1084-OR: PanKbase Integrated Pancreatic Islet Single-Cell Map: A Comprehensive Resource with New Insights into Diabetes

Introduction and Objective: Single-cell (SC) gene expression analysis of pancreatic islets from donors with and without diabetes provides key insights into disease development and heterogeneity. Creating a large atlas through uniform dataset harmonization is essential to overcome challenges such as limited islet availability and inconsistent metadata, experimental methods, and analysis standards. Methods: Sequencing reads generated and/or provided by three independent islet sources (Human Pancreas Analysis Program, Integrated Islet Distribution Program, and Prodo Labs), were collected and aligned. Genotypes and donor metadata were verified to ensure accurate sample identity. Rigorous quality control was employed to select high-quality reads and cells, minimize ambient RNA contamination, and eliminate doublets. During integration, we accounted for key variables such as age, sex, BMI, islet distributor, and sequencing chemistry. Differential expression analysis (DEA) was performed using a latent variable approach. Results: Our comprehensive islet SC atlas combines data from 191 samples across 140 donors (59 female, 81 male), making it the largest number of donors available to date. It represents five phenotypes: 69 non-diabetic, 12 autoantibody-positive non-diabetic, 11 pre-diabetic, 12 T1D, and 36 T2D. It maps 448,935 cells into 13 distinct populations, including alpha cells (43% of total cells), beta (27%), and smaller groups such as immune (0.6%). DEA of the six most abundant cell types revealed 1,805 genes differentially expressed (FDR 5%), of which 1,402 are novel, between T1D and non-diabetic samples, enriching for pathways such as “adaptive immune response” and “Type I diabetes mellitus”. A notable novel T1D-up-regulated gene in beta cells is OPLAH, which is involved in the glutathione pathway. Conclusion: By integrating data across 191 samples, we created a comprehensive SC map of pancreatic islets, available at www.pankbase.org, and enabled research into diabetes mechanisms and progression. Disclosure H.T. Vu: None. H. Sun: None. S.A. Sharp: None. P. Kudtarkar: None. L. Brusman: None. Y. Wang: None. R. Mao: None. F. Feng: None. S. Corban: None. A.K. Huber: None. J. Jurgens: None. T. Bate: None. D. Jang: None. C.C. Robertson: None. P. Smadbeck: None. Y. Sun: None. M. Brandes: None. J. Liu: None. S. Chen: Stock/Shareholder; Current; iOrganBio Inc. Stock/Shareholder; Ended; Oncobeat. J. Cartailler: None. B.F. Voight: Other - Invited speaker for seminar; They covered expenses (Travel, lodging, food) for the visit.; Ended; Eli Lilly and Company. M. Brissova: None. A.L. Gloyn: Speaker's Bureau; Ended; Novo Nordisk. Other - Spouse is an employee and holds stock options in Roche; Current; Genentech, Inc. K. Gaulton: Other - Spouse employee; Current; Altos Labs. Stock/Shareholder; Current; Neurocrine Biosciences, Inc. S. Parker: Research Support; Current; Pfizer Inc. Consultant; Ended; Novo Nordisk. Funding NIDDK (U24DK138515, U24DK138512)