Documents & Announcements

A harmonized meta-knowledgebase of clinical interpretations of cancer genomic variants

Alex H Wagner, Brian Walsh, Georgia Mayfield, David Tamborero, Dmitriy Sonkin, Kilannin Krysiak, Jordi Deu Pons, Ryan Duren, Jianjiong Gao, Julie McMurry, Sara Patterson, Catherine Del Vecchio Fitz, Ozman Ugur Sezerman, Jeremy Warner, Damian T Rieke, Tero Aittokallio, Ethan Cerami, Deborah Ritter, Lynn M Schriml, Melissa Haendel, Gordana Raca, Subha Madhavan, Michael Baudis, Jacques S Beckmann, Rodrigo Dienstmann, Debyani Chakravarty, Xuan Shirley Li, Susan Mockus, Olivier Elemento, Nikolaus Schultz, Nuria Lopez-Bigas, Mark Lawler, Jeremy Goecks, Malachi Griffith, Obi L Griffith, Adam Margolin

Precision oncology relies on the accurate discovery and interpretation of genomic variants to enable individualized therapy selection, diagnosis, or prognosis. However, knowledgebases containing clinical interpretations of somatic cancer variants are highly disparate in interpretation content, structure, and supporting primary literature, reducing consistency and impeding consensus when evaluating variants and their relevance in a clinical setting. With the cooperation of experts of the Global Alliance for Genomics and Health (GA4GH) and of six prominent cancer variant knowledgebases, we developed a framework for aggregating and harmonizing variant interpretations to produce a meta-knowledgebase of 12,856 aggregate interpretations covering 3,437 unique variants in 415 genes, 357 diseases, and 791 drugs. We demonstrated large gains in overlapping terms between resources across variants, diseases, and drugs as a result of this harmonization. We subsequently demonstrated improved matching between patients of the GENIE cohort and harmonized interpretations of potential clinical significance, observing an increase from an average of 34% to 57% in aggregate. We developed an open and freely available web interface for exploring the harmonized interpretations from these six knowledgebases at

Date July 11, 2018
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