Molecular Profiling (MP) Core G

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SUMMARY/ABSTRACT: Molecular Profiling Core G The goals of the Molecular Profiling Core (MP) Core G are to (a) perform the duties of the study-wide biobank including tracking and distribution of samples to Project 3 and other Cores and Projects as needed, (b) facilitate the rapid public sharing of biospecimens through NCRAD (National Centralized Repository for Alzheimer’s Disease and Related Dementias) by providing them with twice yearly sample shipments for deposition and administration to the general scientific community, (c) generate molecular data for biospecimens collected from Projects 1 and 2, (d) provide iterative re-analysis of genomic data (RNA and DNA) as necessitated by the activities of Project 4 to ensure that all study data is up-to-date with regards to their respective analytical and annotation pipelines, and (e) provide expert consultation on all aspects of biomarker discovery and development to the Precision Aging Network (PAN) investigators. Project 1 biospecimens will consist of 10,000 dried blood spot cards (DBS). These DBS samples are self- collected from the nationally distributed cohort of individuals who participate in the MindCrowd-Expanded (MC-Expanded) cohort. The MP Core will perform APOE and array-based genotyping on these specimens and deposit the raw and processed data into the study data repository via the Data Science (DS) Core. These data will be utilized by Project 1 investigators to identify genetic risk factors that are associated with, or that modify, cognitive performance on the MC-Expanded test battery. Additionally, through the use of the genome- wide array data, each participant will be assigned individualized polygenic risk score (PRS) pertaining to the various risk factors detailed in Project 2 (e.g., Alzheimer’s disease, hypertension, diabetes, sleep, etc.). Project 2 biospecimens will consist of 1,620 plasma, serum, and CSF samples collected from the face-to-face characterized cohort. Several molecular profiling datasets will be generated from these samples including; whole genome sequencing, CSF biomarkers, immune and inflammatory measurements, pan-viral exposures, T- and B-cell receptor repertoires, whole blood and cell-free exosome RNA sequencing, and Horvath epigenetic clock determinations among others (detailed further in the MP Core). These data will be quality controlled and uploaded to the study data repository in both raw and processed formats for use by investigators in the Projects and Cores. The acquired high-quality and wide-ranging molecular data will play significant roles in answering major research questions in our proposed projects, and can also be used by the national research community studying cognitive aging, Alzheimer’s disease (AD), and related dementias (ADRD).