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METLIN MS2 molecular standards database: a broad chemical and biological resource

Nature Methods volume 17, pages 953–954 (2020)Cite this article

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To the Editor — Tandem mass spectrometry (MS2) data provide high-confidence molecular identification of known molecules and preliminary characterization of novel, unknown molecules (unknowns). However, for databases to be an effective resource, broad chemical space coverage is necessary. Consequently, we have created METLIN (http://metlin.scripps.edu) a highly annotated and structurally diverse database of over 850,000 molecular standards. METLIN’s tandem mass spectral library numerically covers almost 1% of PubChem’s 93 million compounds, essentially a number that can be characterized as the known chemical space.

The combination of METLIN’s molecular standards and systematically acquired experimental data allows for the examination of the impact that MS2 data has on the identification of known molecules. For example, when METLIN is searched against precursor m/z values at varying parts per million (ppm) errors, the number of hits typically ranges from tens to hundreds of compounds. However, with the addition of MS2 data, the false positive rate can be minimized to only a few compounds. Beyond providing molecular identification through its multiple search capabilities (for example, MS2, batch, name and elemental composition), METLIN’s expansion will facilitate similarity searching. The similarity searching algorithm was originally developed to aid in the identification of unknowns and the discovery of novel molecules4 and operates by using fragment ion data to help align an unknown molecule to compounds with similar fragmentation data within a database to help further identify and characterize it4. METLIN’s fragment ion similarity searching and neutral loss similarity searching are applied in identifying endogenous metabolites, drugs and drug metabolites, as well as biotransformation products of xenobiotics5. METLIN facilitates both endogenous and exogenous compound identification. For example, it contains MS2 data for over 60,000 pyrimidine analogs and over 6,000 purine analogs (Fig. 1b), among others.

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Fig. 1: The METLIN MS2 database.

Data availability

The data in the METLIN database are available at http://metlin.scripps.edu. The data in other databases mentioned in this study were obtained from their websites (accessed in February 2020) or published papers: MoNA (https://mona.fiehnlab.ucdavis.edu/), mzCloud (https://www.mzcloud.org/), GNPS (https://gnps.ucsd.edu/)9, HMDB (https://hmdb.ca/)10 and NIST 17 (https://chemdata.nist.gov/).

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Acknowledgements

This research was partially funded by US National Institutes of Health grants R35 GM130385 (G.S.), P30 MH062261 (G.S.), P01 DA026146 (G.S.) and U01 CA235493 (G.S.) and by Ecosystems and Networks Integrated with Genes and Molecular Assemblies (ENIGMA), a Scientific Focus Area Program at Lawrence Berkeley National Laboratory for the US Department of Energy, Office of Science, Office of Biological and Environmental Research, under contract number DE-AC02-05CH11231 (G.S.).

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  1. These authors contributed equally: Jingchuan Xue, Carlos Guijas.

Authors and Affiliations

  1. Scripps Center for Metabolomics and Mass Spectrometry, Scripps Research Institute, La Jolla, CA, USA

    Jingchuan Xue, Carlos Guijas, H. Paul Benton & Gary Siuzdak

  2. Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Vienna, Austria

    Benedikt Warth

  3. Department of Molecular and Computational Biology, Scripps Research Institute, La Jolla, CA, USA

    Gary Siuzdak

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  1. Jingchuan Xue
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  2. Carlos Guijas
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  3. H. Paul Benton
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Contributions

J.X., C.G., H.P.B., B.W. and G.S. contributed to data collection, analysis, and manuscript writing. J.X. and C.G. share first authorship.

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Correspondence to Gary Siuzdak.

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Editorial note: This article has been peer reviewed.

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Xue, J., Guijas, C., Benton, H.P. et al. METLIN MS2 molecular standards database: a broad chemical and biological resource. Nat Methods 17, 953–954 (2020). https://doi.org/10.1038/s41592-020-0942-5

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