A genomic data archive from the Network for Pancreatic Organ donors with Diabetes

Abstract

The Network for Pancreatic Organ donors with Diabetes (nPOD) is the largest biorepository of human pancreata and associated immune organs from donors with type 1 diabetes (T1D), maturity-onset diabetes of the young (MODY), cystic fibrosis-related diabetes (CFRD), type 2 diabetes (T2D), gestational diabetes, islet autoantibody positivity (AAb+), and without diabetes. nPOD recovers, processes, analyzes, and distributes high-quality biospecimens, collected using optimized standard operating procedures, and associated de-identified data/metadata to researchers around the world. Herein describes the release of high-parameter genotyping data from this collection. 372 donors were genotyped using a custom precision medicine single nucleotide polymorphism (SNP) microarray. Data were technically validated using published algorithms to evaluate donor relatedness, ancestry, imputed HLA, and T1D genetic risk score. Additionally, 207 donors were assessed for rare known and novel coding region variants via whole exome sequencing (WES). These data are publicly-available to enable genotype-specific sample requests and the study of novel genotype:phenotype associations, aiding in the mission of nPOD to enhance understanding of diabetes pathogenesis to promote the development of novel therapies.

Transplantation: platform to study recurrence of disease

“…nPOD as an organization recovers, processes, analyzes and distributes high quality biospecimens to researchers around the world. nPOD recently published a genomic data archive to promote "the study of novel genotype:phenotype associations, aiding in the mission of nPOD to enhance understanding of diabetes pathogenesis" and to promote the development of novel therapies (35). We hope that our T1DR contributions will help to achieve the goal of new, effective therapies for T1D.…”

Diabetes Study of Children of Diverse Ethnicity and Race: Study design

“…In addition, we will collect blood samples for DNA extraction/purification for SNP genotyping (for GRS calculation and genetic ancestry imputation 84 ) and serum for measurement of islet autoantibodies (GADA, IA-2A, and ZnT8A). C-peptide and glucose will also be measured in non-fasting conditions, which provides good discrimination between T1D and T2D, 32,[85][86][87][88][89][90][91][92] and may facilitate the future translation to clinical practice.…”

“…We will control for ancestry in all models with the first 5-10 principal components of ancestry. 84 Principal components will be added to the F I G U R E 1 Schematic summary of Diabetes Study of Children osf Diverse Ethnicity and Race (DISCOVER) study. Abbreviations: AA, African American/Black; BP, Blood pressure; Cpep, C-peptide; DM: Diabetes mellitus; EMR, Electronic medical records; GA, Georgia (U.S.A.); GRS, Genetic risk score; Hisp, Hispanic/Latino; SNP, Single nucleotide polymorphism; T1D, Type 1 diabetes; T2D, Type 2 diabetes; TX, Texas (U.S.A.); y/o, Years old.…”

“…From peripheral blood samples, DNA will be extracted and purified for subsequent SNP analysis at the University of Florida Diabetes Institute (UFDI) Immune Monitoring Core using a customised Affymetrix Axiom microarray (UFDIchip 84 ) with >985K SNPs. This chip includes ancestry informative markers as well as SNPs for HLA and non-HLA SNPs that are part of, allow reliable imputation of, and/or are in high linkage disequilibrium (LD) with the T1D GRS1, GRS2, and AA-GRS.…”

Modeling type 1 diabetes progression using machine learning and single-cell transcriptomic measurements in human islets

“…In this work, we evaluated the feasibility of modeling early molecular events in tissues relevant to the etiology of T1D using machine learning and single-cell transcriptomic maps of individual cells from pancreatic tissues. The JDRF-supported nPOD 7 and the NIDDK-supported HPAP consortia 8 , 9 are ongoing efforts, collecting pancreatic tissues and immune-related organs from hundreds of controls, non-diabetic but islet AAb-positive (AAb+), and T1D organ donors. Among numerous genomics and molecular assays, the revolutionizing single-cell transcriptomics (single-cell RNA sequencing [scRNA-seq]) has become a standard technology to study T1D development.…”