Enhancing tandem mass spectrometry-based metabolite annotation with online chemical labeling

  • Nat Commun. 2025 Jul 26;16(1):6911. doi: 10.1038/s41467-025-61240-z.
Giovanni Andrea Vitale  #  1 ,  Shu-Ning Xia  #  1 ,  Kai Dührkop  2  3 ,  Mohammad Reza Zare Shahneh  4 ,  Heike Brötz-Oesterhelt  1  5  6 ,  Yvonne Mast  7 ,  Corinna Brungs  8  9 ,  Sebastian Böcker  2 ,  Robin Schmid  8  10 ,  Mingxun Wang  4 ,  Chambers C Hughes  11  12  13 ,  Daniel Petras  14  15
Affiliations
  • 1. Department of Microbial Bioactive Compounds, Interfaculty Institute of Microbiology and Infection Medicine (IMIT), University of Tübingen, Tübingen, Germany.
  • 2. Chair for Bioinformatics, Institute for Computer Science, Friedrich Schiller University Jena, Jena, Germany.
  • 3. Bright Giant GmbH, Jena, Germany.
  • 4. Department of Computer Science, University of California Riverside, Riverside, CA, USA.
  • 5. German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany.
  • 6. Cluster of Excellence EXC 2124: Controlling Microbes to Fight Infection, University of Tübingen, Tübingen, Germany.
  • 7. Department Bioresources for Bioeconomy and Health Research, Leibniz Institute DSMZ - German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany.
  • 8. Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague, Czech Republic.
  • 9. Division of Pharmacognosy, Department of Pharmaceutical Sciences, Faculty of Life Sciences, University of Vienna, Vienna, Austria.
  • 10. mzio GmbH, Bremen, Germany.
  • 11. Department of Microbial Bioactive Compounds, Interfaculty Institute of Microbiology and Infection Medicine (IMIT), University of Tübingen, Tübingen, Germany. [email protected].
  • 12. German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany. [email protected].
  • 13. Cluster of Excellence EXC 2124: Controlling Microbes to Fight Infection, University of Tübingen, Tübingen, Germany. [email protected].
  • 14. Cluster of Excellence EXC 2124: Controlling Microbes to Fight Infection, University of Tübingen, Tübingen, Germany. [email protected].
  • 15. Department of Biochemistry, University of California Riverside, Riverside, CA, USA. [email protected].
  • # Contributed equally.
PMID: 40715063 DOI: 10.1038/s41467-025-61240-z
Abstract

Metabolite identification in non-targeted mass spectrometry-based metabolomics remains a major challenge due to limited spectral library coverage and difficulties in predicting metabolite fragmentation patterns. Here, we introduce Multiplexed Chemical Metabolomics (MCheM), which employs orthogonal post-column derivatization reactions integrated into a unified mass spectrometry data framework. MCheM generates orthogonal structural information that substantially improves metabolite annotation through in silico spectrum matching and open-modification searches, offering a powerful new toolbox for the structure elucidation of unknown metabolites at scale.

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