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： “多种族人口中的AD（清晰AD）的中央连锁纵向外围生物标志物”是 在13个机构中，来自多个学科的40位专家的协作U19申请了8个机构 来自> 3,700个人的独立NIH资助的人群> 7,000个大脑和> 13,000个血液样本 > 20,000个多摩斯数据点将与> 48,000个协调的阿尔茨海默氏病产生并集成 （AD）在此U19下的内表型。我们的目标是发现，复制和验证广告的下一代 血液多矩生物标志物候选者，代表大脑中分子扰动特征 反映在抗降量神经影像学/脑脊液（CSF）和验尸后神经病理学表型中 这种复杂的疾病。我们的目的是发现可以发现的中心连接的外围分子特征（CLPMS） 通过转录组，表观基因组，蛋白质组，充当未来的中心链接外围生物标志物（CLPBM） 代谢组/脂多组数据生成，与现有其他摩体数据的集成以及匹配中的分析 尸体后大脑：反典礼血液样本（项目1 = P1）;并表征他们的纵向动态 非裔美国人的非西班牙裔白人（NHW）和潜水员的个人资料 （AA）和拉丁裔美国人（LA）参与者（P2，P3）。我们期望确定预测性，诊断性，预后和 具有机械见解的治疗性AD生物标志物；为了增强反复试验的多种族的生物标志物研究 人口并为研究社区提供大量严格生成，复制和 经过验证的多派生物标志物。为了实现这些目标，我们将利用并整合现有和将来的数据 以及来自阿尔茨海默氏病神经影像学计划（ADNI），梅奥诊所衰老研究（MCSA）的生物测量（ADNI） 和6个广告研究中心（ADRC）。行政核心（核心1：C1）将提供指导和监督 到该计划的项目和核心（C2。Omics和C3。AnalyticCores），并促进其执行。这 行政核心将通过1）集成参与机构以及 研究； 2）执行所有监管活动； 3）为来自学员的多元学者计划 urps; 4）在U19内实现沟通，外展和知识共享，与相关计划， 整个研究社区和公共利益相关者； 5）确保严格，可重复性和透明度 制作研究界所有数据，算法和结果。具体目标 行政核心是：1）提供指导，监督，集成和促进所有U19的执行 在其指导委员会，外部顾问委员会和NIH（1A）的领导下的目标；并执行全部 该计划的监管活动（1B）。 2）通过建立U19进行外展和教育 多样性学者计划培训AA和LA科学家（2A）和两年一次的会议（2B）。 3）共享数据 和知识以NIH认可的存储库以促进透明度的开放态度， 可重复性和所有Clear-AD计划资产的重复使用。