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 饮食生物标志物发展中心（DBDC）的总体目标是发展目标 可以完成当前饮食摄入量评估方法的饮食摄入的生物标志物。液体 色谱串联质谱 - 基于LC-MS-）分析技术提供了强大的手段 介绍食物生物标志物，包括直接源自食物的营养和非营养分子 它们的代谢产物通过宿主和微生物组通过代谢转化产生。我们建议 在哈佛大学为DBDC创建代谢组学核心，该核心将使用五个免费的套件 在急性喂养研究中发现新食物生物标志物的非靶向LC-MS方法 干预核心并开发针对较大人类人群生物标志物验证研究的有针对性测定法 与生物标志物项目的结合。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广泛研究所的代谢组学平台，并将使用能够高的设备 分辨率和准确的质量（HRAM），用于使用已知身份化合物的杂种分析，证实了使用 参考标准，以及从尚未表征分子的数千个峰。核心将使用 结构阐明工作流程，其中包含专用的Thermo ID-X LC-MS系统，用于广泛 收购产品离子光谱（MS/MS）以及基于机器学习的结构预测 工作流程有效地确定重要未知数的身份。一旦新食物生物标志物已经 鉴定出，核心将使用储存的等离子体和尿 来自人类干预试验的样本（Omniheart的164名参与者）和队列（600名LVS，450名参与者 Solnas）在生物标志物项目中。