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.

评估我们 NIA 资助的多个分析平台的蛋白质测量准确性。项目，UH2AG064704“识别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”是一个分阶段的 UH2/UH3 项目，我们目前处于 UH2 阶段。我们实现了具体的里程碑，为 UH3 阶段的开展奠定了基础。 UH2 的主要里程碑，我们正在招募和登记 1,400 名百岁老人及其后代，我们正在收集他们的表型数据、血液和粪便样本在 UH3 阶段，我们将生成多组学。这些样本的概况并将其与人类极端长寿表型相关联。 UH2 阶段的里程碑包括规划组学数据的生成和开发分析我们将在该项目的 UH3 阶段使用的管道我们已经取得了实质性进展。大多数组学数据的注册、数据管理和计划，我们也意识到了以下方面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使用的平台非常协调极端长寿，例如长寿家庭研究和长寿联盟在我们的家长申请中，我们建议使用 SOMAscan 技术来生成血清蛋白质组学。方法包括标记质谱和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方面各有利弊，蛋白质丰度评估的准确性以及蛋白质检测的特异性及其性能尚未实现在这项行政补充请求中，我们建议：生成数据，为选择用于 UH3 阶段的最佳蛋白质组平台提供信息我们有机会与其他人类极限寿命研究合作来比较质量。我们提出了两种使用精心设计的掺入实验的光谱测定法、SOMAscan 和 Olink 平台。具体目标 1：生成 250 个样本的基于 SOMAlogic 的蛋白质组图谱，一个对照条件的一式三份代表，以及 6 个池，其中包括 8 种不同的蛋白质，并以 13 种不同的浓度加标丰度，总共 3 + 3𝑥6𝑥13 = 237 个样本，我们将额外添加 13 个空白样本以确保质量。具体目标 2：对使用该方法生成的蛋白质组图谱进行质量控制分析。 SOMAscan、Olink 和质谱技术将用于分析。基于剂量的蛋白质丰度轨迹，以检测不同池中变化的蛋白质并估计 SOMAscan、Olink 和质谱法蛋白质检测的灵敏度和特异性 Somascan 技术与替代技术生成的数据的比较。将提供关键信息来指导选择用于 UH3 阶段的最佳蛋白质组技术父项目的。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Bayesian differential analysis of cell type proportions: opinion.

细胞类型比例的贝叶斯微分分析：意见。

DOI：
发表时间：
2023
期刊：
影响因子：
0
作者：
Karagiannis, Tanya T;Monti, Stefano;Sebastiani, Paola
通讯作者：
Sebastiani, Paola

Protein cost minimization promotes the emergence of coenzyme redundancy.

蛋白质成本最小化促进了辅酶冗余的出现。

DOI：
发表时间：
2022-04-05
期刊：
影响因子：
11.1
作者：
Goldford, Joshua E;George, Ashish B;Flamholz, Avi I;Segrè, Daniel
通讯作者：
Segrè, Daniel

Multi-Attribute Subset Selection enables prediction of representative phenotypes across microbial populations.

多属性子集选择可以预测微生物种群的代表性表型。

DOI：
发表时间：
2024-04-03
期刊：
影响因子：
5.9
作者：
Herbst, Konrad;Wang, Taiyao;Forchielli, Elena J;Thommes, Meghan;Paschalidis, Ioannis Ch;Segrè, Daniel
通讯作者：
Segrè, Daniel

Bayesian Differential Analysis of Cell Type Proportions.

细胞类型比例的贝叶斯差分分析。