Abstract 2608: Global integration of knowledgebases for clinical interpretation of cancer variants

Abstract

Abstract The paradigm of precision medicine envisions a future in which a cancer patient’s molecular information can be interpreted in the context of accumulated knowledge to inform diagnosis, prognosis and treatment options most likely to benefit that individual patient. Accordingly, many groups have created knowledgebases to annotate cancer genomic mutations associated with evidence of pathogenicity or relevant treatment options. However, in real-life practice, clinicians and researchers are unable to utilize the accumulated knowledge derived from such efforts. Integration of the available knowledge is currently infeasible because each group (often redundantly) curates their own knowledgebase without adherence to any interoperability standards. Therefore, there is a clear need to standardize and coordinate clinical-genomics curation efforts, and create a public community resource able to query the aggregated information. To this end we have formed the Variant Interpretation for Cancer Consortium (VICC) as part of the Global Alliance for Genomic Health (GA4GH) to bring together the leading institutions that are independently developing comprehensive cancer variant interpretation databases. VICC participants share a desire to coordinate efforts and thus enhance the value of each independent effort. Each participant has agreed to: (1) sharing at least a minimal set of required data elements for cancer variant interpretations; (2) Protecting patient privacy by focusing on only clinical interpretations of variants derived from published findings, not individual patient/variant-level observations, thus avoiding the possibility of linking variants to individuals; (3) Sharing all or a significant proportion of interpretations accumulated by their ongoing curation efforts; (4) Releasing content under a permissive license (free and non-exclusive for research use); (5) Releasing software in public repositories with open source licenses; (6) Making data available through publicly accessible and documented APIs and as cross-knowlegebase bulk downloads; and (7) Using, the existing schemas, APIs and demonstration implementations developed by GA4GH. To date a large number of academic and commercial groups have agreed to participate including those at Washington University (CIViC), MSKCC (OncoKB), Weill Cornell (PMKB), Oregon Health and Science University, Dana-Farber, Institute for Research in Biomedicine, Illumina Inc, and others. Additional participants are welcome (http://ga4gh.org/#/vicc). We will present progress by the VICC to create a federated query service able to interrogate associations between cancer gene alterations and clinical actions, for each cancer disease setting, based on evidence amassed from all participating institutions world-wide. Citation Format: Obi L. Griffith, Malachi Griffith, David Tamborero, Alex H. Wagner, Kilannin Krysiak, Catherine Del Vecchio Fitz, Debyani Chakravarty, Ethan Cerami, Olivier Elemento, Nikolaus Schultz, Adam Margolin, Nuria Lopez-Bigas. Global integration of knowledgebases for clinical interpretation of cancer variants [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2608. doi:10.1158/1538-7445.AM2017-2608