Biomarker Core

生物标志物核心

• 批准号: 10620824
• 负责人: ANGUS C. NAIRN
• 金额: $ 41.87万
• 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/10620824
• 关键词: Age; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid beta-Protein; Bioinformatics; Biological Assay; Biological Markers; Biological Specimen Banks; Cell Extracts; Clinical; Cognitive; Computational Biology; DNA Integration; 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; biobank; biomarker selection; brain tissue; cell free DNA; data integration; 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BiosPecimen在拟议的Yale ADRC中发挥关键作用 由标准和新型生物测量组成的存储库以及通过开发和应用 尖端的蛋白质组学和表观遗传学测定以及生物信息学方法，以整合高维度 多媒体数据。耶鲁ADRC生物标志物核心管辖权下的方法和生物测量将 促进和验证阿尔茨海默氏病（AD）易感性的有希望的生物标志物， 改善AD风险预测，并确定有望开发目标干预措施的承诺方向。这 生物标志物核心将与管理中的数据管理和统计核心（DMSC）紧密合作 生物测量存储库。我们还将促进多摩斯数据与生成数据的集成 通过临床和成像核心评估和验证标准和新型生物标志物的针对 捕获广告异质性，敏感性和进展。我们将与DMSC合作利用统计信息 认知轨迹和衰落和/或考虑死亡率选择或其他偏见的考虑 评估与广告相关生物标志物的可靠性，有效性和概括性。最后，我们将与 教育部分和外展核心，以促进AD BioMarker获取的培训和外展， 使用。具体目的包括：目标1：管理耶鲁ADRC生物传感存储库。与 临床，神经病理学和DMS核心以及NCRAD，我们将管理耶鲁大学ADRC生物座位和 向ADRC和非ADRC研究人员提供生物测量。目标2：评估，跟踪和验证生物流体和 AD的组织生物标志物。我们将对Abeta1-40，Abeta1-42，T-Tau和P-使用基于ELISA的标准化测定法 Yale Adrc Biorepository的现有和未来生物流体样品中的CSF中的Tau，并利用最先进的 ART针对的质谱分析，以分析来自生物流体和脑组织中选定的生物标志物 Yale ADRC生物座位和其他ADRC附属研究项目。目标3：评估，跟踪和验证 系统级生物标志物基于高维度数据。我们将评估DNA甲基化（DNAM） 来自耶鲁ADRC生物库和其他ADRC附属研究项目的生物流体，并使用它来计算 经过验证和新颖的生物标志物测量表观遗传年龄和AD异质性。与 DMSC，我们将使用系统生物学方法将DNAN和蛋白质组学数据与可用数据集成 通过临床和成像核。目标4：促进AD BioMarker获取的培训和推广， 使用。