Omics Core

组学核心

• 批准号: 10555725
• 负责人: Mariet Allen
• 金额: $ 406.61万
• 依托单位: MAYO CLINIC JACKSONVILLE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-15 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10555725
• 关键词: Address; African American; Age; American; Autopsy; Biological; Biological Markers; Blood; Brain; Clinic; Clinical; Collaborations; Collecting Tube; Collection; Communication; Communities; Consultations; DNA Methylation; Data; Data Collection; Documentation; Ethnic Origin; Ethnic Population; Generations; Genotype; Goals; Image; Indiana; Individual; Knowledge Portal; Latino; Link; Measures; Metadata; Michigan; Molecular; Molecular Profiling; Multiomic Data; Not Hispanic or Latino; Outcome; Participant; Pathology; Peripheral; Phenotype; Plasma; Population; Population Heterogeneity; Process; Proteome; Protocols documentation; Randomized; Research; Research Design; Research Personnel; Sampling; Serum; Services; Site; Specialist; Testing; Time; Tissues; United States National Institutes of Health; Universities; Washington; Work; brain tissue; cohort; data collection site; data harmonization; data sharing; design; innovation; lipidome; metabolome; multi-ethnic; open data; programs; repository; sample collection; sex; single nucleus RNA-sequencing; transcriptome sequencing

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.

总结 组学核心（核心2）将通过生成多层组学数据来支持整个U19提案， 作为ADNI、MCSA和5种ADRC的良好表征的组群的一部分收集的生物样本（马约诊所， 印第安纳州大学、佛罗里达大学、密歇根大学和华盛顿大学）。多个生物样本 已经或将要为每个提案项目收集。其中包括匹配的死后脑组织 和死前血液（P1），或纵向收集的多个血液管（P2，P3），以鉴定分子 与相同个体的丰富表型（病理学、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色、拉丁裔美国人和非裔美国人的不同队列的数据 (NHW、LA和AA）群体。建议收集的组学测量包括批量总RNA测序， 来自脑组织和PAXgene血液的单核RNA测序（snRNASeq）， 来自脑组织和血浆的蛋白质组，来自脑组织和血清的代谢物组和脂质组，DNA 来自脑组织和血液的甲基化和来自脑组织的基因型阵列。这些措施将提供 用于检验项目假设的分子图谱。Omics核心将支持该项目 目标，并通过提供生物标本管理的集中协调来提供统一的组学数据， 创新的研究设计和多组学数据的协调生成。此外，全面 与生物样本采集、处理和组学数据生成方法相关的文档， 有助于整个U19计划的开放科学目标，将提供给行政核心（C1）。 将考虑并尽量减少与样本采集、处理、储存和转移相关的批次效应 实现项目和分析核心（C3）的综合分析目标。Omics核心将解决 通过提供集中的研究设计来整合大规模组学数据收集的独特挑战， 与每个项目和分析核心协商这些关键过程。协议已经和 将继续与各相关参与方的研究协调员合作， 网站.组学核心有3个具体目标来解决提案的需求：（1）协调收集， 储存和分发用于组学研究的生物标本;（2）生成高质量的组学数据 跨研究中心、组织和队列;（3）提供全面的生物标本和组学文件， 促进U19计划内外的数据共享。通过这些努力，我们期望 提出了协调的组学措施（RNAseq、snRNAseq、蛋白质组、代谢组、脂质组、DNA 甲基化阵列和基因型阵列），并附有适当的详细文件。这些数据将提供给 U19调查人员和更广泛的研究社区，以使分析和识别集中- 连接的纵向外周分子标记。