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

Details

Serval ID
serval:BIB_20B4C06420B1
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A harmonized meta-knowledgebase of clinical interpretations of somatic genomic variants in cancer.
Journal
Nature genetics
Author(s)
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.
Working group(s)
Variant Interpretation for Cancer Consortium
ISSN
1546-1718 (Electronic)
ISSN-L
1061-4036
Publication state
Published
Issued date
04/2020
Peer-reviewed
Oui
Volume
52
Number
4
Pages
448-457
Language
english
Notes
Publication types: Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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.
Keywords
Databases, Genetic, Diploidy, Genetic Variation/genetics, Genomics/methods, Humans, Knowledge Bases, Neoplasms/genetics, Precision Medicine/methods
Pubmed
Web of science
Open Access
Yes
Create date
06/07/2020 14:15
Last modification date
20/01/2021 6:26
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