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Identifying protective omics profiles in centenarians and translating these into preventive and therapeutic strategies

确定百岁老人的保护性组学特征并将其转化为预防和治疗策略

基本信息

批准号：
10449626
负责人：
THOMAS T PERLS
金额：
$ 33.78万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-15 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10449626
关键词：
Administrative Supplement Antibodies Binding Biological Biological Assay Blood Centenarian Charge Collaborations Collection Computing Methodologies Coupled Data Detection Enrollment Family Study Funding Generations Goals Human Infrastructure Label Life Longevity Mainstreaming Mass Spectrum Analysis Measurement Methylation Parents Performance Phase Phenotype Population Preparation Preventive Property Proteins Proteome Proteomics Province Quality Control Reagent Sampling Sensitivity and Specificity Serum Specificity Technology Therapeutic Translating analysis pipeline aptamer base cohort data management design dosage experimental study head-to-head comparison healthy aging metabolomics microbiome research multiple omics next generation sequencing offspring parent grant parent project phenotypic data protein profiling recruit transcriptomics

项目摘要

Assessing accuracy of protein measurements across multiple analytical platforms. Our NIA funded project, UH2AG064704 “Identifying protective omics profiles in centenarians and translating these into preventive and therapeutic strategies”, is a phased UH2/UH3 project. We are currently in the UH2 phase, in which we achieve specific milestones to set the stage for and facilitate the conduct of the UH3 phase. Among the major UH2 milestones, we are recruiting and enrolling 1,400 centenarians and their offspring, and we are collecting their phenotype data, blood and fecal samples. In the UH3 phase, we will generate multi-omics profiles of those samples and correlate them with extreme human longevity phenotypes. Other major milestones of the UH2 phase include planning for the generation of omics data and developing analyses pipelines that we will use in the UH3 phase of the project. We have made substantial progress toward enrollment, data management, and plans for the majority of omics data and we also realized the importance of using an accurate data generating platform that is well harmonized with those used by other studies of human extreme longevity such as the Long Life Family Study and the Longevity Consortium. In our parent application, we proposed to use the SOMAscan technology to generate serum proteomics. Alternative proteomics approaches include labelled mass spectrometry and the Olink Explore platforms. These three mainstream technologies have pros and cons in terms of required sample preparation, coverage of the human proteome, accuracy of protein abundance assessment, and specificity of proteins detection and their performance has not been compared in a comprehensive way. In this request for an administrative supplement we propose to generate data that will inform the choice of the best proteomic platform to be used in the UH3 phase of the project. We have the opportunity to join forces with other studies of human extreme longevity to compare mass spectrometry, SOMAscan and Olink platforms using a well-designed spike-in experiment. We propose two specific aims. Specific Aim 1: To generate SOMAlogic-based proteomic profiles of 250 samples that represent triplicates of one control condition, and 6 pools including 8 different proteins spiked at 13 different abundance, for a total of 3 + 3𝑥6𝑥13 = 237 samples. We will add an additional 13 blank samples for quality control. Specific Aim 2: To conduct quality control analysis of the proteomic profiles generated using the SOMAscan, Olink and Mass-spectrometry technologies. Cleaned and normalized data will be used to analyze the dosage-based trajectories of protein abundance to detect proteins that change in the different pools and to estimate sensitivity and specificity of protein detection of the SOMAscan, Olink and mass-spectrometry technologies. The comparison of data generated with the Somascan technology versus alternative technology will provide critical information to guide the selection of the best proteomic technology to use in the UH3 phase of the parent project.

在多个分析平台上评估蛋白质测量的准确性。我们的NIA资助了项目，UH 2AG 064704“确定百岁老人的保护组学概况，并将其转化为预防和治疗战略”是一个分阶段的UH 2/UH 3项目。我们目前处于UH 2阶段，我们实现了具体的里程碑，为UH 3阶段的进行奠定了基础并促进了该阶段的进行。之间主要的UH 2里程碑，我们正在招募和登记1,400名百岁老人和他们的后代，我们是收集它们的表型数据、血液和粪便样本。在UH 3阶段，我们将生成多组学并将它们与极端的人类长寿表型相关联。其他主要 UH 2阶段的里程碑包括计划生成组学数据和开发分析我们将在项目的UH 3阶段使用的管道。我们已经取得了实质性的进展，注册，数据管理和计划的大部分组学数据，我们也意识到的重要性使用准确的数据生成平台，该平台与其他人类研究所使用的平台协调一致。例如长寿家庭研究和长寿联盟。在我们的父应用程序中，我们建议使用SOMAscan技术来产生血清蛋白质组。替代蛋白质组学这些方法包括标记质谱法和Olink Explore平台。这三个主流技术在所需的样品制备，人类蛋白质组的覆盖范围，蛋白质丰度评估的准确性和蛋白质检测的特异性及其性能还没有进行了全面的比较。在这一行政补充请求中，我们建议生成的数据，将告知选择最好的蛋白质组学平台，用于UH 3阶段的项目我们有机会与其他关于人类极端长寿的研究联合起来，使用精心设计的加标实验，在光谱法、SOMAscan和Olink平台上进行。我们提出了两具体目标。具体目标1：生成250个样本的基于SOMAlogic的蛋白质组学图谱，代表一种对照条件的一式三份，6个样本池包括8种不同的蛋白质，以13种不同的浓度加标丰度，总共3 + 3× 6× 13 = 237个样品。我们将增加额外的13个空白样品的质量控制具体目标2：对使用 SOMAscan、Olink和质谱技术。将使用经过清理和规范化的数据进行分析基于剂量的蛋白质丰度轨迹，以检测不同库中变化的蛋白质，评估SOMAscan、Olink和质谱法蛋白质检测的灵敏度和特异性技术. Somascan技术与替代技术生成的数据比较将提供关键信息，以指导选择最佳蛋白质组学技术用于UH 3阶段的父项目。