CLINICAL CORE: PROJECT SUMMARY The Clinical Core will be led by Ramnik Xavier (Director), Andrew Chan (Co-Director), and Ashwin Ananthakrishnan (Technical Director). Core services are organized into (1) consultation, training, and education, including advice on research study design, execution, and analysis as well as education and training of junior investigators, residents, and fellows; (2) biospecimen services, including clinical database and patient identification, biospecimen collection and processing, and serum, stool, and tissue biorepository services; (3) data collection and analysis, including regulatory services, a genotype and microbiome library, RNA-sequencing from colonic biopsies, and bioinformatics support; and (4) access to a clinical and translational database, including detailed phenotyping and clinical data linked to each patient’s genotype and microbiome features. Central components of the Clinical Core are two patient cohorts: the Prospective Registry in IBD Study at MGH (PRISM) and the GI Disease and Endoscopy Registry (GIDER). By obtaining pre- and post-event samples, these cohorts are anchored around disease extension, new diagnosis, and institution of specific biologic treatments that provide evolving clinical metadata and serial biospecimens. With more than 3,200 patients enrolled, PRISM now collects biospecimens for metagenomic, metatranscriptomic, and metabolomic analyses as well as information on early life environmental exposures, fatigue, depression, and diet. The Core recently introduced GIDER, a longitudinal colonoscopy-based cohort with 800 healthy individuals enrolled to date that will enhance our understanding of genetic, microbial, and environmental determinants across a spectrum of gastrointestinal diseases. This core serves as a hub for interactions between clinicians and basic researchers, allowing scientists to test hypotheses in human samples and clinicians to gain valuable insight into disease states. The specific aims of the Clinical Core are to (1) build a biorepository of patients with Crohn’s disease and ulcerative colitis with accurate phenotyping of disease as well as sampling of blood, stool, urine, and tissue in various disease states (active/inactive disease) and related to various therapeutic and environmental perturbations; (2) develop and expand longitudinal cohorts of health and disease anchored around disease diagnosis, prediction of relapse, and response to specific therapies in patients with IBD; (3) define the phenotypic implications of genetic loci and microbial perturbations with regard to clinical manifestations, response to therapy, and to examine the interaction with the environment; (4) facilitate education and training in research by providing consultations regarding study design, methods, and analysis as well as attract new investigators to the field through these services; and (5) translate laboratory and clinical research findings into interventions that improve diagnosis, deve...