A harmonized meta-knowledgebase of clinical interpretations of somatic genomic variants in cancer Journal Article

   


Authors: Wagner, A. H.; Walsh, B.; Mayfield, G.; Tamborero, D.; Sonkin, D.; Krysiak, K.; Deu-Pons, J.; Duren, R. P.; Gao, J.; McMurry, J.; Patterson, S.; Del Vecchio Fitz, C.; Pitel, B. A.; Sezerman, O. U.; Ellrott, K.; Warner, J. L.; Rieke, D. T.; Aittokallio, T.; Cerami, E.; Ritter, D. I.; Schriml, L. M.; Freimuth, R. R.; Haendel, M.; Raca, G.; Madhavan, S.; Baudis, M.; Beckmann, J. S.; Dienstmann, R.; Chakravarty, D.; Li, X. S.; Mockus, S.; Elemento, O.; Schultz, N.; Lopez-Bigas, N.; Lawler, M.; Goecks, J.; Griffith, M.; Griffith, O. L.; Margolin, A. A.; Variant Interpretation for Cancer Consortium
Article Title: A harmonized meta-knowledgebase of clinical interpretations of somatic genomic variants in cancer
Abstract: Precision oncology relies on accurate discovery and interpretation of genomic variants, enabling individualized diagnosis, prognosis and therapy selection. We found that six prominent somatic cancer variant knowledgebases were highly disparate in content, structure and supporting primary literature, impeding consensus when evaluating variants and their relevance in a clinical setting. We developed a framework for harmonizing variant interpretations to produce a meta-knowledgebase of 12,856 aggregate interpretations. We demonstrated large gains in overlap between resources across variants, diseases and drugs as a result of this harmonization. We subsequently demonstrated improved matching between a patient cohort and harmonized interpretations of potential clinical significance, observing an increase from an average of 33% per individual knowledgebase to 57% in aggregate. Our analyses illuminate the need for open, interoperable sharing of variant interpretation data. We also provide a freely available web interface (search.cancervariants.org) for exploring the harmonized interpretations from these six knowledgebases.
Journal Title: Nature Genetics
Volume: 52
Issue: 4
ISSN: 1061-4036
Publisher: Nature Publishing Group  
Date Published: 2020-04-01
Start Page: 448
End Page: 457
Language: English
DOI: 10.1038/s41588-020-0603-8
PUBMED: 32246132
PROVIDER: scopus
PMCID: PMC7127986
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85083041229&doi=10.1038%2fs41588-020-0603-8&partnerID=40&md5=3490ff7e92a0861dcf4cb6093fa0ada3
Notes: Article -- Export Date: 1 May 2020 -- Source: Scopus
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MSK Authors
  1. Debyani Chakravarty
    87 Chakravarty
  2. Jianjiong Gao
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  3. Nikolaus D Schultz
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