期刊
METABOLOMICS
卷 15, 期 7, 页码 -出版社
SPRINGER
DOI: 10.1007/s11306-019-1564-8
关键词
Targeted metabolomics; LC-MS; MS; RPLC; HILIC; Measurement reliability; Amino acids; Metabolite dynamics
资金
- University of Michigan's Program in Chemical Biology Graduate Assistance in Areas of National Need (GAANN) award
- Pancreatic Cancer Action Network/AACR Pathway to Leadership award [13-70-25-LYSS]
- Dale F. Frey Award for Breakthrough Scientists from the Damon Runyon Cancer Research Foundation [DFS-09-14]
- Junior Scholar Award from The V Foundation for Cancer Research [V2016-009]
- Kimmel Scholar Award from the Sidney Kimmel Foundation for Cancer Research [SKF-16-005]
- 2017 AACR NextGen Grant for Transformative Cancer Research [17-20-01-LYSS]
- UMCCC Core Grant [P30 CA046592]
- NIH [DK097153]
- Charles Woodson Research Fund
- UM Pediatric Brain Tumor Initiative
IntroductionWe previously developed a tandem mass spectrometry-based label-free targeted metabolomics analysis framework coupled to two distinct chromatographic methods, reversed-phase liquid chromatography (RPLC) and hydrophilic interaction liquid chromatography (HILIC), with dynamic multiple reaction monitoring (dMRM) for simultaneous detection of over 200 metabolites to study core metabolic pathways.ObjectivesWe aim to analyze a large-scale heterogeneous data compendium generated from our LC-MS/MS platform with both RPLC and HILIC methods to systematically assess measurement quality in biological replicate groups and to investigate metabolite abundance changes and patterns across different biological conditions.MethodsOur metabolomics framework was applied in a wide range of experimental systems including cancer cell lines, tumors, extracellular media, primary cells, immune cells, organoids, organs (e.g. pancreata), tissues, and sera from human and mice. We also developed computational and statistical analysis pipelines, which include hierarchical clustering, replicate-group CV analysis, correlation analysis, and case-control paired analysis.ResultsWe generated a compendium of 42 heterogeneous deidentified datasets with 635 samples using both RPLC and HILIC methods. There exist metabolite signatures that correspond to various phenotypes of the heterogeneous datasets, involved in several metabolic pathways. The RPLC method shows overall better reproducibility than the HILIC method for most metabolites including polar amino acids. Correlation analysis reveals high confidence metabolites irrespective of experimental systems such as methionine, phenylalanine, and taurine. We also identify homocystine, reduced glutathione, and phosphoenolpyruvic acid as highly dynamic metabolites across all case-control paired samples.ConclusionsOur study is expected to serve as a resource and a reference point for a systematic analysis of label-free LC-MS/MS targeted metabolomics data in both RPLC and HILIC methods with dMRM.
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