Biomarker Core

生物标志物核心

• 批准号: 10180855
• 负责人: ANGUS C. NAIRN
• 金额: $ 41.88万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-15 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10180855
• 关键词: Age; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Bioinformatics; Biological Assay; Biological Markers; Biological Specimen Banks; Cell Extracts; Clinical; Cognitive; Computational Biology; DNA Methylation; Data; Databases; Development; Disease susceptibility; Education; Education and Outreach; Enzyme-Linked Immunosorbent Assay; Epigenetic Process; Future; Gene Expression; Genetic; Health and Retirement Study; Human; Image; Immune; Intervention; Knowledge Portal; Mass Spectrum Analysis; Measures; Methodology; Methods; Modeling; Molecular; Multiomic Data; NIH Program Announcements; Pathway Analysis; Play; Predisposition; Protein Analysis; Proteomics; Research; Research Personnel; Research Project Grants; Sampling; Scientist; Standardization; Statistical Models; System; Systems Biology; Tissue Banks; Training; Validation; Validity and Reliability; Work; assay development; base; biobank; brain tissue; cell free DNA; data management; design; disease heterogeneity; experience; high dimensionality; improved; member; mortality; neuropathology; novel; novel marker; outreach; protein biomarkers; risk prediction; statistics; tau Proteins; tau-1; tissue biomarkers; transcriptomics

The Biomarker Core will play a key role in the proposed Yale ADRC by managing the Biospecimen Repository consisting of both standard and novel biospecimens, and through the development and application of cutting-edge proteomic and epigenetic assays and bioinformatics approaches to integrate high-dimensional multi-omics data. Methods and biospecimens under the jurisdiction of the Yale ADRC Biomarker Core will facilitate the development and validation of promising biomarkers of Alzheimer’s disease (AD) susceptibility, improve AD risk prediction, and identify promising directions for development of targeted interventions. The Biomarker Core will work closely with the Data Management and Statistics Core (DMSC) in the management of the Biospecimens Repository. We will also facilitate the integration of multi-omics data with data generated by the Clinical and Imaging Cores to assess and validate both standard and novel biomarkers aimed at capturing AD heterogeneity, susceptibility, and progression. We will work with the DMSC to utilize statistical modeling of cognitive trajectories and decline, and/or considerations of mortality selection or other biases when evaluating the reliability, validity, and generalizability of AD-related biomarkers. Finally, we will work with the Education Component and Outreach Core to facilitate training and outreach in AD Biomarker acquisition and use. Specific Aims include: Aim 1: Manage Yale ADRC Biospecimen Repository. Working closely with the Clinical, Neuropathology, and DMS Cores, and NCRAD, we will manage the Yale ADRC biorepository and provide biospecimens to ADRC and non-ADRC investigators. Aim 2: Assess, track and validate biofluid and tissue biomarkers of AD. We will use standardized ELISA-based assays for Abeta1-40, Abeta1-42, t-tau and p- tau in CSF in existing and future biofluid samples from Yale ADRC Biorepository, as well as utilize state-of-the- art targeted mass spectrometric assays to analyze selected biomarkers in biofluid and brain tissue from the Yale ADRC Biorepository and other ADRC-affiliated research projects. Aim 3: Assess, track and validate systems-level biomarkers based on high-dimensional omics data. We will assess DNA methylation (DNAm) in biofluids from the Yale ADRC Biorepository and other ADRC-affiliated research projects, and use it to calculate both validated and novel biomarker measures of epigenetic age and AD heterogeneity. Working with the DMSC, we will use systems biology approaches to integrate the DNAm and proteomic data with data available via the Clinical and Imaging Cores. Aim 4: Facilitate training and Outreach in AD Biomarker acquisition and use.

生物标志物核心将通过管理生物样本在拟议的耶鲁ADRC中发挥关键作用 包括标准和新型生物标本的储存库，并通过开发和应用 尖端的蛋白质组学和表观遗传学分析以及生物信息学方法， 多组学数据。耶鲁ADRC生物标志物核心管辖范围内的方法和生物标本将 促进阿尔茨海默病（AD）易感性的有前景的生物标志物的开发和验证， 改善AD风险预测，并为有针对性的干预措施的发展确定有希望的方向。的 生物标志物核心将与数据管理和统计核心（DMSC）在管理方面密切合作 生物标本储藏室我们还将促进多组学数据与生成的数据的集成 由临床和成像核心评估和验证标准和新型生物标志物， 捕获AD异质性、易感性和进展。我们将与DMSC合作， 认知轨迹和衰退的建模，和/或死亡率选择或其他偏见的考虑， 评估AD相关生物标志物的可靠性、有效性和普遍性。最后，我们将与 教育部分和推广核心，以促进AD生物标志物获取方面的培训和推广， 使用.具体目标包括：目标1：管理耶鲁ADRC生物标本库。密切配合 临床、神经病理学、DMS核心和NCRAD，我们将管理耶鲁ADRC生物储存库， 向ADRC和非ADRC研究者提供生物标本。目标2：评估、跟踪和验证生物流体， AD的组织生物标志物。我们将使用标准化的基于ELISA的检测方法检测A β 1 -40、A β 1 -42、t-tau和p- 来自耶鲁ADRC生物储存库的现有和未来生物流体样本中CSF中的tau蛋白，以及利用 ART靶向质谱测定，以分析来自脑组织的生物流体和脑组织中的选定生物标志物。 Yale ADRC Biorepository和其他ADRC附属研究项目。目标3：评估、跟踪和验证 基于高维组学数据的系统级生物标志物。我们将评估DNA甲基化（DNAm）， 来自耶鲁ADRC生物储存库和其他ADRC附属研究项目的生物流体，并使用它来计算 表观遗传年龄和AD异质性的经验证的和新的生物标志物测量。会同 DMSC，我们将使用系统生物学的方法来整合DNAm和蛋白质组学数据与现有数据 通过临床和成像核心。目标4：促进AD生物标志物获取方面的培训和推广， 使用.