Administrative Core

行政核心

• 批准号: 10555724
• 负责人: NILUFER ERTEKIN-TANER
• 金额: $ 52.77万
• 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/10555724
• 关键词: Acceleration; Accountability; African American; African American population; Aging; Agreement; Algorithms; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease therapeutic; Alzheimer’s disease biomarker; American; Autopsy; Biological Markers; Blood; Blood Vessels; Blood specimen; Brain; Cell Nucleus; Cerebrospinal Fluid; Clinic; Collaborations; Communication; Communities; Complex; DNA Methylation; Data; Data Set; Dementia; Diagnostic; Discipline; Disease; Education and Outreach; Ensure; Ethnic Population; Etiology; Feedback; Funding; Future; Generations; Goals; Hematological Disease; Indiana; Individual; Institution; Institutional Review Boards; Knowledge; Knowledge Portal; Latino; Leadership; Link; Medicine; Michigan; Molecular; Molecular Profiling; Multiomic Data; Not Hispanic or Latino; Outcome; Participant; Peripheral; Phenotype; Proteome; Reproducibility; Research; Research Personnel; Resources; Sampling; Scholars Program; Scientist; Training; Training Programs; Underrepresented Populations; United States National Institutes of Health; Universities; Washington; Work; candidate marker; career; cohort; data integration; data sharing; endophenotype; epigenome; insight; lipidome; material transfer agreement; meetings; metabolome; multi-ethnic; multiple omics; neuroimaging; neuropathology; next generation; open data; outreach; prognostic; programs; repository; resilience; success; symposium; transcriptome; transcriptome sequencing; trial readiness; working group

Summary Abstract: “Centrally-linked Longitudinal pEripheral biomARkers of AD (CLEAR-AD) in multi-ethnic populations” is a collaborative U19 application of >40 experts from multiple disciplines, across 13 institutions leveraging 8 independent NIH-funded cohorts of >7,000 brain and >13,000 blood samples from >3,700 individuals, in which >20,000 multi-omics data points will be generated and integrated with >48,000 harmonized Alzheimer’s disease (AD) endophenotypes under this U19. Our goal is to discover, replicate and validate the next-generation of AD blood multi-omics biomarker candidates that represent molecular perturbation signatures in the brain which are reflected in antemortem neuroimaging/cerebrospinal fluid (CSF) and post-mortem neuropathology phenotypes of this complex disease. We aim to discover centrally-linked peripheral molecular signatures (CLPMS) that can serve as future centrally-linked peripheral biomarkers (CLPBM) through transcriptome, epigenome, proteome, metabolome/lipidome data generation, integration with existing other -omics data and analysis in matched postmortem brain:antemortem blood samples (Project 1=P1); and to characterize their longitudinal dynamic profiles in non-Hispanic white (NHW) and diverse, underrepresented populations (URP) of African American (AA) and Latino American (LA) participants (P2, P3). We expect to identify predictive, diagnostic, prognostic and therapeutic AD biomarkers with mechanistic insights; to enhance biomarker research in trial-ready multi-ethnic populations and to provide the research community with a vast resource of rigorously generated, replicated and validated multi-omics biomarkers. To achieve these aims, we will utilize and integrate existing and future data and biospecimens from Alzheimer’s Disease Neuroimaging Initiative (ADNI), Mayo Clinic Study of Aging (MCSA) and 6 AD Research Centers (ADRCs). The Administrative Core (Core 1: C1) will provide direction and oversight to the projects and cores of this program (C2. Omics and C3. Analytic Cores) and facilitate their execution. The Administrative Core will achieve the program goals through 1) integration of the participating institutions and studies; 2) execution of all regulatory activities; 3) establishing a Diversity Scholars Program for trainees from URPs; 4) enabling communication, outreach and knowledge sharing within the U19, with related programs, the whole research community and public stakeholders; and 5) ensuring rigor, reproducibility and transparency by making all data, algorithms, and outcomes available to the research community. The Specific Aims for the Administrative Core are: 1) To provide direction, oversight, integration and facilitate execution of all U19 aims under the leadership of its Steering Committee, External Advisory Board and NIH (1a); and to execute all regulatory activities for the program (1b). 2) To perform outreach and education by establishing a U19 Diversity Scholars Program to train AA and LA scientists (2a) and bi-annual meetings (2b). 3) To share data and knowledge in an open-science fashion on NIH approved repositories to promote transparency, reproducibility and reuse of all CLEAR-AD program assets.

摘要摘要： 《多民族人群阿尔茨海默病的中央连锁纵向外周生物标志物(Clear-AD)》是一个 来自多个学科的40名专家的U19协作应用，跨越13个机构，利用8 由美国国立卫生研究院资助的独立队列，包括来自3,700人的7,000个大脑样本和13,000个血液样本，其中 将生成20,000个多组学数据点，并将其与48,000个协调的阿尔茨海默病进行集成 (Ad)本U19规定的内表型。我们的目标是发现、复制和验证新一代AD 血液多组学生物标记物候选代表大脑中的分子扰动信号 反映在生前神经影像/脑脊液和死后神经病理表型 这种复杂的疾病。我们的目标是发现中心连接的外周分子签名(CLPM)，它可以 通过转录组、表观基因组、蛋白质组、 代谢组/脂组数据的生成、与现有其他组学数据的集成和配对中的分析 死后脑：死前血液样本(项目1=P1)；并描述其纵向动态 非西班牙裔白人(NHW)和多元化、代表性不足的非裔美国人(URP)的概况 (AA)和拉美裔(LA)参与者(P2、P3)。我们希望确定预测性、诊断性、预期性和 具有机械洞察力的治疗性AD生物标记物；在准备进行试验的多种族中加强生物标记物研究 并向研究界提供大量严格生成、复制和 经过验证的多组学生物标志物。为了实现这些目标，我们将利用和整合现有和未来的数据 和来自阿尔茨海默病神经成像倡议(ADNI)、梅奥衰老临床研究(MCSA)的生物样本 和6个AD研究中心(ADRC)。行政核心(核心1：C1)将提供指导和监督 本计划的项目和核心(C2.组学和C3。分析核心)，并促进它们的执行。这个 管理核心将通过1)整合参与机构和 研究；2)执行所有监管活动；3)为来自以下国家的受训者建立多样化学者方案 URP；4)通过相关方案，促进U19内部的沟通、外联和知识共享 整个研究界和公众利益攸关方；以及5)通过以下方式确保严谨性、可重复性和透明度 将所有数据、算法和结果提供给研究社区。该计划的具体目标 行政核心是：1)提供指导、监督、整合和促进所有U19的执行 在其指导委员会、外部咨询委员会和国家卫生研究院(1a)的领导下制定目标；并执行所有 该计划的监管活动(1b)。2)通过建立U19进行外展和教育 多样性学者方案，培训AA和LA科学家(2a)和两年一次的会议(2b)。3)共享数据 以及在NIH批准的知识库上以开放科学的方式提供知识，以促进透明度， 所有Clear-AD计划资产的再现性和可重用性。