Metabolomics Core for the Dietary Biomarkers Development Center at Harvard University

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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.