Metabolite discovery through global annotation of untargeted metabolomics data.
Li ChenWenyun LuLin WangXi XingZiyang ChenXin TengXianfeng ZengAntonio D MuscarellaYihui ShenAlexis CowanMelanie R McReynoldsBrandon J KennedyAshley M LatoShawn R CampagnaMona SinghJoshua D RabinowitzPublished in: Nature methods (2021)
Liquid chromatography-high-resolution mass spectrometry (LC-MS)-based metabolomics aims to identify and quantify all metabolites, but most LC-MS peaks remain unidentified. Here we present a global network optimization approach, NetID, to annotate untargeted LC-MS metabolomics data. The approach aims to generate, for all experimentally observed ion peaks, annotations that match the measured masses, retention times and (when available) tandem mass spectrometry fragmentation patterns. Peaks are connected based on mass differences reflecting adduction, fragmentation, isotopes, or feasible biochemical transformations. Global optimization generates a single network linking most observed ion peaks, enhances peak assignment accuracy, and produces chemically informative peak-peak relationships, including for peaks lacking tandem mass spectrometry spectra. Applying this approach to yeast and mouse data, we identified five previously unrecognized metabolites (thiamine derivatives and N-glucosyl-taurine). Isotope tracer studies indicate active flux through these metabolites. Thus, NetID applies existing metabolomic knowledge and global optimization to substantially improve annotation coverage and accuracy in untargeted metabolomics datasets, facilitating metabolite discovery.
Keyphrases
- liquid chromatography
- mass spectrometry
- tandem mass spectrometry
- high resolution mass spectrometry
- ultra high performance liquid chromatography
- gas chromatography
- high performance liquid chromatography
- simultaneous determination
- electronic health record
- ms ms
- solid phase extraction
- high resolution
- big data
- rna seq
- small molecule
- healthcare
- gas chromatography mass spectrometry
- data analysis
- deep learning
- computed tomography
- positron emission tomography
- fine needle aspiration
- case control
- magnetic resonance