Core B is proposed to provide three separate but highly integrated functions, including: 1) Standardized sample processing, genotyping, and immunophenotyping; 2) Reliable, secure, high-quality specimen storage within the UFDI Study Bank with efficient distribution of samples to investigators; and 3) Functional genomics analyses using both biostatistical and bioinformatic approaches, with this latter Aim representing a new feature of this Core to support program-wide syngergy and productivity. Specifically, Core B will ensure that high-quality peripheral blood specimens are promptly processed to serum, plasma, mononuclear cells (PBMC), and DNA through adherence to established Standard Operating Procedures (SOPs). These samples, as well as induced pluripotent stem cell (iPSC) lines and gene-edited primary human T cells generated by Projects 2 & 3, respectively, are stored according to biobanking best practices with barcoded sample tracking as well as emergency response planning by trained staff. The samples and associated data will be securely managed using our internal database (Diabase, managed by Core A) that together, tracks sample provenance from the point of patient consent, through sample and clinical metadata intake, and ultimately, Project data deposition. For all study specimens, this Core will also continue to perform a series of well-validated assays for immunologic (islet autoantibodies [AAb] against GAD, IA-2, ZnT8, and insulin; type 1 interferon [T1-IFN] levels using HEK-Blue reporter cells, complete blood count [CBC], and extensive human immunophenotyping [HIP] by spectral flow cytometry), metabolic (glucose and HbA1C levels), emerging biomarker (exocrine pancreas enzymes), and genetic characterization (precision medicine genotyping via our custom Axiom array involving >790K single nucleotide polymorphism [SNPs]; the UFDIchip). The UFDIchip provides genome-wide coverage for four-digit HLA resolution, genetic ancestry imputation, calculation of polygenic genetic risk scores (GRS) for type 1 diabetes (T1D), as well as interrogation of known and emerging risk variants. Importantly, these assays will be performed following clinical laboratory standards, through participation in national/international programs to assure QA/QC. For example, the Core's performance in the International Autoantibody Standardization Program (IASP) consistently scores with high sensitivity and specificity. With this, Core B will provide Projects 1, 2 & 3 with uniformly processed samples as well as standardized, high-content, FAIR-compliant datasets that are highly relevant to the research proposed, in order to optimize multivariable analysis of data generated across the Program. The UFDI Data Science Team will implement R packages and Shiny applications for pre-processing, analysis, and integration of single cell multi-omics, high-parameter imaging, and in vitro functional data generated through the three Projects. Core B will continue to facilitate sharing of...