Omics Core

摘要 OMICS核心(核心2)将通过从以下方面生成多层组学数据来支持整个U19提案 作为ADNI、MCSA和5个ADRC的特征良好的队列的一部分收集的生物旋毛虫(Mayo Clinic， 印第安纳大学、佛罗里达大学、密歇根大学和华盛顿大学)。多种生物菌种有 已经或将为每个提案项目收集数据。包括匹配的死后脑组织 和死前血(P1)，或纵向收集的多根血管(P2，P3)，以鉴定分子 与相同个体的丰富表型(病理、成像、临床、生物标志物)数据相关的变化。 将收集代表非西班牙裔白人、拉美裔美国人和非洲裔美国人的不同队列的数据 (nhw、la和aa)种群。建议收集的组学措施包括批量总RNA测序， 来自脑组织和PAX基因血液的单核RNA测序(SnRNASeq)， 脑组织和血浆的蛋白质组，脑组织和血清的代谢组和脂组，DNA 来自脑组织和血液的甲基化以及来自脑组织的基因阵列。这些措施将提供 将在其上检验项目假说的分子图谱。OMICS核心将支持该项目 目标，并通过提供生物样品管理的集中协调来提供协调的组学数据， 创新的研究设计和多组学数据的协调生成。此外，全面的 与生物胺收集、处理和组学数据生成方法相关的文档，这将 为整个U19计划的开放科学目标做出贡献，将提供给行政核心(C1)。 与样品收集、加工、储存和转移有关的批次影响将被考虑并最小化 实现项目和分析核心(C3)的综合分析目标。OMICS核心将解决 通过为以下项目提供集中化研究设计来集成大规模组学数据收集的独特挑战 这些关键程序与每个项目和分析核心进行了磋商。协议已经和 将继续与每个相关参与方的研究协调员协作进行协调 网站。OMICS核心有3个具体目标来满足提案的需求：(1)协调收集， 储存和分发用于组学研究的生物样品；(2)产生协调的高质量组学数据 跨研究地点、组织和队列；(3)提供全面的生物样品和组学文档，以 促进U19项目内部和外部的数据共享。通过这些努力，我们预计将产生 建议的协调组学措施(RNAseq、SnRNAseq、蛋白质组、代谢组、脂组、DNA 甲基化阵列和基因阵列)，并附有适当的详细文件。这些数据将被提供给 U19调查人员和更广泛的研究社区能够集中分析和识别- 相互关联的纵向外周分子签名。

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.