved Class III medical device, and some LDTs designed to determine the safety or efficacy of blood or blood products.

All other LDTs will be prioritized for review using a public process with expert advisory panels “as appropriate,” the FDA said. The agency promised to provide advanced notice on the timing of enforcement of the new rules to manufacturers whose LDTs fall into high- and moderate- risk categories.

The FDA also said it “intends to” publish priority lists for its review of high-risk LDTs within 24 months of a final guidance—with enforcement for the initial prioritized group beginning “no less than 12 months” after the list is announced—as well as publish a priority list for “moderate-risk” LDTs within four years.

For “moderate risk” LDTs, which would be deemed Class II medical devices, labs would have to begin registration, listing, and adverse-event reporting six months after a final guidance is set. PMA for these LDTs would begin five years after final guidance, and be phased in over four years. FDA said it intends to accredit and use third-party reviewers for premarket submissions “as appropriate.”

The FDA said it will hold a webinar on October 23 at 2:00 p.m. EDT, to address clarification questions on the proposed framework. Details on dialing in and viewing the slide presentation are available here.

LDTs introduced to market on the date of publication of the final guidance, and for six months afterward, will be subject to FDA enforcement discretion as is now the case.

Satish Birudukota

Wednesday, September 24, 2014

The IVD market is segmented into clinical chemistry, immunology, hematology, coagulation, microbiology, molecular diagnostics, and other clinical instruments.

In vitro diagnostics (IVD) are a prominent and fast emerging segment of the global healthcare sector. IVD tests analyze human samples such as blood, urine, or tissue and provide information for making healthcare decisions. Key IVD tests include pregnancy test kits, blood glucose tests, laboratory tests for infectious disease, regular blood tests for cholesterol and hemoglobin content, genetic tests for various genetic diseases, etc.

Interest in companion diagnostics is also growing as providers and patients embrace the idea of selecting the best therapy for a particular patient based on their disease-related gene sequence.

IVDs have potential in prevention and early detection resulting in reduced treatment, enhanced therapy success, higher survival rates, and improved quality of life.

For the rest of the story, click here.

Tri Doan

Wednesday, September 24, 2014

Figure 1. Overview of the bioinformatics steps for NGS sequencing data, with the steps that SureCall software performs boxed in green.

While sequencing entire human genomes is an important achievement of next-generation sequencing (NGS) technology, many clinical research goals can be achieved by sequencing a subset of the genome or genes of interest. Targeted sequencing pools large numbers of individual samples to sequence at the same time. This approach lowers the total cost per sample, reduces turnaround time, and produces a more manageable dataset. However, analyzing NGS data requires computational resources and bioinformatics expertise that are a major bottleneck in terms of cost and time, particularly for investigators who want to manage their own experiments.

Agilent has developed an investigator-tailored NGS data analysis tool, called SureCall, that allows clinical researchers who use targeted sequencing panels for inherited diseases, cancer, and other areas to analyze, visualize, and contextualize NGS data using a single application and without need for coding or special hardware (Figure 1).

For the rest of the story, click here.

Gail Dutton

Wednesday, September 24, 2014

CombiMatrix, a specialist in cytogenomics, offers a microarray platform that is designed to conduct miscarriage analysis (which may include clarification of recurrence risks), prenatal analysis, and pediatric analysis.

CombiMatrix, a CLIA-certified laboratory, is bringing microarray analysis to the underserved problem of recurrent pregnancy loss as well as to prenatal testing. CombiMatrix performs microarray assays that deliver more complete results faster than traditional lab tests.

“Between 50% and 60% of all recurrent miscarriages are caused by a chromosomal abnormality,” Mark McDonough, president and CEO, says. To determine whether a chromosomal abnormality such as triploidy is present, tissue collected from a D&C procedure traditionally is sent to a lab for karyotyping, the standard-of-care genetic test.

“The problem is that it can take up to three weeks to get a result with karyotyping, and this technology returns results only 40% to 50% of the time,” McDonough notes. “Microarray-based cytogenic testing, like CombiSNP™, offers results in one week with 95% yield rates.”

For the rest of the story, click here.

Summer E. Allen, Ph.D.

Wednesday, September 24, 2014

Researchers at Keele University have developed SIFT-MS, or selected ion flow tube mass spectrometry, a real-time technique that measures volatile compounds exhaled by patients. SIFT-MS has been used to detect compounds associated with lung cancer, bacterial and fungal infections, and inflammatory bowel disease.

Clinical applications for mass spectrometry technology have exploded in recent years. Mass spectrometry analysis is often faster, cheaper, and more sensitive than other methods and is thus ideally suited for both diagnostics and therapeutic monitoring.

“Mass spectrometry is finally being accepted by microbiologists as a powerful analytical tool and is currently revolutionizing diagnostics,” says Haroun Shah, Ph.D., head of the proteomics research unit for Public Health England. “I think if you visit the smallest hospital laboratory in the U.K. today, you will find the technique either being used or being considered.”

Dr. Shah helped design the first dedicated linear matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) instrument used for clinical microbiology in 2000. In addition, he co-developed the mass spectrometry methods that are now used by clinical laboratories and biotechnology companies such as Bruker and bioMerieux.

For the rest of the story, click here.

John Russell

Wednesday, September 24, 2014

Using frozen tissue remains the method of choice for characterizing the genome, transcriptome, and proteome. But frozen biospecimens, such as those stored in the freezer-boxed cryovials shown here, are neither foolproof nor economical. Room temperature alternatives, say researchers at the University of California, Los Angeles, may be more sustainable.

Biobanking, already a critical resource for bioresearch and medicine, is becoming even more important. According to a forecast prepared by BCC Research, biobanking will represent a $183 billion worldwide market by 2015. Besides rising in value, biobanking is growing more complicated. Questions of science, ethics, administration, and business viability are all part of biobanking’s dynamic landscape. Multiple stakeholders including government, academia, industry, and patients are shaping the field’s policy and practices.

All this ferment suggests that it is an opportune time to review the state of biobanking and identify emerging trends. Accordingly, many biobanking experts are planning to gather at the sixth annual Leaders in Biobanking Congress. This CHI event is scheduled to take place September 15–17 in Seattle.

The event will cover both the business and the science of biobanking, prompting discussion of myriad topics.

For the rest of the story, click here.

Wednesday, September 24, 2014

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

Monday, September 22, 2014

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.”

Friday, September 19, 2014

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Thermo Fisher Scientific completed the listing of its Ion PGM Dx next-generation sequencing (NGS) system with the FDA for clinical use as a class II medical device.

Intended for targeted sequencing of human genomic DNA using peripheral whole-blood samples, the system supports the development and implementation of user-defined NGS diagnostic assays in a clinical laboratory and enables 21 CFR Part 11 compliance, according to Mark Stevenson, president of life science solutions at Thermo Fisher Scientific. The system was validated using a large control panel that contains an extensive number of germline variants that are representative of a range of human conditions, he continued, adding that when it is used for diagnostic assay development, customers may define, validate, lock, and publish protocols in a role-based workflow for implementation into routine use, from library construction to variant calling.

“Next-generation sequencing is rapidly becoming an indispensable tool for clinical laboratories around the world, allowing clinical professionals to simultaneously screen hundreds of genes from patient samples to provide key genetic information and enable patient enrollment within clinical trials,” said Stevenson. “The Ion Torrent platform and accompanying reagents provide a number of unique advantages to clinical customers, enabling accurate and reliable genetic variant analysis from more samples due to low DNA input requirements (10 ng) and faster turnaround times that reduce the time of sample to result.”

Thursday, September 18, 2014

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Researchers at Northwestern Medicine say they have developed the first blood test to diagnose major depression in adults. The assay, which works by measuring the levels of nine RNA blood markers, also predicts who will benefit from cognitive behavioral therapy based on the behavior of some of the markers.

In addition, the test showed the biological effects of cognitive behavioral therapy, the first measurable, blood-based evidence of the therapy's success. The levels of markers changed in patients who had the therapy for 18 weeks and were no longer depressed. 

"Blood transcript levels of nine markers of ADCY3, DGKA, FAM46A, IGSF4A/CADM1, KIAA1539, MARCKS, PSME1, RAPH1, and TLR7, differed significantly between participants with MDD [major depressive disorder] (N=32) and ND [nondepressed] controls (N=32) at baseline (q< 0.05)," wrote the investigators in their study (“Blood transcriptomic biomarkers in adult primary care patients with major depressive disorder undergoing cognitive behavioral therapy”) published in Translational Psychiatry. "Abundance of the DGKA, KIAA1539, and RAPH1 transcripts remained significantly different between subjects with MDD and ND controls even after post-CBT [cognitive behavioral therapy] remission (defined as PHQ-9 <5)."

"This clearly indicates that you can have a blood-based lab test for depression, providing a scientific diagnosis in the same way someone is diagnosed with high blood pressure or high cholesterol," said Eva Redei, Ph.D., who developed the test and is a professor of psychiatry and behavioral sciences at the Northwestern University Feinberg School of Medicine. "This test brings mental health diagnosis into the 21st century and offers the first personalized medicine approach to people suffering from depression."

Dr. Redei, who is co-lead author of the study, previously developed a blood test that diagnosed depression in adolescents. Most of the markers she identified in the adult depression panel are different from those in depressed adolescents.

The current method of diagnosing depression is subjective and based on nonspecific symptoms such as poor mood, fatigue, and change in appetite, all of which can apply to a large number of mental or physical problems. A diagnosis also relies on the patient's ability to report his symptoms and the physician's ability to interpret them. But depressed patients frequently underreport or inadequately describe their symptoms.

"Mental health has been where medicine was 100 years ago when physicians diagnosed illnesses or disorders based on symptoms," said co-lead author David Mohr, Ph.D., a professor of preventive medicine and director of the Center for Behavioral Intervention Technologies at Feinberg. "This study brings us much closer to having laboratory tests that can be used in diagnosis and treatment selection."

The new blood test will allow physicians for the first time to use lab tests to determine what treatments will be most useful for individual patients.

Major depressive disorder affects 6.7 percent of the U.S. adult population in a year, a number that is rising. There is a two- to 40-month delay in diagnosis, and the longer the delay, the more difficult it is to treat depression. An estimated 12.5 percent of patients in primary care have major depression but only about half of those cases are diagnosed. A biologically based test has the potential to provide a more timely and accurate diagnosis.

Caroline Meade and Natasha F. Bonhomme

Friday, September 12, 2014

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.

Wednesday, September 10, 2014

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

Clinical OMICs Issue 9

Shelly Gunn, M.D., Ph.D.

Wednesday, September 10, 2014

Single-gene testing just isn't adequate anymore, especially with the growing number of targeted therapies. Yet many physicians turn to large gene panels only as a last resort. [© khz—iStock]

There are huge benefits to genomic tumor assessment, both for better treatment now, and later, if first-line treatments fail. But I don’t think many cancer patients—and even some physicians—fully understand how important tumor sequencing can be to successful cancer treatment. Yet.

This is not surprising. Outside of a few tests for breast cancer, we really didn’t have the tools to do this sequencing even just five years ago. The first major breakthrough that I saw in clinical practice was for metastatic melanoma, a very rare clinical scenario where the incidence is maybe 10,000 cases a year. Suddenly in August 2011, there was a machine I could put in my lab, and in one day obtain results of a molecular test that had a tremendous impact on treating the patient, according to whether the tumor was BRAF positive or BRAF negative.

From that time on, there has been an increasing number of solid tumors where we can test for a genetic biomarker that indicates a specifically targeted treatment, such as the FDA-approved testing for EGFR in non-small-cell lung cancer and KRAS in colorectal cancer.

Single gene testing just isn’t adequate anymore, especially with the growing numbers of targeted therapies, both currently FDA-approved and in the pipeline. If a lung tumor isn’t being driven by EGFR, then you immediately want to know whether ALK is involved, and if not ALK then what about ROS, MET, PIK3CA, and etc. We need to be looking at multiple genes during our diagnostic testing, not just a few select biomarkers.

For the rest of the story, click here.

Jeffrey N. Gibbs

Wednesday, September 10, 2014

With the issuance of this new framework, the debate over FDA regulation of LDTs is now going to be held in full public view. [© Alexander Raths - Fotolia.com]

In 1992, the Food and Drug Administration (FDA) first stated that it had authority to regulate laboratory-developed tests. On July 31, FDA took its biggest step toward invoking this asserted authority by unveiling its “Framework for Regulatory Oversight of Laboratory-Developed Tests (LDTs).”

In the framework, FDA explains that while it had traditionally exercised enforcement discretion and not regulated LDTs, due to changes in the role and type of LDTs, the agency now intends to regulate LDTs as devices. The agency plans to do this in stages, phased in over a lengthy period of time.

For the rest of the story, click here.

Robin Munro

Wednesday, September 10, 2014

To make better use of genomics data, researchers need to make sure that they are gathering and sharing good quality clinical data as well. [© millaf – Fotolia.com]

It was inspiring to listen to Howard J. Jacob, Ph.D., professor of physiology and human and molecular genetics at Medical College of Wisconsin, speaking a few years back about successfully treating a young boy with an extreme form of inflammatory bowel disease using genome sequencing. It just shows that with the right time, the right data analytics, and expertisze there can be success in bringing genomics to the bedside.

So what needs to happen in genomic medicine to make this exceptional case become more common place? Now, almost four years later, the ambition and vision is there but major challenges still lie ahead.

For the rest of the story, click here.

Chris Anderson

Wednesday, September 10, 2014

According to Combimatrix, noninvasive screens play an important role in prenatal care, but should only be considered a first step.

Prenatal screening for Down syndrome first became available for expectant mothers with the advent, in the late 1960s, of a diagnostic test employing amniocentesis and fetal karyotyping. At the time, only one risk factor was considered—the age of the mother.

In the ensuing years, discoveries showing the correlation between over- and under-expression of specific biomarkers in the mother’s blood, such as alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), estriol, and inhibin A, led to new prenatal screening tests that could indicate the likelihood of not only Down syndrome but other potential birth defects.

While these tests are still widely used and continue to serve a valuable function in helping physicians screen high-risk patients for potential abnormalities, these screening tools also have a relatively high incidence of false positives and false negatives. Women with a normal pregnancy are often referred for unnecessary invasive procedures such as amniocentesis or chorionic villus sampling, both of which carry a risk of miscarriage.

For the rest of the story, click here.


Wednesday, September 10, 2014

University of Illinois researchers developed a cradle and app for the iPhone to make a handheld biosensor that uses the phone's own camera and processing power. [Brian T. Cunningham]

If you had to pick the most compelling mHealth, or mobile health, application, you might well pick mDiagnostics—the ability to perform laboratory work outside the laboratory. mDiagnostics promises to bring on-the-spot testing to poor and remote areas where conventional tools such as microscopes, cytometers, and colorimeters are unavailable.

Mobile, off-the-grid diagnostic tools are best compact. But, beyond that, choices abound. mDiagnostic tools could be sleek, self-contained, standalone devices. Or they could be modular. For example, an mDiagnostic tool could consist of an add-on device plugged into a general-purpose platform, the smartphone.

For the rest of the story, click here.

Monday, September 08, 2014

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.

Monday, September 08, 2014

Source: © taraki - Fotolia.com

Four cancer research institutes have joined with Illumina to form a consortium that will recommend standards for applying next-generation sequencing to cancer tumors.

The new Actionable Genome Consortium (AGC) said it aims to help oncologists and pathologists determine the best therapeutic and testing strategies for improving patient outcomes. Joining Illumina as founding members of the consortium are Dana-Farber Cancer Institute, Fred Hutchinson Cancer Research Center, MD Anderson Cancer Center, and Memorial Sloan Kettering Cancer Center (MSK).

ACG has articulated its core purpose as creating a comprehensive description of genomic alterations that define individual patients' tumors, or “cancer actionable genome.” To that end, AGC said it has developed and will publish recommendations for:

  • Best practices for biopsy, sample storage and transport, and extraction;
  • Technical performance standards for DNA sequencing;
  • Standards for variant calling, annotation and interpretation;
  • Guidelines for the format and content of clinical reports.

"Widely available, standardized genomic testing of tumors can be the means by which precision oncology and therefore precision medicine begins to live up to its promise," Rick Klausner, M.D., former director of the National Cancer Institute and now Illumina’s SVP & CMO, said in a statement.

Illumina’s co-founding of ACG comes as the sequencing giant looks to grow its business with clinical practices, reflecting the migration of genomic technologies into clinical settings and its ongoing effort to broaden its customer base beyond NIH-funded customers in academia and government.

Illumina and its partners in ACG intend to standardize actionability standards that now vary from provider to provider, complicating efforts to clinically interpret genomic tests. Most patients lack access to multidisciplinary Tumor Boards along the lines of those at major cancer centers which define what constitutes an actionable event in a tumor.

ACG’s recommendations are expected to facilitate development of in vitro diagnostics, additional information to support regulatory oversight of genomic testing for cancer, and reimbursement for new diagnostics.

The consortium also said it plans to carry out research that will leverage the scientific, clinical and technical capabilities of its member institutions for new collaborative, cross-institutional projects to address “grand” challenges in molecular oncology.

"Patients will be more likely to receive the proper targeted course of therapy from the outset when the community oncologist is aware of standard molecular testing procedures and how to interpret these test results," added Charles Sawyers, M.D., chair of the Human Oncology and Pathogenesis Program at MSK and a Howard Hughes Medical Institute Investigator.

Friday, September 05, 2014

Laboratory Corporation of America® Holdings (LabCorp) launched a new business, Enlighten Health Genomics, that builds on the diagnostic potential of next-generation sequencing (NGS) technology. The company said it aims to make genetic profiles a routine part of clinical decisions.

Enlighten Health Genomics combines LabCorp’s infrastructure and capabilities with a team of accomplished geneticists to offer diagnostic capabilities, NGS analysis and interpretation, and informed genetic counseling.

Later this year, Enlighten Health Genomics said it will introduce ExomeReveal, a whole exome sequencing testing service. ExomeReveal can provide genome-wide interpretation for children with serious childhood genetic diseases as well as additional diagnostic information for patients of any age.

“We believe that patients with serious genetic conditions require a thorough interpretation of their genome,” said David Goldstein, genetics professor at Duke University, who will chair Enlighten Health Genomics’ scientific advisory board. “Our goal is to offer innovative and affordable diagnostic solutions to broad patient populations, making genomics a routine part of clinical decisions.”

“Enlighten Health Genomics is an important part of LabCorp’s strategy to capitalize on our unique assets, create new sources of revenue from our core capabilities and meaningfully differentiate us from competitors,” said David P. King, chairman and CEO at LabCorp. “The launch of this business is another tangible step in the development of Enlighten Health, our initiative to create innovative tools and capabilities to enhance patient care.”

Friday, September 05, 2014

Veracyte is planning to launch Allegro's lead lung cancer test in the second half of 2015. [Elnur - Fotolia.com]

Molecular cytology diagnostics firm Veracyte is acquiring Massachusetts-based company Allegro Diagnostics for $21 million—$7.8 million in cash, $13.2 million in Veracyte common stock. Allegro's primary focus is on developing diagnostic tests for lung cancer, and Veracyte plans to launch Allegro's lead lung cancer test in the second half of 2015.

Allegro say its lung cancer test can help physicians determine which patients with lung nodules who have had a nondiagnostic bronchoscopy result are at low risk for cancer and thus do not need invasive procedures. The gene expression test uses a "field of injury" genomic technology platform that allows for the testing of cytology samples obtained through bronchoscopy rather than surgery. The technology can, according to the firm, detect molecular changes that occur throughout the respiratory airways in response to smoking and that are correlated with disease. 

Veracyte's president and CEO Bonnie H. Anderson said in a statement that this acquisition will allow the firm to enter the pulmonology market. "Allegro is a natural fit for us and we believe this move further establishes our leadership in molecular cytology, using genomics to resolve diagnostic ambiguity preoperatively and thus spare patients from unnecessary invasive procedures and reduce associated healthcare costs," she added.

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

Thursday, September 04, 2014

Over 12,000 publications in the POC space from 110 countries were analyzed for this report. [© Anetta - Fotolia.com]

Our goal for this analysis was to understand the landscape of point-of-care (POC) diagnostics, and we believe that an excellent methodology to apply is to analyze the en bloc set of publications in this space.


  • The POC diagnostics field is a global growing space.
  • We have characterized the landscape via a bottom-up analysis of the entire publications ensemble.
  • Specific technologies such as segments of PCR are growing rapidly in this field—testifying to the central role nucleic acid analytes are occupying in POC.
  • There is small overlap with molecular diagnostics, suggesting that the POC field is an independent self-standing entity with significant growth potential.

Click here to download the PDF report.

Wednesday, August 27, 2014

Source: © deanm1974 - Fotolia.com

The National Institutes of Health has issued a final NIH Genomic Data Sharing (GDS) policy to promote data sharing as a way to speed the translation of data into knowledge, products, and procedures that improve health while protecting the privacy of research participants. The final policy was posted in the Federal Register August 26, 2014, and published in the NIH Guide for Grants and Contracts August 27, 2014.

Starting with funding applications submitted for a January 25, 2015, receipt date, the policy will apply to all NIH-funded large-scale human and nonhuman projects that generate genomic data, including research conducted with the support of NIH grants and contracts and within the NIH Intramural Research Program.

A report on genomic data sharing through the NIH database for Genotypes and Phenotypes (dbGaP) appears in the August 27, 2014, advance online issue of Nature Genetics.

"Everyone is eager to see the incredible deluge of molecular discoveries about disease translated into prevention, diagnostics, and therapeutics for patients," said Kathy Hudson, Ph.D., NIH deputy director for science, outreach, and policy. "The collective knowledge achieved through data sharing benefits researchers and patients alike, but it must be done carefully. The GDS policy outlines the responsibilities of investigators and institutions that are using the data and also encourages researchers to get consent from participants for future unspecified use of their genomic data."

Along with statistics about the use of dbGaP data, the Nature Genetics report outlines the challenges facing the field, such as the increased volume and complexity of genomic data.

"Advances in DNA sequencing technologies have enabled NIH to conduct and fund research that generates ever-greater volumes of GWAS [genome wide association studies] and other types of genomic data," noted Eric Green, M.D., Ph.D., NHGRI director, report co-author and a co-chair of the trans-NIH committee that developed the GDS policy. "Access to these data through dbGaP and according to the data management practices laid out in the policy allows researchers to accelerate research by combining and comparing large and information-rich datasets."

A key tenet of the GDS policy is the expectation that researchers obtain the informed consent of study participants for the potential future use of their de-identified data for research and for broad sharing. NIH also has similar expectations for studies that involve the use of de-identified cell lines or clinical specimens.

The two-tiered system for providing access to human data is based on data sensitivity and privacy concerns developed under the GWAS policy will continue. For controlled-access data, investigators will be expected to use data only for the approved research, protect data confidentiality (including not sharing the data with unauthorized people), and acknowledge data-submitting investigators in presentations and publications.

NIH officials say they expect any institution submitting data to certify that the data were collected in a legal and ethically appropriate manner and that personal identifiers, such as name or address, have been removed. The NIH GDS policy also expects investigators and their institutions to provide basic plans for following the GDS policy as part of funding proposals and applications.

The NIH GDS governance structure, described at http://gds.nih.gov/04po2.html, will be responsible for oversight of the GDS policy, including policy needs and issues related to data submission and access. The NIH advises investigators seeking funding to contact relevant extramural program directors or an NIH institute or center Genomic Program Administrator (GPA) as early as possible to discuss data sharing expectations and timelines that would apply to their proposed studies. For a list of GPAs, visit http://gds.nih.gov/04po2_2GPA.html.

Thursday, August 21, 2014

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.

Emil Salazar

Wednesday, August 13, 2014

There’s reason to be both optimistic and pessimistic about the United States IVD market, depending on what sectors one wishes to focus on.  Despite persistent challenges to the U.S. in vitro diagnostics (IVD) market, advanced testing segments can lead a bounce-back delivering growth to test innovators—suppliers and labs alike. Chief among recent disappointments in U.S. IVD market performance has been the disruption of histology and molecular markets, previous mainstays of high revenue growth. Recovery in the U.S. IVD market will depend in large part on the contributions of histology and molecular diagnostic testing segments, which are projected to grow by an average of 7.5% per year through 2018. Market expansion for these advanced diagnostics segments will be a result of test introduction and the stabilization of coverage and reimbursement decisions and procedures on the part of payers.

For the rest of the story, click here.

Alex Philippidis

Wednesday, August 13, 2014

The point-of-care testing market can expect significant growth, but cost and compliance challenges still exist. [© Photographee.eu - Fotolia.com]

Point-of-care testing (POCT) is among the fastest-growing areas of laboratory medicine, driven by clinicians’ increased need for technologies that are faster, cheaper, and provide more robust, clinically useful results than ever—a need fueled more recently by the ongoing restructuring of U.S. healthcare through the Affordable Care Act (ACA).

The POCT market is projected to grow to $27.5 billion by 2018 based on a compound annual growth rate of 9.3% since 2013 (MarketsandMarkets), which would peg the current market size at a little over $16 billion. Glucose tests remain the majority of the POCT market—53.7% in 2013 (Reportlinker.com)—but have fallen from 70% in 2011 (RnR Market Research), reflecting expanded use of POCT.

POCT is broad enough to take in the processing lab’s traditional molecular diagnostics increasingly seen in hospitals, home pregnancy or glucose tests, and “rapid diagnostic tests” or RDTs. “Rapid” can range from seconds to hours while patients wait, as long as it’s within a clinical encounter that allows for quick decision-making by the clinician.

For the rest of the story, click here.

Patricia Fitzpatrick Dimond, Ph.D.

Wednesday, August 13, 2014

The growth of genomic medicine has cast a spotlight on the need for higher-resolution technologies for chromosomal analysis. [© fotohunter/iStock]

Detection and analysis of structural variability within chromosomes have become an integral part of genomic medicine. Because genomic instability and chromosomal abnormalities characterize cancer as well as many developmental diseases, understanding these structural aberrations can provide insight into disease etiology, treatment options, and prognosis.

According to physicians, current cytogenetic tests for developmental diseases tests, including G-banded chromosome analysis and fluorescence in situ hybridization (FISH), provide useful information for both clinicians and families, allowing identification of potential medical interventions for the patients. This information, they say, also enables accurate recurrence-risk counseling and helps families plan for the expected natural history of the disease. 

For the rest of the story, click here.

Muin J. Khoury, M.D., Ph.D., and Scott Bowen

Wednesday, August 13, 2014

Each year millions of babies are routinely screened for certain genetic, endocrine, and metabolic disorders, often using a point-of-care test at the bedside. [© millaf – Fotolia.com]

Thirteen years after the completion of the Human Genome Project, an increasing number of genomic applications, including next-generation sequencing (NGS), are poised for clinical use. Fulfilling the promise of genomics to improve health in the real world requires a public health perspective.

As genomics reaches the bedside, a public health “post bedside” research agenda will be able to assess the contribution of genomics and other new markers to health and disease in the larger social and environmental context, evaluate promising genomic technologies for their potential to improve health and healthcare, design appropriate strategies for integrating genomics into clinical and public health practice and ensuring access, and continuously measure population health impact of these new technologies. 

For the rest of the story, click here.

Kate Marusina, Ph.D.

Wednesday, August 13, 2014

Exome sequencing has promise in oncology testing, particularly in the monitoring of disease progression and the prediction of therapeutics responses. To realize this promise, researchers are developing and validating assays of ever-wider scope. [© Zmeel /iStock]

Next-generation sequencing (NGS) not only continues to make steady advances in the molecular diagnosis of cancers, it also seems to fit perfectly with our current knowledge of the oncogenome. In particular, by making it possible to screen the entire coding sequence of cancer-related genes, NGS overcomes a key problem—cancer predisposition cannot be monitored by just a few hotspot mutations.

The sensitivity, speed, and potentially decreased cost per sample make NGS a highly attractive technology. In fact, NGS may soon consolidate many other platforms. While some NGS applications, such as whole-genome sequencing, will probably have to wait several years before they spread and enter routine clinical use, other NGS applications are ready now.

One NGS application that shows immediate promise for clinical oncology testing is exome sequencing. “We hope that in the near future, sequencing of the cancer exome will soon provide oncologists with information they need to identify and utilize treatment options based on the patient’s genomic profile,” says Helen Fernandes, Ph.D., associate professor of pathology and laboratory medicine, Weill Cornell Medical College. Dr. Fernandes, however, adds that NGS will become established in the clinic only after certain challenges are addressed.

For the rest of the story, click here.

Wednesday, August 13, 2014

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

Clinical OMICs Issue 8

Alex Philippidis

Wednesday, August 13, 2014

Cologuard is designed to analyze DNA alterations and blood in the stool to detect the presence of colon cancer and precancers. [Exact Sciences]

Exact Sciences has won FDA approval for the first noninvasive DNA screening test for colorectal cancer—the first stool-based diagnostic designed to indicate the presence of abnormal growths in red blood cells and DNA mutations, and the first test to be approved under a joint parallel review pilot program by the agency and the Centers for Medicare and Medicaid Services (CMS).

Cologuard® is designed to analyze both stool DNA and blood biomarkers, and is intended for at-home use by adults 50 years old and older. The test has been proven to find 92% of cancers and 69% of the most advanced precancerous polyps in average risk patients, according to Exact Sciences.

Upon FDA approval, Exact Sciences also received a proposed coverage memorandum from CMS under the pilot program, designed to help reduce the time between FDA approval and Medicare coverage by as many as six months. A final National Coverage Determination is expected to be posted in October or November of this year, following a public comment period.

Priced at $599, Cologuard is designed to detect biomarkers from cancer DNA that is shed from the colon as part of the digestive process and blood released in the stool. Through their physician, patients order a Cologuard kit mailed directly to their home. Patients then collect a stool sample via the Cologuard Collection Kit, then send the kit back to the Exact Sciences lab for testing through a pre–paid mailer.

The stool sample is analyzed in an automated system to yield a single test result—positive or negative for the presence of precancerous polyps or cancer. Results from the Cologuard test are turned around in about two weeks, with patients learning their results directly from their physician. Patients with positive test results are advised to undergo a diagnostic colonoscopy.

Cologuard does not require medication or dietary restrictions, or bowel preparation prior to taking the test.

“The test is designed for high accuracy, ease of patient use, and wide accessibility. We hope that it will make a difference and save many lives,” David Ahlquist, M.D., a Mayo Clinic gastroenterologist and co-inventor of the test, said in a statement.

Exact Sciences licenses the Cologuard technology from Mayo Clinic. Under that licensing agreement, Mayo and Dr. Ahlquist share in equity and royalties. Revenue received by Mayo Clinic is used to support its not–for–profit mission in patient care, education and research, the company said.

FDA said its approval of Cologuard does not change current practice guidelines for colorectal cancer screening. Stool DNA testing has yet to be recommended as a screening method for colorectal cancer by the U.S. Preventive Services Task Force (USPSTF). The task force still recommends that adults age 50 to 75, at average risk for colon cancer, be screened using fecal occult blood testing, sigmoidoscopy, or colonoscopy.

According to FDA, Cologuard’s safety and effectiveness were established through the Phase III DeeP–C Study, in which 10,023 subjects were screened. The clinical trial compared the performance of Cologuard to the commonly-used non-invasive fecal immunochemical test (FIT). Cologuard detected 92% of colorectal cancers and 42% of advanced adenomas in the study population, compared with 74% and 24%, respectively, through FIT screening. However, Cologuard gave an accurate negative screening for colorectal cancer or advanced adenomas less often -- 87% of study subjects, versus 95% via FIT.

Results from DeeP–C were published in April in the New England Journal of Medicine.

“Cologuard addresses a critical need for a more convenient screening option for patients to aid in prevention and early detection,” stated Kevin Conroy, the president, CEO and chairman of Exact Sciences. “Exact Sciences is committed to making Cologuard available and accessible to patients and looks forward to advancing cancer detection in other gastrointestinal cancers.”

CMS has proposed coverage for the Cologuard test once every three years for Medicare beneficiaries who are 50 to 85 years old; at average risk of developing colorectal cancer; and show no signs or symptoms of colorectal disease including but not limited to lower gastrointestinal pain, blood in stool, positive guaiac fecal occult blood test or fecal immunochemical test.

Exact Sciences said it plans to make Cologuard available in select countries in Europe pending CE Mark.

Kevin Mayer

Friday, August 08, 2014

A genomic analysis of tumors from 12 tissues of origin reveals a new classification system. It consists of 11 subtypes that appear to reflect the cell type of origin. [Zhong Chen, NIH/NIDCD]

Advancing the work of The Cancer Genome Atlas (TCGA), a large team of researchers from multiple institutions performed a comprehensive analysis of molecular data from thousands of patients representing 12 different types of cancer. The analysis pointed to an alternative system for classifying cancer. Instead of defining cancers according to their tissues of origin, the new system considers molecular subtypes.

When the new system is used, as many as 1 in 10 cancers may be reclassified. In these instances, reclassification may be anything but academic. It may, for example, suggest that cancers from a particular tissue may comprise cancers of different subtypes, each with a different prognosis, each vulnerable, possibly, to different therapies.

A new classification system for cancer could also affect drug development or the recruitment of patients into clinical trials.

The new system was presented August 7 in the journal Cell, in an article entitled “Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin.” This article described how tumors were characterized using six different platforms—mostly genomic platforms such as DNA and RNA sequencing, plus a protein expression analysis.

These platforms generated findings that converged on the same set of 11 molecular subtypes, giving the researchers confidence that the subtypes were valid, as well as suggesting that different kinds of data could be used to classify a particular tumor. Of these 11 subtypes, five were nearly identical to their tissue-of-origin counterparts. Several distinct cancer types, however, were found to converge into common subtypes. For example, lung squamous, head and neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes.

A striking example of the genetic differences within a single tissue type is breast cancer. The breast, a highly complex organ with multiple types of cells, gives rise to multiple types of breast cancer: luminal A; luminal B; HER2-enriched; and basal-like, which was previously known. In this analysis, the basal-like breast cancers looked more like ovarian cancer and cancers of a squamous-cell type origin, a type of cell that composes the lower-layer of a tissue, rather than other cancers that arise in the breast.

Study participants—which included researchers from the University of California, Santa Cruz, Buck Institute for Age Research, University of North Carolina Health Care, and University of California, San Francisco—relied on a method they called cluster-of-cluster assignments (COCA). The COCA subtypes, the researchers noted, could reflect tumors arising from distinct cell types.

“In this new taxonomy, cancers of nonepithelial origin (e.g., neural, muscle, connective tissue) appear most different from epithelial tumors based on virtually all molecular platforms,” wrote the researchers in Cell. “The next most marked difference is apparent between epithelial cancers arising from basal layer-like cells (C2-squamous-like and C4-BRCA/basal) and those with secretory functions (C1-LUAD-enriched and C3-BRCA/Luminal). Molecular commonalities within a COCA subtype suggest common oncogenic pathways.”

“We think the subtypes reflect primarily the cell of origin. Another factor is the nature of the genomic lesion, and third is the microenvironment of the cell and how surrounding cells influence it,” said Josh Stuart, Ph.D., one of the Cell study’s authors and a professor of biomolecular engineering at UC Santa Cruz. “We are disentangling the signals from these different factors so we can gauge each one for its prognostic power.”

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

Tuesday, August 05, 2014

The CVD space is an attractive segment wherein POC diagnostics finds significant utility. [© Alexander Raths - Fotolia.com]

The focus of this GEN Market & Tech Analysis report is to present some of our recent industry tracking of the point-of-care diagnostics (POCD) space.


  • We present the POC diagnostics space with emphasis upon cardiovascular disease (CVD) in this report.
  • The growth of the POC space is exponential and its impact on CVD cannot be ignored.
  • CVD is an optimal therapeutic area for POC diagnostics and in this report we present the reasons for this trend, and the associated biomarkers that are being deployed in POC tests.
  • The expanding POC space and its impact on many other therapeutic spaces is the driver for the market forecast, which predicts >30% growth of POC over the coming years.

Click here to download the PDF report.

Tuesday, August 05, 2014

Source: © fotoliaxrender - Fotolia.com

Scientists from McGill University and the Génome Québec Innovation Centre say they have achieved a technical advance that could result in speedier diagnosis of cancer and various prenatal conditions. Their discovery, which is described online (“Convex lens-induced nanoscale templating”) in the Proceedings of the National Academy of Sciences (PNAS), lies in a new tool developed by Sabrina Leslie, Ph.D., and Walter Reisner, Ph.D., of McGill's physics department and their collaborator, Rob Sladek, Ph.D., of the Génome Québec Innovation Centre.

According to the team, it allows researchers to load long strands of DNA into a tunable nanoscale imaging chamber from above in ways that maintain their structural identity and under conditions that are similar to those found in the human body.

"To overcome the challenges faced by classical nanofluidic technology, we have developed a new approach for introducing tunable nanoscale confinement to trap and align DNA molecules for optical analysis," wrote the investigators. "Our confinement-based imaging technology combines nanotemplated substrates with a single-molecule imaging technique called convex lens-induced confinement (CLIC)."

CLIC will permit researchers to rapidly map large genomes while at the same time clearly identifying specific gene sequences from single cells with single-molecule resolution, a process that is critical to diagnosing diseases like cancer, explained Dr. Leslie. The CLIC tool can sit on top of a standard inverted fluorescence microscope used in a university lab. Existing tools used for genomic analysis rely on side-loading DNA under pressure into nanochannels in the imaging chamber, a practice that breaks the DNA molecules into small pieces, making it a challenge to reconstruct the genome, continued Dr. Leslie.

"It's like squeezing many soft spaghetti noodles into long narrow tubes without breaking them," she said while describing what it is like to use CLIC. "Once these long strands of DNA are gently squeezed down into nanochannels from a nanoscale bath above, they become effectively rigid which means that we can map positions along uniformly stretched strands of DNA, while holding them still. This means diagnostics can be performed quickly, one cell at a time, which is critical for diagnosing many prenatal conditions and the onset of cancer."

"Current practices of genomic analysis typically require tens of thousands of cells worth of genomic material to obtain the information we need, but this new approach works with single cells," added Dr. Sladek. "CLIC will allow researchers to avoid having to spend time stitching together maps of entire genomes as we do under current techniques, and promises to make genomic analysis a much simpler and more efficient process."

Alex Philippidis

Friday, August 01, 2014

Source: ©.shock—Fotolia.com

The FDA said Thursday it intends to regulate laboratory-developed tests (LDTs) that it deems as “high-risk” along the lines of Class III medical devices, positioning itself against academic medical centers and other developers of the tests, which have opposed efforts at imposing new rules.

The agency formally told Congress it will issue within “at least” 60 days a formal draft guidance laying out a detailed, risk-based framework for approving such LDTs [See "FDA’s LDT 'Anticipated Details'" below]. FDA sought to soften the blow for LDT developers by urging them to offer feedback on the draft guidance, and saying it would phase in regulations over several years.

While FDA has long reviewed diagnostic tests, the agency has historically exercised only enforcement discretion over LDTs designed and used within a single laboratory, and had not sought to regulate their entry to market as is now required for Class III medical devices.

LDT developers hold to the agency’s traditional view that the tests are “laboratory testing services” and not medical devices subject to the Food, Drug, and Cosmetic Act (FDCA). At present, labs certified under the Clinical Laboratory Improvement Amendments (CLIA) waiver program may develop and use their own diagnostic tests internally, without FDA oversight.

Answering a GEN question during a briefing for reporters, Jeffrey Shuren, M.D., J.D., director of the FDA’s Center for Devices and Radiological Health (CDRH), said the planned LDT guidance is an effort to reconcile the interests of nonprofit academic medical labs with those of for-profit diagnostic developers.

“Our intent here is to put in place the right balance,” Dr. Shuren said, noting that academic labs can continue using an LDT without obtaining a premarketing approval (PMA) unless another entity has won FDA approval for that test.

“That’s our attempt to try to balance continuing those incentives—for example, the academic labs saying they want to be able to meet the needs of their patients when something [an approved test] is not there—but at the same time, also have the incentives for the conventional medical device diagnostic industry to also develop tests and facilitate innovation in both spaces,” Dr. Shuren said. “That also includes the development of companion diagnostics, which are absolutely critical if we’re going to advance personalized medicine in the U.S.”

FDA also issued a final guidance addressing development, review and approval or clearance of companion diagnostics (CDx). The final guidance—issued three years after FDA’s draft CDx guidance—encourages companies to identify the need for CDx during the earliest stages of drug development, and plan for simultaneous development of a drug and its companion test.

Dr. Shuren said FDA and the Centers for Medicare and Medicaid Services, which oversees CLIA, have long viewed LDTs as medical devices since the tests have entailed chemical reads, instruments and systems used to diagnose, cure, mitigate, treat, or prevent disease. “Labs have actually sent us submissions on their tests. We don’t regulate services, and even those labs acknowledge it, because they send us traditional kinds of tests for our review, asking us for our approval.”

During the briefing, FDA Commissioner Margaret A. Hamburg, M.D., cited “faulty or unproven” LDTs leading to over- or undertreatment for disorders that included heart disease, cancer, and autism. In April, the CDC expressed “serious concerns” about the potential for misdiagnosis due to false positive results from a Lyme disease LDT that used a culture method to identify Borrelia burgdorferi. CDC recommended that the diagnosis of Lyme should be left to FDA-approved tests.

“Just as drugs need to be safe and effective for treating diseases, medical devices used to help diagnose disease and direct therapy also need to be safe and effective,” Dr. Hamburg said. “Without premarket review by the agency, neither patients, nor their healthcare providers, or the FDA itself can be assured that these tests are accurate and reliable.”

FDA acted two weeks after lab directors from 23 academic medical centers urged the U.S. Office of Management and Budget not to release an earlier draft guidance submitted to OMB. “FDA regulation of laboratory developed tests would stifle the medical innovation occurring in academic medical centers today, and interfere with our ability to care for patients,” the lab directors wrote to Brian Deese, OMB’s acting director, on July 16.

Edward R. Ashwood, M.D., president and CEO of ARUP Laboratories and professor of pathology at the University of Utah School of Medicine, led the group in arguing that new regulations would add to the cost and time spent developing new tests while stifling innovative new tests that could deliver on the long-ballyhooed promise of personalized medicine.

However, NIH Director Francis S. Collins, M.D., Ph.D., said FDA’s planned LDT guidance would advance individualized treatment: “This is good news for all who are working to turn the dream of personalized medicine into a reality.”

The lab directors sent their letter two weeks after Sen. Edward J. Markey (D-CA) and four other Democratic senators urged OMB to release the earlier draft guidance. Joining Sen. Markey were Sens. Richard Blumenthal (D-CT), Sherrod Brown (D-OH), Dick Durbin (D-IL), and Elizabeth Warren (D-MA).

FDA’s LDT "Anticipated Details"
In a letter to the Senate Committee on Health, Education, Labor and Pensions and the House Committee on Energy and Commerce, FDA said it plans to begin premarketing approval (PMA) review requirements within 12 months after a final guidance for the highest risk devices and phase it in over four years for the remaining high-risk devices. The devices would stay on the market during FDA review.

The agency said its focus on “high-risk” devices will begin with LDTs with the same intended use as a cleared or approved companion diagnostic, followed by LDTs with the same intended use as an FDA-approved Class III medical device; and some LDTs designed to determine the safety or efficacy of blood or blood products.

FDA said it “intends to” publish priority lists for its review of high-risk LDTs within 24 months of a final guidance, and “moderate-risk” LDTs within four years.

Labs would have to begin registration, listing and adverse-event reporting for “moderate risk” LDTs, which would be deemed Class II medical devices, six months after a final guidance is set. PMA for these LDTs would begin five years after final guidance, and be phased in over four years.

Friday, July 25, 2014

Source: © ktsdesign

Qiagen has acquired an exclusive global license from the University of Tokyo for the biomarker SF3B1. The company said it sees potential for developing companion diagnostics to guide myelodysplastic syndromes (MDS) treatment with new anticancer compounds under development that target the SF3B1 gene.

Mutations of this gene, which Qiagen said is a significant component of the spliceosome machinery, indicate a more favorable disease progression for patients than the wild-type gene, so testing for these gene variants could potentially provide important guidance for treatment.

Qiagen licensed the SF3B1 biomarker in an ongoing expansion of its oncohematology offering for clinical research and diagnostics. Three additional spliceosome biomarkers implicated in various blood cancers and targeting variants in the U2AF35 (U2AF1), ZRSR2, and SFRS2 genes are also part of the license agreement. They are included in Qiagen’s GeneRead DNAseq Leukemia V2 gene panel for next-generation sequencing (NGS), which has been launched earlier this month together with 13 other new cancer gene panels that are compatible with any NGS sequencer and customizable to include other genes or gene regions of clinical or biological interest.

“Building on a broad portfolio of molecular diagnostics for blood cancers, Qiagen continues to partner with clinical researchers at pharmaceutical companies and academic centers, to extend the benefits of personalized healthcare,” said Vincent Fert, Qiagen’s personalized healthcare program leader. “Because several Pharma companies are developing potential anti-cancer drugs targeting the SF3B1 gene, this biomarker also holds potential for codevelopment as a companion diagnostic.”

In May, the company partnered with Eli Lilly to codevelop universal and modular assay panels that can simultaneously analyze DNA and RNA biomarkers targeting multiple cellular pathways involved in common types of cancer and associated with several therapies Lilly is currently developing.

Thursday, July 24, 2014

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Cypher Genomics and Illumina have made a pact to co-promote Illumina's sequencing technology, the NextBio platform for data analytics and storage, and Cypher's Coral™ biomarker discovery service to pharmaceutical companies. The firms, through Illumina's sales team, will be promoting the products and service together as part of a solution that, they say, can facilitate development of genomic-based biomarkers from whole-genome sequence data for clinical trials and precision medicine.

Cypher says its technology can reduce the signal-to-noise in genomic information to help researchers find important biomarkers in sample sizes of the sort frequently used in early-stage drug development. It also claims that its genomic analysis platform can provide highly accurate genome annotations to enable biomarker discovery studies with sample sizes in the hundreds, which the firm believes would aid many researchers working on Phase II trials.

Nick Naclerio, svp, corporate development and general manager, Enterprise Informatics of Illumina, said in a statement that Coral complements Illumina's whole-genome sequencing and NextBio platform nicely. "We look forward to working with Cypher Genomics to provide our mutual customers with the sequencing, data interpretation, and data mining they require for biomarker discovery with whole-genome data," he added.

Illumina has had a very good year so far: Just yesterday, the firm announced record second-quarter financial results, including a revenue of $448 million, an increase of 29% compared to $346 million in 2013's second quarter. Commenting on the results, Illumina's CEO Jay Flatley said, "With the most extensive sequencing portfolio available, we remain extremely well-positioned to develop and address the large and untapped market opportunities ahead of us."

Alex Philippidis

Wednesday, July 23, 2014

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Fulfilling the promise of personalized medicine will require more patient education, greater access to treatments, and new commitments by insurers to pay for the new drugs, an umbrella group that represents more than 200 academic, industry, patient, provider, and payer communities said today.

The Personalized Medicine Coalition (PMC) cited a survey it commissioned that showed only 38% of respondents had ever heard of “personalized medicine”—the targeting of new drugs to patients most likely to benefit from them, using diagnostics to identify biomarkers.

PMC and other proponents say personalized medicine has the potential to revolutionize disease treatment and contain spiraling healthcare costs. Only 11% of those surveyed said their doctor had discussed or recommended personalized medicine to them.

Amy M. Miller, Ph.D., evp of PMC, told GEN the coalition thinks one reason for the lack of patient awareness was the dearth of personalized medicine products and services until lately. That number has climbed, according to PMC, from 13 a decade ago to 113.

“Personalized medicine leads the way in cancer, but there are fewer examples in chronic disease conditions, and I think that’s the other reason why awareness is low,” Dr. Miller said.

A key role in raising patient awareness of personalized medicine, she added, will be played by providers: “They have a very large role to play in raising awareness with the general population about what personalized medicine is and how it can impact healthcare and improve quality.”

During a panel discussion of survey results at the National Press Club in Washington, D.C., Dr. Miller joined three experts in agreeing that advancing personalized medicine will require professionals to agree on a term of art—all agreed on personalized medicine—and to publicize successful treatments.

“If an expectant mother would be able to say that a genetic test might be able to identify if her fetus is going to be healthy, that’s important,” said Raju Kucherlapati, Ph.D., Paul C. Cabot Professor in the Harvard Medical School Department of Genetics. “For a patient who is suffering from cancer to be able to hear us say, ‘What is the drug or combination of therapies that is most likely to be effective in your case?’ That’s what resonates with people.”

Dr. Kucherlapati was joined on the panel by Randy Burkholder, vp of policy at Pharmaceutical Research and Manufacturers of America (PhRMA); Donna Cryer, J.D., president and CEO of the Global Liver Institute; and Mark Richards, svp and management supervisor with survey conductor KRC Research. They joined Dr. Miller in unveiling findings from the survey, which questioned 1,024 American adults by landline and mobile phone from March 5–16. The margin of error for the total sample was plus or minus 3 percentage points.

According to the survey, almost two-thirds of respondents (65%) reacted mostly positively to a description of personalized medicine, with 37% saying they were very likely to undergo a diagnostic test toward an individualized treatment plan. Another 40% said they were “somewhat’ likely.

However, more than two-thirds of patients pinpointed two overlapping concerns with personalized medicine—that their insurers won’t cover it (69%) or they cannot afford it (67%).

PMC is calling for insurers to fund new personalized treatments. That is near-certain to be resisted by the payers, which have balked at reimbursing providers for the sky-high price of new drugs designed for subpopulations and want drug developers to shoulder more of the cost. Drugmakers also balk at paying more, contending that it would slow down the development of new medicines, and that they need to recoup R&D expenses.

Yet the developers face growing political pressure to contain drug costs. Since March, four Democrats in the Republican-majority U.S. House of Representatives have criticized Gilead Sciences for charging $84,000 per 12-week treatment for the chronic Hepatitis C virus treatment Sovaldi™ (sofosbuvir). One of the four, U.S. Rep. Henry A. Waxman (D-CA) is set to join two advocacy groups Wednesday in calling for reduced Medicare drug costs.

Waxman is ranking member of the House Committee on Energy and Commerce, which on Wednesday will host a “21st Century Cures” roundtable talk on personalized medicine whose speakers will include PMC President Edward Abrahams, Ph.D.

“We need to have a conversation about how to streamline development and approvals for personalized medicine products and services”—both drugs and diagnostics, Dr. Miller said. “We need to talk about how to streamline FDA processes for co-developed drug-diagnostic combination products, how to get those to market more quickly. And when we talk about a standalone diagnostic, we need to talk about what kind of evidence needs to be presented to payers, so they feel comfortable and confident in covering those innovative tests.”

She said payers can be persuaded to support new tests that show clear benefits, citing recent decisions by insurers to reimburse providers for noninvasive prenatal tests for trisomy disorders such as Down syndrome.

“We see this as an opportunity to discuss what personalized medicine means holistically,” Dr. Miller said. 

Monday, July 21, 2014

Source: © Elena Kovaleva - Fotolia.com

Berry Genomics chose Illumina's next-generation sequencing technology as the platform on which Berry will aim to secure Chinese Food and Drug Administration (CFDA) regulatory approval for clinical applications. The goal is to expand access to NGS-based tests in China.

The companies say have co-developed an NGS system to provide a cost-effective, easy-to-use assay for noninvasive prenatal testing. A working version of the new assay and instrument system has been validated in clinical settings in China, and is in late-stage review under the CFDA's medical device registration process.

The new system integrates Berry Genomics' Bambni™ assay, which includes a library preparation kit, analysis software, and a sequencing instrument based on Illumina's NextSeq™ 500 sequencing system.

"There are two million high-risk and advanced maternal age pregnancies a year in China, which is about three times the size of the U.S. market. We need to ensure we are addressing women's needs by offering a safe and proven technology. As the first and only company with a U.S. FDA cleared next-generation sequencing instrument, Illumina is an ideal collaboration partner given their experience," said Daixing Zhou, CEO of Berry Genomics.

"This agreement is an example of our commitment to working with clinical companies in China and worldwide who want to develop and commercialize in vitro diagnostics based on next-generation sequencing," added Greg Heath, svp, IVD development at Illumina.

Thursday, July 17, 2014

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Beckman Coulter said today it agreed to acquire the clinical microbiology business of Siemens Healthcare Diagnostics for an undisclosed price.

Siemens’ clinical microbiology business specializes in microbial identification and antibiotic sensitivity testing (ID/AST). The business operates with an installed base of over 6,000 instruments globally, and is part of Siemens’ diagnostics division, which finished last year with $5.332 billion (€3.942 billion) in revenue.

Today’s announcement by Beckman Coulter—an indirect, wholly owned subsidiary of Danaher—ends months of speculation over the future of Siemens’ clinical microbiology business. In March, BioMerieux CEO Jean-Luc Belingard told Reuters his company would look at acquiring the business from Siemens, which the wire service said had been offering through bankers “around $500 million” for its clinical microbiology operations, citing unnamed sources.

Siemens’ microbiology product line includes the MicroScan® Instruments and MicroScan panels/consumables, along with data management solutions. The MicroScan systems are designed to deliver high accuracy and superior detection of emerging resistance.

“The clinical microbiology business will be an excellent complement to Beckman Coulter's Diagnostics business with a strong reputation and market position,” Beckman Coulter Diagnostics President Arnd Kaldowski said in a statement. “Adding its ID/AST solutions to our existing products and services will create an opportunity to enhance our offerings to laboratory customers and improve patient care.”

Kaldowski added that the acquisition will expand Beckman Coulter’s product portfolio with differentiated analytical systems that elevate the company’s clinical capabilities for customers, while driving continued growth.

Siemens’ deal with Beckman Coulter is expected to close in the first quarter of 2015, subject to regulatory approvals and other customary closing conditions.

Earlier this month, Bloomberg reported that Siemens was looking to refocus on its energy and industrial businesses, citing unnamed sources as saying the German conglomerate was also looking to sell off its hospital database and IT business.

Adding credence to that talk was Siemens restructuring its operations in May, in part by giving greater operational independence to its healthcare businesses. CEO Joe Kaeser at the time insisted that the action was not intended to signal a sell-off but to increase their ability to address a changing market.

However, Morningstar analyst Debbie Wang speculated to the Boston Business Journal that Siemens may still wish to grow in diagnostics, saying the company was one of two most likely suitors for Alere. The comment followed a shakeup of Alere’s management that led an outspoken shareholder to say publicly that the point-of-care diagnostics developer had received unsolicited offers from potential strategic acquirers in the past year. 

Alex Philippidis

Thursday, July 17, 2014

To increase the chances of being successful, MDx labs should decide on a suitable menu of molecular tests that align with available resources early on. [©.shock—Fotolia.com]

Bringing molecular testing to the clinic is now easier than in past years, thanks to deeper knowledge about the genome and gene variants, increased automation and efficiency, user-friendlier technology, and improved methods to monitor quality.

Incorporating these and other basics into a successful molecular diagnostics (MDx) lab requires clinicians to address opportunities and challenges much as in creating any other lab. In many cases, that means managers must develop business plans that show administrators how their MDx lab intends to succeed clinically and financially. There’s a lot of competition: More than 600 medical laboratories nationwide, plus another 200 independent labs, carry out molecular diagnostics tests.

For the rest of the story, click here.

Alex Philippidis

Thursday, July 17, 2014

Greg Lucier has made his first investment since his days as chairman and CEO of Life Technologies as a member of the investor group behind Edico Genome.

A San Diego startup whose technology promises to enable the clinical use of genomics by radically reducing the cost and time of analyzing next-generation sequencing (NGS) data is attractive enough to have drawn Gregory Lucier among investors that have joined to raise $10 million in Series A financing.

Lucier has made his first investment since his days as chairman and CEO of Life Technologies as a member of the investor group behind Edico Genome, which announced the financing today and said it plans to bring to market its Dynamic Read Analysis for Genomics (DRAGEN) Bio-IT Processor this fall.

The group was led by Qualcomm’s venture investment group Qualcomm Ventures, and included Axon Ventures—as well as Lucier, who will join Edico’s board of directors: “Edico Genome's solution to speed data analysis and lower costs has the potential to have a large impact on many areas of medicine, particularly in oncology and noninvasive personal testing,” Lucier said in a statement.

According to Edico, DRAGEN slashes the time needed to analyze a whole human genome from 24 hours to just 18 minutes, while retaining the accuracy of today’s analysis carried out by clusters of large servers. A single DRAGEN accelerator card can do the work of the 50 servers needed to analyze, for example, the more than 18,000 whole human genomes a year produced by a full Illumina HiSeq X Ten system, at a savings of $6 million over four years. That savings includes reduced compute requirements, lower overhead costs (such as for IT staff, power, and rack space), and reduced data upload costs and data storage costs, since DRAGEN also compresses the raw data for long-term storage.

Introduced in January at the JP Morgan Healthcare Conference, HiSeq X Ten dazzled investors and others by breaking the $1,000-genome sequencing cost barrier—a figure that includes reagents and sample prep, DNA extraction, hardware, and labor. DRAGEN is designed to lower that expense further by drastically cutting hardware costs, which Illumina has estimated at $137, assuming 116 “runs” per year per system, each run sequencing 16 genomes, and four-year depreciation.

“If you look at HiSeq X Ten and you do [analysis] on servers, including storage and everything, all that processing, etc., it’s about $150 per whole-genome sequence. Ours is a fraction of the cost—maybe in the $20–$30 kind of range,” Edico’s CEO, Pieter van Rooyen, Ph.D., told GEN.

Dr. van Rooyen likens Edico’s technology to the smartphones that have supplanted the brick-sized cellphones of a generation ago, which in turn he likens to today’s NGS analysis tools: “They’re where cellphones were in the ‘80s, big and clunky. What we’re doing is aiming to bring sequencing, in terms of the processing of data, out of the ‘80s, at least into the ‘90s, but we have the fundamental technology to bring it all the way into the iPhone of the future, if you will.”

The technology, according to Edico, is the world’s first NGS bioinformatics application-specific integrated circuit (ASIC). Embedded on a PCIe form factor card, DRAGEN will be sold with accompanying software as a platform-as-a-service or Paas platform for integration into sequencers and NGS bioinformatics servers. DRAGEN uses a processor with algorithms for mapping, alignment, sorting, and variant calling.

Instead of analyzing the torrent of sequencing data in software through a general purpose processor, Dr. van Rooyen said, DRAGEN uses its own dedicated processor that runs the tailored algorithms: “We have architecture on our chip that facilitates the movement of the data and the processing of the data in an optimal way. That’s why we can do it on one chip as opposed to an all-server form of Intel CPUs.”

Dr. van Rooyen is one of three founders of Edico. The others are Robert McMillen, Ph.D., vp of engineering, and Michael Reuhle, director of system architecture. DRAGEN will be launched commercially during the American Society of Human Genetics’ 64th Annual Meeting, set for October 18–22 in San Diego.

“We believe genomics is the future of healthcare, and our technology is really enabling the uptake of genomics,” Dr. van Rooyen said. “Hopefully in five or 10 years, everybody’s going to have a personalized sequencer, and our technology is just a first step on the processing side in realizing that kind of future. It’s a fundamental technology that can be extended to the future and allow the processing of the data in a very simple, dedicated chip.”

He said a huge part of Edico’s success to date has been its ability to benefit from EvoNexus™, the business incubator of CommNexus™, a nonprofit high-tech trade organization in San Diego. Edico is one of 28 startups housed by EvoNexus, through which Edico connected with its investors, including Qualcomm as well as Lucier, whose Life Tech was acquired by Thermo Fisher Scientific for about $13.6 billion, plus assumption of $1.5 billion in net debt, in a deal completed February 3.

The incubator has a relationship with Qualcomm through the Qualcomm Labs initiative, which facilitated an earlier seed investment in Edico by Qualcomm Ventures—and led to the financing from Qualcomm Ventures.

Richard Mazzarella, Ph.D.

Wednesday, July 16, 2014

The first printout of the human genome as displayed at the Wellcome collection, London [Russ London—Wikicommons]

The Human Genome Project provided a path for determining the genetic basis of many inherited diseases and neoplasms. So far, various efforts from both research institutions and private companies have yielded myriad single gene and disease panel tests for both cancer and various Mendelian diseases, which have proven quite useful in diagnosing and treating specific conditions. The scope of single gene tests is limited, making them less effective at identifying a patient’s underlying disease state and appropriate cancer drug regimens. Large cancer panels containing all the actionable genes do better at elucidating this type of information. The maturation of next-generation sequencing (NGS) technology, though, has made whole-exome and whole-genome studies viable options, especially if they can be used to assemble a mineable knowledge base that could yield a more comprehensive understanding of disease.

For the rest of the story, click here.

Gary E. Marchant and Rachel A. Lindor

Wednesday, July 16, 2014

Medical malpractice lawsuits are a double-edged sword. On the one hand, liability can compensate injured patients and push providers to implement the most up-to-date technologies and practices. On the other, the threat of liability can result in wasteful defensive medicine and drive up insurance premiums.

New medical technologies such as personalized medicine trigger both edges of the liability sword. On the positive side, the threat of liability may compel providers to more quickly uptake useful genetic tests and data, but on the negative new liability risks and uncertainties created by personalized medicine may incentivize premature or inappropriate utilization of genetic tests and drive up insurance premiums.

For the rest of the story, click here.


Patricia Fitzpatrick Dimond, Ph.D.

Wednesday, July 16, 2014

Determination of an individual’s risk for severe arrhythmias before a life-threatening event occurs remains a significant medical challenge. [© kmiragaya - Fotolia.com]

Advances in molecular diagnostics, physicians say, have the potential to improve identification of cardiac diseases and further understanding of mechanisms responsible for their pathogenesis and phenotypic expression. These tests may also predict the need for specific treatment, or help avoid unnecessary therapies and invasive diagnostic procedures.

And, scientists add, while genomic research in cardiovascular disease (CVD) has progressed rapidly over the last few years, “groundbreaking observations” have not yet been accompanied by clinically applicable tools for risk prediction, diagnosis, or therapeutic interventions.

For the rest of the story, click here.

Dan Koboldt

Wednesday, July 16, 2014

Comprehensive molecular profiles of the most common cancer types are now available. [NHGRI]

As you have probably noticed, there’s been a major shift in the focus of next-gen sequencing over the past couple of years. First it was all about new genomes, new techniques, and discovery. Now it’s all about translation. We are entering a new era in next-gen sequencing, one in which NGS technologies will not only be used for discovery, but will be integrated into clinical care.

A review in the latest issue of Human Molecular Genetics discusses NGS-enabled cancer genomics from the clinician’s point of view. In it, the authors highlight recent findings from large-scale cancer genomics efforts—such as the Cancer Genome Atlas—and offer their perspectives on the significant challenge facing us: translating the knowledge from such massive “oncogenomic” datasets to the clinic.

For the rest of the story, click here.

Wednesday, July 16, 2014

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

Clinical OMICs Issue 7

Monday, July 14, 2014

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Stanford University School of Medicine researchers say they have developed an inexpensive, portable, microchip-based test for diagnosing type 1 diabetes that they believe could improve patient care worldwide and help researchers better understand the disease.

Described in a paper (“A plasmonic chip for biomarker discovery and diagnosis of type 1 diabetes”) published in Nature Medicine, the test employs nanotechnology to detect type 1 diabetes outside hospital settings. The handheld microchips distinguish between the two main forms of diabetes mellitus, which are both characterized by high blood-sugar levels but have different causes and treatments.

Until now, making the distinction has required a slow, expensive test available only in sophisticated healthcare settings, according to Brian Feldman, M.D., Ph.D., assistant professor of pediatric endocrinology, the Bechtel Endowed Faculty Scholar in Pediatric Translational Medicine, and the senior author of the paper. The scientists are seeking FDA approval of the device.

“With the new test, not only do we anticipate being able to diagnose diabetes more efficiently and more broadly, we will also understand diabetes better, both the natural history and how new therapies impact the body,” said Dr. Feldman.

Better testing is needed because recent changes in who gets each form of the disease have made it risky to categorize patients based on their age, ethnicity, or weight, as was common in the past, and also because of growing evidence that early, aggressive treatment of type 1 diabetes improves patients' long-term prognoses, continued Dr. Feldman.

Decades ago, type 1 diabetes was diagnosed almost exclusively in children, and type 2 diabetes almost always in middle-aged, overweight adults. The distinction was so sharp that lab confirmation of diabetes type was usually considered unnecessary, and was often avoided because of the old test's expense and difficulty. Now, because of the childhood obesity epidemic, about a quarter of newly diagnosed children have type 2 diabetes. And, for unclear reasons, a growing number of newly diagnosed adults have type 1.

Type 1 diabetes is an autoimmune disease caused by an inappropriate immune-system attack on healthy tissue. As a result, patients' bodies stop making insulin, a hormone that plays a key role in processing sugar. The disease begins when a person's own antibodies attack the insulin-producing cells in the pancreas. The autoantibodies are present in people with type 1 but not those with type 2, which is how tests distinguish between them.

“Delayed diagnosis of T1D [type 1 diabetes] can result in severe illness or death, and rapid diagnosis of T1D is critical for the efficacy of emerging therapies,” wrote the investigators. “However, attempts to apply next-generation platforms have been unsuccessful for detecting diabetes biomarkers. Here we describe the development of a plasmonic gold chip for near-infrared fluorescence–enhanced (NIR-FE) detection of islet cell–targeting autoantibodies. We demonstrate that this platform has high sensitivity and specificity for the diagnosis of T1D and can be used to discover previously unknown biomarkers of T1D.”

In addition to new diabetics, people who are at risk of developing type 1 diabetes, such as patients' close relatives, also may benefit from the test because it will allow doctors to quickly and cheaply track their autoantibody levels before they show symptoms, explained Dr. Feldman, who added that because the test is so inexpensive, it may also allow the first broad screening for diabetes autoantibodies in the population at large.

Monday, July 14, 2014

Source: © London_England - Fotolia.com

Transplant Genomics (TGI) now has an exclusive license to patent rights co-owned by The Scripps Research Institute and Northwestern University that could form the basis for clinical tests to improve management of organ transplant recipients. TGI is planning to use the technology to develop and commercialize tests that use genomic markers of transplant graft status as part of program to detect and respond to early signs of graft injury in patients.

This licensing agreement gives TGI access to intellectual property related to kidney and liver transplant diagnostics including immune status monitoring and optimization. TGI says its first test will be used to monitor kidney transplant recipients, indicating when treatment or biopsy is required based on analysis of a patient’s blood.

Michael Abecassis, M.D., founding director and chief clinical advisor of TGI, said in a statement that the tests could be used to watch patients with good kidney function to aid in immunosuppression decisions. "The test will also find a major and immediate application in circumstances where a sudden elevation in creatinine is noted by the clinician and a biopsy is not possible because of logistical issues," he added.

"The scientific founders of TGI have uniquely combined biomarker discovery with clinical validation and insight to set the stage for high-impact collaborations designed to move the transplant field forward," commented Stanley Rose, Ph.D., president & CEO of Transplant Genomics. Dr. Rose is himself the recipient of a kidney transplant.

Syamala Ariyanchira, Ph.D.

Thursday, July 10, 2014

A recent report estimates the global demand for PCR technologies in 2013 to be around $10.6 billion. [Caleb Foster - Fotolia.com]

The polymerase chain reaction (PCR) has come a long way during the past three decades to become one of the fundamental platforms in life sciences sector. Normally, this is a sufficiently long period for a technology to mature and the market to move to decline phase. However, the PCR industry is witnessing increasing excitement both in terms of innovation and demand. The expiry of key PCR patents is one of the major factors driving this growth allowing more companies to get involved. These new and emerging companies are actively involved in developing new applications and expanding the market to various end-use segments. Even though the technology is considered mature, the demand is still on the rise due to this market expansion. Enthusiasm in the emerging markets is particularly visible and is a major driver of the demand. Overall, these developments are offering improved accessibility to PCR-based diagnostics and other products.

Automation and multiplexing are improving the technology in terms of its ease-of-use and speed making the technology more user-friendly and effective. These critical factors have significant impact in end-use markets. For instance, physicians are adapting to PCR-based screening and disease diagnosis in critical medical diagnostics areas even in emerging countries. Responses from regulatory bodies across the regional markets are also promising, encouraging the utilization of PCR tests in various end-use segments.

Even in this almost “post-patent era” of PCR, the market players are facing significant challenges while treading in the murky waters of PCR patents. Careful analysis to identify patents that are still enforceable is needed, depending upon the markets being considered. The high cost of commercial PCR assays is another challenge, particularly in clinical diagnostics field. Alternate technologies such as NGS are also emerging as threats to the PCR market, since they have the potential to make PCR obsolete in many end-use segments as their cost efficiency improves. The emergence of dPCR could also prove to be a threat to real-time PCR in at least some of the end-use segments. Digital PCR is currently in its initial growth stages, and the application of the technology in various clinical segments is being actively promoted by the technology suppliers.

The recent report published by AcuBiz Consulting titled “The Worldwide Markets of PCR Technologies” estimates the global demand for PCR technologies in 2013 to be around $10.6 billion. The demand grew from 2012 by 6.1% in 2013. The market is expected to grow at a compound annual growth rate (CAGR) of approximately 8% to reach $15.6 billion by 2018. Regionally, the report divides the global market into North America, Europe, Asia Pacific (APAC), and ROW. While North America is expected to show continuous growth trends, growing at a CAGR of 6.1%, the APAC region shows the highest growth potentials. This region is forecasted to grow at a CAGR of 11.2%.

In terms of end-use segments, the largest application segment for PCR products in 2013 was medical diagnostics, as presented in Figure 1. The demand for PCR products for medical diagnostics applications is expected to grow at a CAGR of 8% between 2013 and 2018. The largest subsegment within medical diagnostics is infectious disease diagnostics. There is a rising demand from patients as well as physicians for speedy and accurate diagnosis at affordable costs, which is driving the demand for PCR assays in the medical diagnostics field, even in emerging markets.

Figure 1. Global demand for PCR technologies by end-use segments, by value (USD, billions).

Figure 1. Global demand for PCR technologies by end-use segments, by value (USD, billions).

Detailed patent analysis with respect to various PCR technologies during the past three decades shows growing patenting trends in all the key end-use segments. The patent analysis clearly indicates a rise in PCR application development activities in these segments, as expected after the expiry of key PCR patents. Cancer, infectious diseases, and food safety testing include some of the other major end-use segments where activities related to patenting of PCR diagnostics tools are highly intense. Cancer has been an area of focus of PCR patents since its early years. The intensity of patenting in this area is still high and growing strong as indicated in Table 1, where the number of patents related to key oncology segments during the past decade and the past three years are compared. For instance, leukemia-related PCR patents accounted for almost 25% of the total PCR patents indicating that PCR is a cornerstone of molecular diagnosis in leukemia research.

Table 1. PCR-based diagnostics—patenting trends in selected cancer segments. <sup>a</sup>

Table 1. PCR-based diagnostics—patenting trends in selected cancer segments. a

In general, many different types of cancers became the focus of PCR assay developers during the past decade, and the trend is intensifying as evident from the increasing numbers of patents during the past three years in Table 1. Occasionally, the increasing patenting activities are in correlation with the launch of novel drugs or vaccines indicating a sudden rise of focus on the targeted disease by the healthcare industry. For example, the launch of the Gardasil vaccine in 2006 against HPV and hence as potential prevention for cervical cancer could have influenced the rise in patenting activities related to cervical cancer diagnostics during the past decade, which is still continuing as indicated by the number of hits during the past three years. 

Regulatory landscapes play significant roles in influencing the growth of PCR markets. The emergence of PCR as an important tool in various end-use segments across the globe is in accordance with the increasing approval by regulatory authorities in the regional markets. Key regional markets are analyzed in detail in the report for understanding the regulatory landscapes. The medical diagnostics and food safety testing segments where application of PCR tools are becoming popular, leading to increased attention from regulatory agencies, are particularly analyzed since more regulations can be expected in these fields during the forecast period. The report includes analyses of various guidelines regarding PCR data collection and interpretation in key end-user market segments.  

The PCR market is consolidating as key players are being bought over by bigger diagnostic companies. The acquisition of Life Technologies by Thermo Fisher Scientific in February 2014 is a typical example of this market trend. However, the numbers of new market entrants are increasing. The focus of many of these new companies includes development of new PCR diagnostic products targeting new end-use segments. Some of these companies are based in emerging markets such as India, China, Korea, Southeast Asia, Latin America, and Eastern Europe. While most of these are small and startups, their influence in shaping the demand in their respective domestic markets cannot be ignored.  

Syamala Ariyanchira, Ph.D., (syamala@acubiz.com.co) is a principal consultant at AcuBiz Consulting, a Malaysia-based life sciences consulting firm.

Thursday, July 10, 2014

Source: Andrzej - Fotolia.com

Genetic counseling services provider InformedDNA released today a white paper on genetic testing. Use of these diagnostic tests is growing rapidly, but inappropriate testing has negative consequences for individuals and the U.S. health care system, according to the company.

The paper, titled Genetic Counseling: Connecting Patients to the Power of Genetics and authored by Rebecca Sutphen, M.D., Amber Trivedi, and Kelle Steenblock, delves into the complexity of testing, gaps in physician understanding, issues regarding access, current guidelines, and the role of trained genetics specialists in helping patients maximize the effectiveness of genetic testing, while avoiding unnecessary, wasteful testing.

"Genetic counseling provided by trained specialists can bridge the gap between patients and the appropriate use of genetic testing. It provides an evidence-based solution that allows specialists to ensure the right patient gets the right test," said Dr. Sutphen, president and chief medical officer of InformedDNA. "The results of a genetic test can also have an enormous impact on future health care-related choices. Genetics specialists help patients evaluate their results and make more informed choices based on the best and most current information available."

While genetic testing can provide a life-saving service, it only paints a partial picture of a patient's health risks. To accurately determine a patient's risk-profile, the following steps are taken by genetic specialists:

  • Conduct a complete personal and family history risk assessment.
  • Determine whether a patient is appropriate for genetic testing and, if so, which test is right for them.
  • If a test is ordered, interpret the results in the context of the patient's family history and help them develop a personalized care plan in coordination with their physicians.

However, there are gaps in physician knowledge of genetics and with more than 10,000 genetic tests available, it's not surprising that as many as half of tests are ordered inappropriately. Misuse of genetic testing can carry a number of unintended consequences. In 2010, annual spending on genetic testing eclipsed $5 billion and could reach $25 billion within a decade.

As payers continue to look for ways to reduce costs, consulting with genetic specialists can safeguard insurers against paying for diagnostics that are not medically useful, while also improving quality of care.

"Inappropriate testing can have unintended consequences for patients, even beyond their individual health," noted Steenblock, InformedDNA's senior vp for clinical services. "Genetic counselors help patients navigate these difficult issues."

Wednesday, July 09, 2014

Source: © Alex Tihonov - Fotolia.com

Scientists at the Icahn School of Medicine at Mount Sinai, along with colleagues in the U.K. and Spain, report they discovered that key genetic variants may affect how cancer patients respond to radiation treatments. The research team found that variations in the TANC1 gene are associated with a greater risk for radiation-driven side effects in prostate cancer patients, which include incontinence, impotence, and diarrhea.

The current results are based on a genome-wide association study (“A three-stage genome-wide association study identifies a susceptibility locus for late radiotherapy toxicity at 2q24.1”) published in Nature Genetics.

“Our findings, which were replicated in two additional patient groups, represent a significant step toward developing personalized treatment plans for prostate cancer patients,” said Barry S. Rosenstein, Ph.D., professor, radiation oncology, genetics and genomic sciences, Icahn School of Medicine at Mount Sinai. “Within five years, through the use of a predictive genomic test that will be created using the data obtained in the recent study, it may be possible to optimize treatment for a large number of cancer patients.”

For the study, Dr. Rosenstein and his team obtained blood samples from nearly 400 patients who were receiving radiotherapy treatment for prostate cancer. The blood samples were screened for roughly one million genetic markers, and each patient was monitored for at least two years to track incidents of side effects from the radiation. Data analysis showed which genetic markers were consistently associated with the development of complications following radiotherapy.

“[Our] results, together with the role of TANC1 in regenerating damaged muscle, suggest that the TANC1 locus influences the development of late radiation-induced damage,” wrote the investigators.

“The next step is to validate the results, and see if the same markers predict similar outcomes in patients with other forms of cancer,” explained Dr. Rosenstein. Using the genomic test being developed, treatment plans can be adjusted to minimize adverse effects thereby allowing for an improved quality life for many cancer survivors.

Monday, July 07, 2014

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Sequence-based clinical diagnostics firm and deCODE genetics spinout NextCODE Health is partnering with the Academic Centre on Rare Diseases (ACoRD) at University College Dublin, allowing ACoRD to use NextCODE products in research aimed at learning more about the causes and better ways to diagnose autism and rare diseases.

NextCODE's Clinical Sequence Analyzer™, which the firm says can identify causal mutations in families with different rare disorders, and Sequence Miner and the GOR™ database infrastructure, to be used for mining whole-genome data for sequence variants linked to autism spectrum disorders, are among the technologies to be used.

Sean Ennis, Ph.D., director at ACoRD, UCD School of Medicine and Medical Science, and co-founder of the Irish Autism Genetics Collaboration said in a statement that ACoRD wants to establish a reputation for being a center of excellence in the field of rare genomics. "Sequencing is a powerful means to identify the causes of disease, but it requires the ability to efficiently store and query truly vast amounts of data. NextCODE's system has done this on an unparalleled scale, and can deliver diagnoses on a case-by case basis and enable large-scale discovery efforts," he added.

NextCODE Health was launched with $15 million in venture capital back in October after securing a five-year exclusive license for sequence-based clinical diagnostic applications using technology developed by deCODE genetics. NextCODE says the deCODE system has enabled over 350 publications in gene discovery, diagnostics, and medical applications.

Monday, June 30, 2014

Illumina's HiSeq 2500

Illumina entered three separate deals with three European labs under which they will use Illumina's consumables and the HiSeq 2500 to develop and perform noninvasive prenatal testing (NIPT) in their respective nations. French lab-testing service firm Biomnis will make NIPT available in France, Italian molecular genetics lab Genoma will perform NIPT services in Italy, and the Center for Human Genetics and Laboratory Diagnostics Martinsried (near Munich) will offer NIPT in Germany.

Earlier this year at the JP Morgan 32nd Annual Healthcare Conference, Illumina said it planned to expand its offerings based on the verifi® laboratory-developed NIPT, which the firm picked up upon acquiring noninvasive prenatal testing firm Verinata Health last year. Tristan Orpin, Illumina's svp and general manager of reproductive and genetic health, said in a statement that he feels these three agreements will help establish the firm as a global leader in reproductive and genetic health solutions and a partner for next-generation sequencing-based testing for clinical applications.

Francesco Fiorentino, Ph.D., CEO and director of Genoma Group Laboratories, said that the Italian lab chose to work with Illumina because of its deep sequencing capabilities. "We are continuously trying to improve our service and offerings for patients and healthcare providers, and we believe our physician customers and the expectant families they work with will be thrilled to have access to this important information in an accurate, safe, and efficient manner," he added.

"Backed by whole-genome sequencing, we look forward to making our highly accurate test accessible to physicians and their patients," commented Charles Woler, M.D., Ph.D., CEO of Biomnis Laboratories.

John Sterling

Thursday, June 26, 2014

Source: © kentoh - Fotolia.com

Consider this scenario:

“In five or ten years, you will show up at your doctor’s office, not feeling well, with a thumb drive that contains all your important health-related information, including a copy of your entire genome. Your physician will run the disk through a sophisticated computer and, after studying the results, prescribe a treatment, maybe even a form of genetic engineering or gene therapy, based on the genomic components of your disease, not just your symptoms.”

Fact or Fiction?

“The full-blown version of this five-year scenario is fiction,” says David Smith, Ph.D., professor of laboratory medicine and pathology at the Mayo Clinic. “Now having your genome on a disk in five years will very likely be a reality but being able to fully interpret your genome’s data and make a clinically important decision remains more in the realm of fiction.”

For the rest of the story, click here.

Mitzi Perdue

Thursday, June 26, 2014

Sharon Terry is president and CEO of Genetic Alliance.

The task of finding and recruiting sufficiently large cohorts for studying genetic diseases has up to now been a needle in the haystack problem. This is rapidly changing as Sharon F. Terry, and her colleagues at Genetic Alliance are making possible aggregation of individual health information in ways and on a scale never seen before. In the process, they may play an unprecedented role in speeding up drug discovery while enabling individuals to have more ownership of and participation in their own health.

Terry heads Genetic Alliance, an organization composed not only of more than 1,200 disease-specific health advocacy organizations, but another 8,000 or so university, government, and private sector groups. Having such a large number of organizations working together may soon make possible research that up until now would have been impossible.

For the rest of the story, click here

Alex Philippidis

Thursday, June 26, 2014

Incidental findings occur in clinical, research, and direct-to-consumer contexts. [Photocanal25/iStock Photos]

Recent developments reveal both the beginnings of consensus, and many more unresolved issues, when it comes to “incidental” or unexpected findings uncovered during genome or exome sequencing.

The American College of Medical Genetics and Genomics (ACMG) retreated in April from its controversial recommendation last year that labs should return incidental findings to the doctor ordering the sequencing for discussion with patients regardless of their preference. The suggestion applies to ACMG’s minimum list of 57 genes it recommends be sequenced for mutations involving any of 24 disorders “where early intervention is likely to reduce or prevent serious morbidity or early mortality.”

ACMG argued last year that genes should be sequenced no matter a patient’s age or indication that triggered the sequencing, while patients who refused consent should not be sequenced. After criticism from numerous physicians, other clinicians, and patient advocates, ACMG now recommends that patients should have the choice of opting out of analysis of their medically actionable genes following whole exome or genome sequencing.

For the rest of the story, click here.

Chris Anderson

Thursday, June 26, 2014

Celgene is using NanoString’s nCounter analysis system to support the clinical validation and development of a companion diagnostic for Revlimid, for treatment of Diffuse Large B-Cell Lymphoma.

As recently as ten years ago, just after completion of the Human Genome Project, the concept of a personalized approach to cancer treatment was largely just that—an idea of what could be. And companion diagnostics were limited to predicting patient response to Herceptin for breast cancer and Gleevec for chronic myelogenous leukemia.

But it was the introduction of these therapies along with the nascent field of gene sequencing that began to move the treatment of cancer from a broad-based, one-size-fits-all approach to one that seeks to better understand the unique underlying molecular pathology of each patient’s cancer.

“In the 1990s the pharmaceutical companies argued that because the cancer population is small the only way you could develop a drug and profit from that was by using a broad spectrum chemo approach,” said Richard Ding, CEO of bioTheranostics, a provider of prognostic and diagnostic cancer tests. “Because then you can hit on multiple tumor types and have a broad cluster.

“I think the poster child for changing this was Herceptin. It was able to demonstrate that even though the target population for breast cancer of 50,000 or 60,000 was once considered too narrow, that even with the complexity of making monoclonal antibodies, it showed you can make a business out this.”

For the rest of the story click here.

Thursday, June 26, 2014

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

Clinical OMICs Issue 6

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.”

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. 

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.

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.”

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.

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.

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.

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.

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.

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

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.”

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.

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.

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.

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.


  • 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.

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.

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.”

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.

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.

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.

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.

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

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.

Kevin Mayer

Wednesday, May 21, 2014

Source: © Juan Gärtner - Fotolia.com

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.”

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."

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.


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

Click here to register

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.

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.

Friday, May 16, 2014

Source: © uwimages - Fotolia.com

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.

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

Shawn C. Baker

Thursday, May 15, 2014

Source: © Mopic - Fotolia.com

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.

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.

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.


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.

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.”

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.”

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.

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

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.”

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

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.”

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.

Kevin Mayer

Thursday, April 17, 2014

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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.”

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.

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.

Friday, April 11, 2014

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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."

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.

Kevin Mayer

Friday, April 11, 2014

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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.

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.”

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.



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Cancer Personalized Medicine: What You Need to Know 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 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 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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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.