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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.

评估跨多个分析平台的蛋白质测量的准确性。我们的NIA资助