Baylor College of Medicine/Stanford University Clinical Genome Resource (CLINGEN)

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Project Summary/Abstract The Clinical Genome Resource (ClinGen) is an essential community resource developing clinically relevant genomic knowledge. Three research teams at Harvard/Geisinger, UNC/Kaiser and Baylor College of Medicine/Stanford have worked collaboratively since 2013 to create successful frameworks and software systems for sustained curation of the human genome. The landmark achievement in 2018 of FDA recognition as the first Public Human Genetic Variant Database significantly increased ClinGen's prominence as an innovative genome curation program. ClinGen's strategy has been highly successful: creating the training, framework and oversight for international expert panels (over 1400 members), while generating dynamic user- informed public tools including the ClinGen Curation Interfaces, Allele Registry and Linked Data Hub. This multi- institutional application from Baylor College of Medicine and Stanford University in response to PAR-20-100 Genomic Community Resources to support our ongoing development of the innovative advanced web technologies for software infrastructure that supports ClinGen’s gene, variant and actionability curation efforts. In this application we seek to operate at scale, generating procedures and informatics for high-throughput curation across ClinGen domains. We propose multiple improvements to scale our work through streamlined aggregation and linking of genomic and phenotypic data including sources from diverse populations (Aim 1) semi-automation for gene and variant curation (Aim 2) and actionability curation (Aim 3). We anticipate new facets of clinical genomics including standards for variant classification in hereditary and somatic cancer, forging novel curation approaches including curation of polygenic risk scores (PRS) and modeling curation of complex disorders in HLA-related rheumatologic and autoimmune diseases (Aim 4). We have developed innovative frameworks for appropriate use of ancestry and diversity in clinical genomics, while in parallel working to expand the diversity of the ClinGen workforce and users of ClinGen curated knowledge (Aim 5).