A universal language for finding mass spectrometry data patterns

Tito Damiani^#¹, Alan K Jarmusch^#², Allegra T Aron^#³, Daniel Petras^#^{4

5}, Vanessa V Phelan^#⁶, Haoqi Nina Zhao^#⁷, Wout Bittremieux⁷, Deepa D Acharya⁸, Mohammed M A Ahmed^{9

10}, Anelize Bauermeister¹¹, Matthew J Bertin¹², Paul D Boudreau⁹, Ricardo M Borges¹³, Benjamin P Bowen^{14

15}, Christopher J Brown¹⁶, Fernanda O Chagas¹³, Kenneth D Clevenger¹⁷, Mario S P Correia¹⁸, William J Crandall¹⁹, Max Crüsemann^{20

21}, Eoin Fahy²², Oliver Fiehn²³, Neha Garg²⁴, William H Gerwick^{7

25}, Jeffrey R Gilbert¹⁶, Daniel Globisch¹⁸, Paulo Wender P Gomes²⁶, Steffen Heuckeroth²⁷, C Andrew James²⁸, Scott A Jarmusch²⁹, Sarvar A Kakhkhorov³⁰, Kyo Bin Kang³¹, Nikolas Kessler³², Roland D Kersten³³, Hyunwoo Kim³⁴, Riley D Kirk³⁵, Oliver Kohlbacher³⁶, Eftychia E Kontou³⁷, Ken Liu¹⁹, Itzel Lizama-Chamu³⁸, Gordon T Luu³⁸, Tal Luzzatto Knaan³⁹, Helena Mannochio-Russo⁷, Michael T Marty⁴⁰, Yuki Matsuzawa⁴¹, Andrew C McAvoy⁴², Laura-Isobel McCall⁴³, Osama G Mohamed^{44

45}, Omri Nahor³⁹, Heiko Neuweger³², Timo H J Niedermeyer⁴⁶, Kozo Nishida⁴¹, Trent R Northen^{14

15}, Kirsten E Overdahl², Johannes Rainer⁴⁷, Raphael Reher⁴⁸, Elys Rodriguez²³, Timo T Sachsenberg⁴⁹, Laura M Sanchez³⁸, Robin Schmid^{1

7}, Cole Stevens⁵⁰, Shankar Subramaniam²², Zhenyu Tian⁵¹, Ashootosh Tripathi^{33

45}, Hiroshi Tsugawa^{41

52

53}, Justin J J van der Hooft^{54

55}, Andrea Vicini⁴⁷, Axel Walter⁴⁹, Tilmann Weber³⁷, Quanbo Xiong⁵⁶, Tao Xu⁵⁷, Tomáš Pluskal¹, Pieter C Dorrestein⁷, Mingxun Wang⁵⁸

Affiliations

¹ Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague, Czech Republic.
² Metabolomics Core Facility, Immunity, Inflammation, and Disease Laboratory, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
³ Department of Chemistry and Biochemistry, University of Denver, Denver, CO, USA.
⁴ Functional Metabolomics Lab, CMFI Cluster of Excellence, University of Tuebingen, Tuebingen, Germany.
⁵ Department of Biochemistry, University of California Riverside, Riverside, CA, USA.
⁶ Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁷ Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
⁸ Biologicals and Natural Products Discovery, Crop Protection R&D, Corteva Agrisciences, Indianapolis, IN, USA.
⁹ BioMolecular Sciences, School of Pharmacy, University of Mississippi, Oxford, MS, USA.
¹⁰ Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Nasr City, Egypt.
¹¹ Department of Fundamental Chemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil.
¹² Department of Chemistry, Case Western Reserve University, Cleveland, OH, USA.
¹³ Walter Mors Institute of Research on Natural Products, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
¹⁴ Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Lab, Berkeley, CA, USA.
¹⁵ The Joint Genome Institute, Lawrence Berkeley National Lab, Berkeley, CA, USA.
¹⁶ Mass Spectrometry Center of Expertise, Regulatory and Stewardship, Corteva Agrisciences, Indianapolis, IN, USA.
¹⁷ Biologicals and Natural Products, Crop Protection R&D, Corteva Agrisciences, Indianapolis, IN, USA.
¹⁸ Department of Chemistry - BMC, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
¹⁹ Clinical Biomarkers Laboratory, School of Medicine, Emory University, Atlanta, GA, USA.
²⁰ Institute of Pharmaceutical Biology, University of Bonn, Bonn, Germany.
²¹ Institute of Pharmaceutical Biology, Goethe University Frankfurt, Frankfurt, Germany.
²² Department of Bioengineering, University of California San Diego, La Jolla, CA, USA.
²³ West Coast Metabolomics Center, University of California Davis, Davis, CA, USA.
²⁴ School of Chemistry and Biochemistry, Center for Microbial Dynamics and Infection, Georgia Institute of Technology, Atlanta, GA, USA.
²⁵ Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
²⁶ Faculty of Chemistry, Institute of Exact and Natural Science, Federal University of Para, Belem, Brazil.
²⁷ Institute of Inorganic and Analytical Chemistry, University of Münster, Münster, Germany.
²⁸ Center for Urban Waters, University of Washington, Tacoma, WA, USA.
²⁹ Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark.
³⁰ Laboratory of Physical and Chemical Methods of Research, Center for Advanced Technologies, Tashkent, Uzbekistan.
³¹ College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.
³² SW R&D Bioinformatics, Life Science Mass Spectrometry, Bruker Daltonics GmbH & Co. KG, Bremen, Germany.
³³ Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI, USA.
³⁴ College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Goyang, Republic of Korea.
³⁵ College of Pharmacy, University of Rhode Island, Kingston, RI, USA.
³⁶ Applied Bioinformatics, Department of Computer Science, University of Tuebingen, University of Tuebingen; Institute for Bioinformatics and Medical Informatics, University of Tuebingen; Institute for Translational Bioinformatics, University Hospital Tuebingen, Tübingen, Germany.
³⁷ The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby, Denmark.
³⁸ Department of Chemistry and Biochemistry, UC Santa Cruz, Santa Cruz, CA, USA.
³⁹ Department of Marine Biology, The Leon H. Charney School of Marine Sciences, University of Haifa, Haifa, Israel.
⁴⁰ Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, USA.
⁴¹ Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Japan.
⁴² School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, USA.
⁴³ Department of Chemistry and Biochemistry, San Diego State University, San Diego, CA, USA.
⁴⁴ Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
⁴⁵ Natural Products Discovery Core, Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
⁴⁶ Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany.
⁴⁷ Institute for Biomedicine, Eurac Research, Bolzano, Italy.
⁴⁸ Department of Pharmacy, University of Marburg, Marburg, Germany.
⁴⁹ Applied Bioinformatics, Department of Computer Science, University of Tuebingen, University of Tuebingen, Tübingen, Germany.
⁵⁰ Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, Oxford, MS, USA.
⁵¹ Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA.
⁵² RIKEN Center for Integrative Medical Sciences, Tsurumi-ku, Japan.
⁵³ RIKEN Center for Sustainable Resource Science, Tsurumi-ku, Japan.
⁵⁴ Bioinformatics Group, Wageningen University & Research, Wageningen, the Netherlands.
⁵⁵ Department of Biochemistry, University of Johannesburg, Johannesburg, South Africa.
⁵⁶ Crop Protection R&D, Corteva Agrisciences, Indianapolis, IN, USA.
⁵⁷ Data Science and Bioinformatics, Corteva Agrisciences, Dublin, OH, USA.
⁵⁸ Department of Computer Science, University of California Riverside, Riverside, CA, USA. mingxun.wang@cs.ucr.edu.

^# Contributed equally.

PMID: 40355727
PMCID: PMC12334354
DOI: 10.1038/s41592-025-02660-z

A universal language for finding mass spectrometry data patterns

Tito Damiani et al. Nat Methods. 2025 Jun.

. 2025 Jun;22(6):1247-1254.

doi: 10.1038/s41592-025-02660-z. Epub 2025 May 12.

Authors

Affiliations

¹ Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague, Czech Republic.
² Metabolomics Core Facility, Immunity, Inflammation, and Disease Laboratory, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
³ Department of Chemistry and Biochemistry, University of Denver, Denver, CO, USA.
⁴ Functional Metabolomics Lab, CMFI Cluster of Excellence, University of Tuebingen, Tuebingen, Germany.
⁵ Department of Biochemistry, University of California Riverside, Riverside, CA, USA.
⁶ Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁷ Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
⁸ Biologicals and Natural Products Discovery, Crop Protection R&D, Corteva Agrisciences, Indianapolis, IN, USA.
⁹ BioMolecular Sciences, School of Pharmacy, University of Mississippi, Oxford, MS, USA.
¹⁰ Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Nasr City, Egypt.
¹¹ Department of Fundamental Chemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil.
¹² Department of Chemistry, Case Western Reserve University, Cleveland, OH, USA.
¹³ Walter Mors Institute of Research on Natural Products, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
¹⁴ Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Lab, Berkeley, CA, USA.
¹⁵ The Joint Genome Institute, Lawrence Berkeley National Lab, Berkeley, CA, USA.
¹⁶ Mass Spectrometry Center of Expertise, Regulatory and Stewardship, Corteva Agrisciences, Indianapolis, IN, USA.
¹⁷ Biologicals and Natural Products, Crop Protection R&D, Corteva Agrisciences, Indianapolis, IN, USA.
¹⁸ Department of Chemistry - BMC, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
¹⁹ Clinical Biomarkers Laboratory, School of Medicine, Emory University, Atlanta, GA, USA.
²⁰ Institute of Pharmaceutical Biology, University of Bonn, Bonn, Germany.
²¹ Institute of Pharmaceutical Biology, Goethe University Frankfurt, Frankfurt, Germany.
²² Department of Bioengineering, University of California San Diego, La Jolla, CA, USA.
²³ West Coast Metabolomics Center, University of California Davis, Davis, CA, USA.
²⁴ School of Chemistry and Biochemistry, Center for Microbial Dynamics and Infection, Georgia Institute of Technology, Atlanta, GA, USA.
²⁵ Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
²⁶ Faculty of Chemistry, Institute of Exact and Natural Science, Federal University of Para, Belem, Brazil.
²⁷ Institute of Inorganic and Analytical Chemistry, University of Münster, Münster, Germany.
²⁸ Center for Urban Waters, University of Washington, Tacoma, WA, USA.
²⁹ Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark.
³⁰ Laboratory of Physical and Chemical Methods of Research, Center for Advanced Technologies, Tashkent, Uzbekistan.
³¹ College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.
³² SW R&D Bioinformatics, Life Science Mass Spectrometry, Bruker Daltonics GmbH & Co. KG, Bremen, Germany.
³³ Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI, USA.
³⁴ College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Goyang, Republic of Korea.
³⁵ College of Pharmacy, University of Rhode Island, Kingston, RI, USA.
³⁶ Applied Bioinformatics, Department of Computer Science, University of Tuebingen, University of Tuebingen; Institute for Bioinformatics and Medical Informatics, University of Tuebingen; Institute for Translational Bioinformatics, University Hospital Tuebingen, Tübingen, Germany.
³⁷ The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby, Denmark.
³⁸ Department of Chemistry and Biochemistry, UC Santa Cruz, Santa Cruz, CA, USA.
³⁹ Department of Marine Biology, The Leon H. Charney School of Marine Sciences, University of Haifa, Haifa, Israel.
⁴⁰ Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, USA.
⁴¹ Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Japan.
⁴² School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, USA.
⁴³ Department of Chemistry and Biochemistry, San Diego State University, San Diego, CA, USA.
⁴⁴ Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
⁴⁵ Natural Products Discovery Core, Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
⁴⁶ Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany.
⁴⁷ Institute for Biomedicine, Eurac Research, Bolzano, Italy.
⁴⁸ Department of Pharmacy, University of Marburg, Marburg, Germany.
⁴⁹ Applied Bioinformatics, Department of Computer Science, University of Tuebingen, University of Tuebingen, Tübingen, Germany.
⁵⁰ Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, Oxford, MS, USA.
⁵¹ Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA.
⁵² RIKEN Center for Integrative Medical Sciences, Tsurumi-ku, Japan.
⁵³ RIKEN Center for Sustainable Resource Science, Tsurumi-ku, Japan.
⁵⁴ Bioinformatics Group, Wageningen University & Research, Wageningen, the Netherlands.
⁵⁵ Department of Biochemistry, University of Johannesburg, Johannesburg, South Africa.
⁵⁶ Crop Protection R&D, Corteva Agrisciences, Indianapolis, IN, USA.
⁵⁷ Data Science and Bioinformatics, Corteva Agrisciences, Dublin, OH, USA.
⁵⁸ Department of Computer Science, University of California Riverside, Riverside, CA, USA. mingxun.wang@cs.ucr.edu.

^# Contributed equally.

PMID: 40355727
PMCID: PMC12334354
DOI: 10.1038/s41592-025-02660-z

Erratum in

Author Correction: A universal language for finding mass spectrometry data patterns.
Damiani T, Jarmusch AK, Aron AT, Petras D, Phelan VV, Zhao HN, Bittremieux W, Acharya DD, Ahmed MMA, Bauermeister A, Bertin MJ, Boudreau PD, Borges RM, Bowen BP, Brown CJ, Chagas FO, Clevenger KD, Correia MSP, Crandall WJ, Crüsemann M, Fahy E, Fiehn O, Garg N, Gerwick WH, Gilbert JR, Globisch D, Gomes PWP, Heuckeroth S, James CA, Jarmusch SA, Kakhkhorov SA, Kang KB, Kessler N, Kersten RD, Kim H, Kirk RD, Kohlbacher O, Kontou EE, Liu K, Lizama-Chamu I, Luu GT, Luzzatto Knaan T, Mannochio-Russo H, Marty MT, Matsuzawa Y, McAvoy AC, McCall LI, Mohamed OG, Nahor O, Neuweger H, Niedermeyer THJ, Nishida K, Northen TR, Overdahl KE, Rainer J, Reher R, Rodriguez E, Sachsenberg TT, Sanchez LM, Schmid R, Stevens C, Subramaniam S, Tian Z, Tripathi A, Tsugawa H, van der Hooft JJJ, Vicini A, Walter A, Weber T, Xiong Q, Xu T, Pluskal T, Dorrestein PC, Wang M. Damiani T, et al. Nat Methods. 2025 Sep;22(9):1995. doi: 10.1038/s41592-025-02785-1. Nat Methods. 2025. PMID: 40781363 Free PMC article. No abstract available.

Abstract

Despite being information rich, the vast majority of untargeted mass spectrometry data are underutilized; most analytes are not used for downstream interpretation or reanalysis after publication. The inability to dive into these rich raw mass spectrometry datasets is due to the limited flexibility and scalability of existing software tools. Here we introduce a new language, the Mass Spectrometry Query Language (MassQL), and an accompanying software ecosystem that addresses these issues by enabling the community to directly query mass spectrometry data with an expressive set of user-defined mass spectrometry patterns. Illustrated by real-world examples, MassQL provides a data-driven definition of chemical diversity by enabling the reanalysis of all public untargeted metabolomics data, empowering scientists across many disciplines to make new discoveries. MassQL has been widely implemented in multiple open-source and commercial mass spectrometry analysis tools, which enhances the ability, interoperability and reproducibility of mining of mass spectrometry data for the research community.

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Conflict of interest statement

Competing interests: P.C.D. is an advisor to Cybele and a co-founder and scientific advisor to Ometa and Enveda with prior approval by UC San Diego. M.W. is a co-founder of Ometa Labs LLC. R.S., S.H. and T.P. are co-founders of mzio GmbH. T.R.N. is an advisor of Brightseed Bio. J.J.J.v.d.H. is a member of the Scientific Advisory Board of NAICONS Srl., Milano, Italy, and is consulting for Corteva Agriscience, Indianapolis, IN, USA. O.K. and T.S. are officers in OpenMS Inc., a non-profit foundation that manages the international coordination of OpenMS development. The other authors declare no competing interests.

Figures

**Fig. 1. Schematic representation of the MassQL ecosystem.**
a, Examples of molecules that produce distinctive data patterns when measured by MS as mass/charge (*m/z*) and intensity (i) peaks. b, MassQL query representing MS/MS fragmentation patterns that encapsulates a characteristic mass loss. The query can be translated to nine languages for enhanced accessibility. c, MassQL is a universal tool to query MS data. MassQL enables data searching in a single file to entire MS repositories. MassQL has also been incorporated into a wide range of MS software. d, MassQL queries are shared and reused via the Community Compendium, which increases reproducibility and knowledge dissemination.

**Fig. 2. Insights from siderophores at a repository scale.**
a, The MassQL query for iron-binding searches for the characteristic ⁵⁴Fe¹²C peak with 6.3% abundance relative to the ⁵⁶Fe¹²C peak. Peaks queried by MassQL are colored in red. b, The molecular network of MassQL spectra hits after clustering by MSCluster (gray, no MS/MS annotation by GNPS MS/MS library; orange, MS/MS annotation by GNPS MS/MS libraries). Singletons (no neighbors in the network) have been excluded from this molecular network. c, A spectral family of the molecular network containing desferrioxamines, including proton-bound and iron-bound desferrioxamines E, G and B, in addition to structurally related analogs. d, Less than <1% of clustered MS/MS are annotated as siderophores by GNPS libraries when masses associated with ethylenediaminetetraacetic acid (an anticoagulant added to MS samples) are removed from the network.

**Fig. 3. Discovering OPEs at a repository scale.**
a, The general structure of OPEs and the MassQL query for the characteristic phosphate fragment. b, The molecular network of MassQL MS/MS in a repository scale query after clustering by Falcon (green, annotation by GNPS library; blue, annotation by an OPEs list curated by Ye et al.; gray, unannotated). c, Summary of MS matching results (precursor m/z match with 20 ppm mass error) by the GNPS MS/MS library and the OPEs list by Ye et al.. These putative identifications were based on precursor only (level 3 annotations). d, A molecular family shown containing alkyl-OPEs. OPEs reported by Ye et al. or in the MS/MS database search are indicated: tributyl phosphate and dimers (light orange and dark orange), and trioctyl phosphate and dimers (light blue and dark blue). Dibutyl phosphate (green) was not reported by Ye et al. or in the MS/MS database search. The structures displayed are illustrative of one possible isomer of the alkyl chain; the specific structure is beyond the scope of this report.

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References

1. Stein, S. E. & Scott, D. R. Optimization and testing of mass spectral library search algorithms for compound identification. J. Am. Soc. Mass. Spectrom.5, 859–866 (1994). - PubMed
1. Baars, O., Morel, F. M. M. & Perlman, D. H. ChelomEx: isotope-assisted discovery of metal chelates in complex media using high-resolution LC–MS. Anal. Chem.86, 11298–11305 (2014). - PubMed
1. Huber, F. et al. matchms—processing and similarity evaluation of mass spectrometry data. J. Open Source Softw.5, 2411 (2020).
1. Chang, H.-Y. et al. A practical guide to metabolomics software development. Anal. Chem.93, 1912–1923 (2021). - PMC - PubMed
1. Matsuda, F. Regular expressions of MS/MS spectra for partial annotation of metabolite features. Metabolomics12, 113 (2016).

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A universal language for finding mass spectrometry data patterns

Affiliations

A universal language for finding mass spectrometry data patterns

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

Figures

References

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources