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Issue link: https://clinicalomics.epubxp.com/i/853204
28 Clinical OMICs July/August 2017 www.clinicalomics.com testing for patients while bringing the power of NGS-based diagnostics to any doctor who wants to order one. "If you are a patient in the middle of the country and aren't lucky enough to be near one of the premier medical centers, you are going to get a very different level of care ,and that starts with the diagnostic test," he said. "So this is the field moving in the right direction." Rare Disease Diagnosis NGS has also made a broad impact in the diagnosis of Men- delian diseases, a field that for many years was more miss than hit, and often relied on a doctor 's intuition, luck, or a little of both in order to make a positive diagnosis. "It has completely changed the field of genetics," said David Bick, M.D., faculty investigator and chief medical officer of HudsonAlpha Institute's Smith Family Clinic for Genomic Medicine. "We started out just looking at one gene at a time. Then we looked at groups of genes. But next-gen- eration sequencing allows you to look at large groups of genes and do it cost effectively. We are rapidly reaching the point where we will do whole-genome sequencing on any- body you think has a rare disease." A significant contributor in diagnosing rare diseases are methods to share data on rare variants with other doctors and researchers worldwide. Publicly available databases like ClinVar, which contains data on human genetic vari- ation and phenotypes, and Matchmaker Exchange, which allows participating institutions and doctors to compare the phenotype and genotype of their patients against data from a variety of sources such as DECIPHER from the Well- come Trust Sanger Institute and matchbox from the Broad, provide doctors with access to ever-growing sets of data on rare variants. With the costs decreasing, NGS for whole-genome sequencing is playing an increasing role in rare disease diagnosis. "I would argue that the large-scale sequencing efforts that are available today have made major changes in our ability to clinically diagnose the patient," said Heidi Rehm, Ph.D., a researcher with the Broad Institute and a driving force behind ClinVar and other phenotype-genotype data-shar- ing initiatives (see story page 12). "But one critical piece of that is in order to interpret variations you need incredibly large reference populations to compare your case data to." Dealing with Data If more data will ultimately lead to more answers for treat- ing rare diseases and cancer, then the increased use of NGS due to its plummeting cost is fueling the exponential growth of the raw materials needed for more precise diag- noses. But with a single whole genome comprising more than 700 megabyte of data and significant individual public and private efforts to sequence hundreds of thousands and evens millions of genomes, effectively handling and analyz- ing that data is no trivial matter. Further, finding effective ways of presenting the data to doctors—most of whom are not experienced in reading and interpreting genomic data—that can aid them in making a diagnosis or creating a treatment plan is paramount. "We first have to enable the physicians to incorporate the data," said Mirza Cifric, cofounder and CEO of Veritas Genetics. "This notion that we throw a 500-page report over the wall to an already overworked and stretched-thin phy- sician will not make us any friends. That thing that gets lost in that type of approach is the tremendous value that this information can and may have to an individual patient. We have to reconcile that." Many in the industry recognize that NGS technology has matured and generating sequencing data is becoming stan- dard practice. "I don't think the technology is the issue anymore. It has become fairly standardized and routine. I think the inter- pretation is still the hardest component of this," said Devin Absher, Ph.D., faculty member of HudsonAlpha Institute. "So it is really how do you take that data, integrate it, and provide the clinical decision support for that oncologist who may not have a lot of experience with sequencing data (continued from previous page) U.S. Air Force / Kemberly Groue Molecular technologist DeShannon Hall uses a robotic sample prep handler at the Air Force Medical Genetics Center. The center is focused on providing clinical and laboratory diagnostic services to support Department of Defense facilities worldwide.