2. Academic Validation
  3. Enhancing tandem mass spectrometry-based metabolite annotation with online chemical labeling

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

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. chambers.hughes@uni-tuebingen.de.
  • 12 German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany. chambers.hughes@uni-tuebingen.de.
  • 13 Cluster of Excellence EXC 2124: Controlling Microbes to Fight Infection, University of Tübingen, Tübingen, Germany. chambers.hughes@uni-tuebingen.de.
  • 14 Cluster of Excellence EXC 2124: Controlling Microbes to Fight Infection, University of Tübingen, Tübingen, Germany. functionalmetabolomics@gmail.com.
  • 15 Department of Biochemistry, University of California Riverside, Riverside, CA, USA. functionalmetabolomics@gmail.com.
  • # 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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