Healthcare magazine for research scientists, labs, pathologists, hospitals, cancer centers, physicians and biopharma companies providing news articles, expert interviews and videos about molecular diagnostics in precision medicine
Issue link: https://clinicalomics.epubxp.com/i/853204
www.clinicalomics.com July/August 2017 Clinical OMICs 15 ordering sites and here is the list of minimum require- ments you must meet to be on this list. I wasn't sure exactly what the response from the lab- oratories would be, but I got incredible support. From those that didn't meet the criteria, I got several emails that said they are working diligently on getting it accomplished. They have gone to leadership and have gotten buy-in from their company executives and they are going to get this done.That was very gratifying and I'm very optimistic about the future. Aside from ClinVar, what else are you working on? HR: Another challenge we have, parallel to variant interpre- tation, is gene interpretation—what are the genes that when you disrupt them actually lead to disease pheno- types. This turns out not to be as straightforward as you might think. There are genes that anyone, off the top of their head, know are disease genes, like BRCA1 and BRCA2 are breast cancer genes, and CFTR is the cystic fibrosis gene. Then you start to get down to a layer of one paper where somebody claimed a mutation in [one] gene is associ- ated with [a specific] condition, but the data is not that strong. The claims about disease genes are what lead clinical labs to put these genes into their tests. This is a major issue. And now we are embarking on a systematic curation of all claimed gene–disease associa- tions through ClinGEN. At the recent ClinGEN meeting [there was] a commitment to share in this activity as a group and to get all of these 5,000 or 6,000 genes curated systematically to define the level of evidence. We have published a paper from ClinGEN that is the scoring framework to define strength of evidence of each gene that is the basis by which we will do this. We also have a project that relates to this. A lot of these genes that we review end up in this 'limited' bucket where there is insufficient evidence to implicate them as a true disease gene, but it is still right for discovery. I'm also in charge of a project called Matchmaker Exchange. We have developed a federated network of rare disease databases used in gene-discovery efforts. When you find the candidate gene in a patient with a disease, but you have insufficient evidence to implicate it, through this federated network you can query all of the other databases to find patients whose phenotype matches and have a candidate mutations in the same gene to bring those cases together and implicate the gene. That is a major project that we have been working on for the last few years and is really growing quickly. Mark Ostow