Metabolomics Core for the Dietary Biomarkers Development Center at Harvard University

哈佛大学膳食生物标志物开发中心的代谢组学核心

• 批准号: 10649590
• 负责人: Clary B Clish
• 金额: $ 25.1万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-16 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10649590
• 关键词: Acute; Address; Algorithms; Award; Biological; Biological Assay; Biological Markers; Biomarker of Dietary Intake; Charge; Collaborations; Complement; Contracts; Coupled; Data; Data Analyses; Dedications; Dietary intake; Equipment; Food; Goals; Human; Human Microbiome; Hybrids; Intervention; Intervention Trial; Ions; Libraries; Lipids; Liquid Chromatography; Machine Learning; Measurement; Measures; Metabolic; Methods; Molecular; Nutrient; Participant; Physical activity; Plasma; Procedures; Protocols documentation; Reference Standards; Resolution; Resources; Sampling; Specimen; Structure; System; Technology; Trans-Omics for Precision Medicine; Transducers; U-Series Cooperative Agreements; United States National Institutes of Health; Universities; Urine; Validation; biomarker development; biomarker discovery; biomarker validation; chemical property; cohort; data sharing; design; dietary; experience; feeding; instrumentation; metabolomics; metabolomics resource; microbiome; novel; physical property; programs; tandem mass spectrometry; targeted biomarker; validation studies

PROJECT SUMMARY – METABOLOMICS CORE The overarching goal of the Dietary Biomarker Development Centers (DBDCs) is to develop objective biomarkers of dietary intake that can complement current dietary intake assessment methods. Liquid chromatography tandem mass spectrometry- (LC-MS-) based profiling technologies provide a powerful means to profile food biomarkers, including nutrient and non-nutrient molecules directly derived from food as well as their metabolites generated via metabolic transformation by both the host and the microbiome. We propose creating a Metabolomics Core for the DBDC at Harvard University that will use a suite of five complimentary nontargeted LC-MS methods to discover new food biomarkers in acute feeding studies conducted by the Intervention Core and to develop targeted assays for biomarker validation studies in larger human cohorts in conjunction with the Biomarkers Project. The Core will leverage existing expertise and resources of the Metabolomics Platform at the Broad Institute of MIT and Harvard and will use equipment capable of high resolution and accurate mass (HRAM) for hybrid analyses of compounds of known identity, confirmed using reference standards, and thousands of peaks from yet to be characterized molecules. The Core will use a structure elucidation workflow that incorporates a dedicated Thermo ID-X LC-MS system for extensive acquisition of product ion spectra (MS/MS) coupled with a machine learning-based structure prediction workflow to efficiently determine identities of important unknowns. Once new food biomarkers have been identified, the Core will develop targeted triple quadrupole MS-based assays using stored plasma and urine samples from a human intervention trial (164 participants in OmniHeart) and cohorts (600 in LVS and 450 in SOLNAS) in the Biomarkers Project.

项目摘要——代谢组学核心 膳食生物标志物开发中心 (DBDC) 的总体目标是制定目标 膳食摄入的生物标志物可以补充当前的膳食摄入液体评估方法。 基于色谱串联质谱 (LC-MS) 的分析技术提供了强大的手段 分析食品生物标志物，包括直接源自食品以及食品的营养分子和非营养分子 我们建议，它们的代谢物是通过宿主和微生物组的代谢转化而产生的。 为哈佛大学的 DBDC 创建代谢组学核心，该核心将使用一套五个免费的 非靶向 LC-MS 方法在急性喂养研究中发现新的食品生物标志物 干预核心并开发针对更大人类队列的生物标志物验证研究的靶向测定法 与生物标记项目相结合，核心将利用现有的专业知识和资源。 麻省理工学院和哈佛大学博德研究所的代谢组学平台将使用具有高通量能力的设备 分辨率和精确质量 (HRAM)，用于对已知身份的化合物进行混合分析，并使用 参考标准，以及来自尚未表征的分子的数千个峰，Core 将使用 结构解析工作流程，包含专用的 Thermo ID-X LC-MS 系统，可用于广泛的分析 采集产物离子谱 (MS/MS) 并结合基于机器学习的结构预测 一旦新的食品生物标志物出现，就可以有效地确定重要未知物的身份。 确定后，Core 将使用储存的血浆和尿液开发基于三重四极杆 MS 的靶向检测 来自人类干预试验（OmniHeart 的 164 名参与者）和队列（LVS 中的 600 名参与者和 LVS 中的 450 名参与者）的样本 SOLNAS）在生物标志物项目中。