54. Creation of a knowledgebase of high-quality assertions of the clinical actionability of somatic variants in cancer

Abstract

Interpretation of the clinical significance of somatic variants in cancer remains a major challenge for cancer diagnosis, prognosis, and predicting response to targeted therapies. The Clinical Genome Resource (ClinGen) has established tools, web resources and procedures to help communities of experts establish the clinical relevance of genes and variants. However, ClinGen's effort is almost exclusively focused on the interpretation of germline variants and their role in heritable phenotypes, leaving a significant gap in clinical interpretation of somatic variants in cancer. To address this need, the ClinGen Somatic Clinical Domain Working Group is creating a knowledgebase of high-quality assertions of the clinical significance of somatic variants in cancer within the CIViC platform to capture expert panel curation efforts and adapts the procedures of ClinGen germline groups to somatic variant interpretation. This effort will broadly enable research and clinical translation involving the use of somatic cancer variant knowledge. We have established processes to engage an expert community and facilitated the creation of eight Somatic Cancer Variant Curation Expert Panels (SC-VCEPs) with strategies to foster necessary expansion. Formation of these SC-VCEPs supports the creation of a ClinGen Somatic Knowledgebase of clinical cancer variant assertions curated and approved by experts. We are working to adopt and guide ongoing development of several emerging GA4GH standards that enable the Findable, Accessible, Interoperable, and Reusable (FAIR) principles for genomic knowledge sharing. Finally, we are using natural language processing approaches to accelerate a set of defined human knowledge curation tasks that currently limit the rate of expert curation.