Molecular Profiling (MP) Core G

分子分析 (MP) 核心 G

• 批准号: 10491870
• 负责人: Matt Huentelman
• 金额: $ 294.17万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10491870
• 关键词: Age-associated memory impairment; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Amyloid; Area; B cell repertoire; B-Cell Antigen Receptor; Bar Codes; Biological Assay; Biological Markers; Blood; Blood Cells; Brain; Cognitive; Cognitive aging; Communities; Consultations; Country; DNA; Data; Data Analyses; Data Science Core; Data Set; Deposition; Development; Diabetes Mellitus; Ensure; Epigenetic Process; Genotype; Goals; Hypertension; Immune; Immunologic Markers; Immunologist; Individual; Inflammatory; Lead; Letters; Longevity; Measurement; Measures; Mediating; Molecular; Molecular Analysis; Molecular Profiling; Neurodegenerative Disorders; Participant; Pathway interactions; Peptides; Plasma; Play; Process; RNA; Research; Research Personnel; Resources; Risk Factors; Role; Sampling; Scientist; Ships; Signal Pathway; Sleep; Specimen; Spottings; T-Lymphocyte; Testing; Time; Universities; Viral; Whole Blood; Work; base; biobank; biomarker development; biomarker discovery; blood fractionation; brain pathway; cognitive performance; cohort; data repository; data submission; data warehouse; database of Genotypes and Phenotypes; exosome; experience; genetic risk factor; genome sequencing; genome-wide; genomic data; healthspan; human subject; interest; member; memory consolidation; next generation sequencing; novel; polygenic risk score; protein biomarkers; public database; repository; success; tau Proteins; transcriptome sequencing; whole genome

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).

总结/摘要：分子谱核心G 分子特征分析核心（MP）核心G的目标是（a）履行研究范围内的职责， 生物样本库，包括根据需要跟踪和向项目3及其他核心和项目分发样本， (b)通过NCRAD（国家生物标本集中储存库）促进生物标本的快速公开共享。 阿尔茨海默氏症和相关痴呆症），每年向他们提供两次样本， （c）生成分子数据， 从项目1和2收集的生物标本，（d）提供基因组数据（RNA和 DNA），以确保所有研究数据都是最新的， 他们各自的分析和注释管道，以及（e）提供专家咨询， 生物标志物的发现和发展的精密老化网络（PAN）的研究人员。 项目1生物标本将包括10，000个干血斑卡（DBS）。这些脑深部电刺激样本 从参加MindCrowd扩展的全国分布的个人队列中收集 （MC-扩展）队列。MP Core将对这些标本进行APOE和基于阵列的基因分型， 通过Data Science（DS）Core将原始数据和处理后的数据存款研究数据存储库。这些 项目1的研究人员将利用这些数据来确定与以下疾病相关的遗传风险因素， 在MC-扩展测试组合上的认知表现。此外，通过使用基因组- 广泛的阵列数据，每个参与者将被分配个性化的多基因风险评分（PRS）， 项目2中详述的各种风险因素（例如，阿尔茨海默病、高血压、糖尿病、睡眠等）。 项目2生物标本将包括从面对面采集的1，620份血浆、血清和CSF样本 特征化队列。将从这些样本中生成几个分子分析数据集，包括： 全基因组测序，CSF生物标志物，免疫和炎症测量，泛病毒暴露， T细胞和B细胞受体库、全血和无细胞外泌体RNA测序以及Horvath 表观遗传时钟决定等（在MP核心中进一步详细介绍）。这些数据将是质量 以原始和处理后的格式进行控制并上传至研究数据存储库，供以下人员使用 项目和核心的调查人员。 获得的高质量和广泛的分子数据将在回答重大问题方面发挥重要作用 研究问题，在我们提出的项目，也可以用于国家研究界 研究认知老化、阿尔茨海默氏病（AD）和相关痴呆症（ADRD）。