In silico fragmentation for computer assisted identification of metabolite mass spectra
Open accessAbstract
BACKGROUND: Mass spectrometry has become the analytical method of choice in metabolomics research. The identification of unknown compounds is the main bottleneck. In addition to the precursor mass, tandem MS spectra carry informative fragment peaks, but the coverage of spectral libraries of measured reference compounds are far from covering the complete chemical space. Compound libraries such as PubChem or KEGG describe a larger number of compounds, which can be used to compare their in silico fragmentation with spectra of unknown metabolites. RESULTS: We created the MetFrag suite to obtain a candidate list from compound libraries based on the precursor mass, subsequently ranked by the agreement between measured and in silico fragments. In the evaluation MetFrag was able to rank most of the correct compounds within the top 3 candidates returned by an exact mass query in KEGG. Compared to a previously published study, MetFrag obtained better results than the commercial MassFrontier software. Especially for large compound libraries, the candidates with a good score show a high structural similarity or just different stereochemistry, a subsequent clustering based on chemical distances reduces this redundancy. The in silico fragmentation requires less than a second to process a molecule, and MetFrag performs a search in KEGG or PubChem on average within 30 to 300 seconds, respectively, on an average desktop PC. CONCLUSIONS: We presented a method that is able to identify small molecules from tandem MS measurements, even without spectral reference data or a large set of fragmentation rules. With today's massive general purpose compound libraries we obtain dozens of very similar candidates, which still allows a confident estimate of the correct compound class. Our tool MetFrag improves the identification of unknown substances from tandem MS spectra and delivers better results than comparable commercial software. MetFrag is available through a web application, web services and as java library. The web frontend allows the end-user to analyse single spectra and browse the results, whereas the web service and console application are aimed to perform batch searches and evaluation.
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Software tools such as MetFrag, MyCompoundID, MetiTree, and Mass Frontier can handle metabolite fragmentation data and permit library searches for candidates using in silico fragmentation predictions or comparisons to previously fragmented metabolites or standards.
“Software tools such as MetFrag, MyCompoundID, MetiTree, and Mass Frontier can handle metabolite fragmentation data and permit library searches for potential candidates using in silico fragmentation predictions of metabolites or comparisons to previously fragmented metabolites or standards (146, 153-155).”
From The food metabolome: a window over dietary exposure (2014) · cites this paper as [153]
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- Authors
- Wolf, S., Schmidt, S., Müller-Hannemann, M., & Neumann, S.
- Affiliations
- Leibniz Institute of Plant Biochemistry (DE)
- Corresponding author
- Wolf, Sebastian
- ORCID
- Neumann, Steffen
- Venue
- BMC Bioinformatics
- Published
- 2010-03-22
- Volume
- 11
- Issue
- 1
- Pages
- 148-148
- ISSN
- 1471-2105 (ISSN-L)
- PMC
- PMC2853470
- OpenAlex
- W2015503332
- Cited by
- 698
- References
- 19
- Citations by year
- 2026: 19 · 2025: 37 · 2024: 42 · 2023: 43 · 2022: 35 · 2021: 53 · 2020: 52 · 2019: 56 · 2018: 51 · 2017: 47 · 2016: 57 · 2015: 63 · 2014: 54 · 2013: 43 · 2012: 24
- FWCI
- 11.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Bioinformatics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- in silico fragmentation, tandem mass spectrometry, metabolite identification, MetFrag, chemical libraries, KEGG, PubChem, spectral library search, candidate ranking, stereochemistry, web application
- MeSH terms
- Mass Spectrometry, Databases, Factual, Proteomics, Metabolomics
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