RT Journal Article
SR Electronic
T1 A harmonized meta-knowledgebase of clinical interpretations of cancer genomic variants
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 366856
DO 10.1101/366856
A1 Alex H Wagner
A1 Brian Walsh
A1 Georgia Mayfield
A1 David Tamborero
A1 Dmitriy Sonkin
A1 Kilannin Krysiak
A1 Jordi Deu Pons
A1 Ryan Duren
A1 Jianjiong Gao
A1 Julie McMurry
A1 Sara Patterson
A1 Catherine Del Vecchio Fitz
A1 Ozman Ugur Sezerman
A1 Jeremy Warner
A1 Damian T Rieke
A1 Tero Aittokallio
A1 Ethan Cerami
A1 Deborah Ritter
A1 Lynn M Schriml
A1 Melissa Haendel
A1 Gordana Raca
A1 Subha Madhavan
A1 Michael Baudis
A1 Jacques S Beckmann
A1 Rodrigo Dienstmann
A1 Debyani Chakravarty
A1 Xuan Shirley Li
A1 Susan Mockus
A1 Olivier Elemento
A1 Nikolaus Schultz
A1 Nuria Lopez-Bigas
A1 Mark Lawler
A1 Jeremy Goecks
A1 Malachi Griffith
A1 Obi L Griffith
A1 Adam Margolin
YR 2018
UL http://biorxiv.org/content/early/2018/07/11/366856.abstract
AB 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 search.cancervariants.org.