A harmonized meta-knowledgebase of clinical interpretations of somatic genomic variants in cancer.
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
25
04
2019
accepted:
26
02
2020
pubmed:
5
4
2020
medline:
27
6
2020
entrez:
5
4
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32246132
doi: 10.1038/s41588-020-0603-8
pii: 10.1038/s41588-020-0603-8
pmc: PMC7127986
doi:
Types de publication
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
448-457Subventions
Organisme : NCI NIH HHS
ID : U24 CA237719
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA231844
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NIH HHS
ID : R24 OD011883
Pays : United States
Organisme : Medical Research Council
Pays : United Kingdom
Organisme : NHGRI NIH HHS
ID : U41 HG009649
Pays : United States
Organisme : NHGRI NIH HHS
ID : U41 HG009650
Pays : United States
Organisme : NCI NIH HHS
ID : F32 CA206247
Pays : United States
Organisme : Cancer Research UK
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : R01 CA180778
Pays : United States
Organisme : NHGRI NIH HHS
ID : R00 HG007940
Pays : United States
Organisme : NHGRI NIH HHS
ID : K99 HG010157
Pays : United States
Organisme : NHGRI NIH HHS
ID : U41 HG006834
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA217862
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG007437
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA209936
Pays : United States
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