1269-P: The Type 1 Diabetes Knowledge Portal: An Open-Access Resource for Insights into the Genetic and Genomic Basis of Type 1 Diabetes

Abstract

Type 1 diabetes (T1D) is a complex disease and more than 100 genetic loci influencing T1D risk have been identified to date. Discovering the genes and biological mechanisms through which these variants impact T1D requires the integration of multiple data types. We have created the T1D Knowledge Portal (T1DKP; type1diabetesgenetics.org) to help researchers utilize genetic and functional genomic data to generate hypotheses about the genes involved in T1D and its complications. The T1DKP aggregates genetic association data from the T1D community along with relevant functional genomics (e.g., accessible chromatin, 3D conformation, gene expression, gene perturbation) data, which are loaded via a sister resource, the Common Metabolic Diseases Genome Atlas (cmdga.org) . Using the HuGeAMP software platform developed for the Common Metabolic Diseases Knowledge Portal (CMDKP; cmdkp.org) within the Accelerating Medicines Partnership for Common Metabolic Diseases, the T1DKP integrates data by applying bioinformatic methods such as meta-analysis of genetic association results to generate “bottom-line” p-values, enrichment of genetic association within tissue-specific genomic annotations, and more. Interactive visualizations allow the user to explore results and to perform custom, on-the-fly analyses. The T1DKP also includes expert-curated lists of predicted effector genes of T1D loci, displaying the supporting evidence behind each prediction. Since the T1DKP is nested within and built upon the same framework as the CMDKP, users may navigate seamlessly to see results relevant to other metabolic disorders. In total the T1DKP project aims to accelerate our understanding and treatment of T1D by providing decision support for researchers as they prioritize loci, variants, and genes for experimental study. Disclosure M.C.Costanzo: Other Relationship; Pfizer Inc. P.V.Kudtarkar: None. U.Nayak: None. S.Onengut-gumuscu: None. Y.Sun: None. S.S.Rich: None. J.Flannick: None. K.J.Gaulton: Consultant; Genentech, Inc., Stock/Shareholder; Neurocrine Biosciences, Inc., Vertex Pharmaceuticals Incorporated. N.Burtt: n/a. Funding National Institutes of Health (5UM1DK105554-07)