Omics Core

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SUMMARY The Omics core (Core 2) will support the overall U19 proposal by generating multiple layers of omics data from biospecimens collected as part of the well characterized cohorts of ADNI, MCSA and 5 ADRCs (Mayo Clinic, Indiana University, 1Florida, University of Michigan and Washington University). Multiple biospecimens have been, or will be, collected for each of the proposal projects. These include matched post-mortem brain tissue and ante-mortem blood (P1), or multiple blood tubes collected longitudinally (P2, P3), to identify molecular changes related to the rich phenotypic (pathology, imaging, clinical, biomarker) data on the same individuals. Data will be collected on diverse cohorts representing non-Hispanic white, Latino American and African American (NHW, LA and AA) populations. Omics measures proposed to be collected include bulk total RNA sequencing, from brain tissues and PAXgene blood, single nucleus RNA sequencing (snRNASeq) from brain tissues, proteome from brain tissues and plasma, metabolome and lipidome from brain tissues and serum, DNA methylation from brain tissues and blood and genotype arrays from brain tissue. These measures will provide the molecular profiles on which the project hypotheses will be tested. The Omics core will support the project aims, and provide harmonized omics data by providing centralized coordination of biospecimen management, innovative study design and harmonized generation of multi-omics data. Furthermore, comprehensive documentation related to biospecimen collection, handling, and omics data generation approaches, which will contribute to the open science goals of the overall U19 program, will be provided to the Administrative core (C1). Batch effects related to sample collection, processing, storage and transfer will be accounted for and minimized to enable the integrative analysis goals of the projects and the Analytic core (C3). The Omics core will address the unique challenges of integrating large scale omics data collection by providing centralized study design for these key processes in consultation with each of the projects and the Analytic core. Protocols have been and will continue to be harmonized in collaboration with study coordinators from each of the relevant participating sites. The Omics core has 3 specific aims to address the needs of the proposal: (1) Coordinate the collection, storage and distribution of biospecimens for omics studies; (2) Generate high-quality omics data harmonized across study sites, tissues and cohorts; (3) Provide comprehensive biospecimen and omics documentation to facilitate data sharing within and outside the U19 program. Through these efforts, we expect to generate the proposed harmonized omics measures (RNAseq, snRNAseq, Proteome, Metabolome, Lipidome, DNA methylation array and genotype array), with appropriate detailed documentation. These data will be provided to the U19 investigators and the broader research community to enable analysis and identification of centrally- linked longitudinal peripheral molecular signatures.