72. What's under VarCat's hat: Modeling variant oncogenicity classifications with GA4GH Standards

Abstract

The Variation Categorizer (VarCat) is a tool for classifying variant oncogenicity for variant-disease pairings in a clinical laboratory workflow. VarCat implements the ClinGen/CGC/VICC oncogenicity guidelines to assist in the classification of a variant's capability for driving cancer formation and growth. VarCat provides an intuitive interface for structured data sharing and produces classification assessments compliant with genomic knowledge standards specified by the Global Alliance for Genomics and Health (GA4GH).

Here, we present the models, structures, and capabilities provided by VarCat's API and demonstrate its ability to create standardized assessments. VarCat leverages harmonized data from several genomic knowledge sources collated by the VICC MetaKB service. VarCat ensures comprehensive analysis by incorporating standardized gene, variant, therapeutic, disease, and evidence data, and it is driving the development of GA4GH genomic knowledge formats for oncogenicity data. We also describe the suite of normalization microservices used by MetaKB and VarCat to harmonize genomic knowledge concepts. We illustrate how VarCat reduces barriers to interoperable variant-associated evidence through the adoption of the GA4GH Variation Representation Specification (VRS). We also present standardized evidence data using the AMP/ASCO/CAP guidelines for clinical actionability. Overall, our work illustrates how GA4GH Genomic Knowledge Standards drive data interoperability and successful knowledge exchange, ultimately enhancing genetic disease comprehension and advancing patient care.