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Metabolomic spectral libraries for data-independent SWATH liquid chromatography mass spectrometry acquisition

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Abstract

High-quality mass spectral libraries have become crucial in mass spectrometry-based metabolomics. Here, we investigate a workflow to generate accurate mass discrete and composite spectral libraries for metabolite identification and for SWATH mass spectrometry data processing. Discrete collision energy (5–100 eV) accurate mass spectra were collected for 532 metabolites from the human metabolome database (HMDB) by flow injection analysis and compiled into composite spectra over a large collision energy range (e.g., 10–70 eV). Full scan response factors were also calculated. Software tools based on accurate mass and predictive fragmentation were specially developed and found to be essential for construction and quality control of the spectral library. First, elemental compositions constrained by the elemental composition of the precursor ion were calculated for all fragments. Secondly, all possible fragments were generated from the compound structure and were filtered based on their elemental compositions. From the discrete spectra, it was possible to analyze the specific fragment form at each collision energy and it was found that a relatively large collision energy range (10–70 eV) gives informative MS/MS spectra for library searches. From the composite spectra, it was possible to characterize specific neutral losses as radical losses using in silico fragmentation. Radical losses (generating radical cations) were found to be more prominent than expected. From 532 metabolites, 489 provided a signal in positive mode [M+H]+ and 483 in negative mode [M-H]−. MS/MS spectra were obtained for 399 compounds in positive mode and for 462 in negative mode; 329 metabolites generated suitable spectra in both modes. Using the spectral library, LC retention time, response factors to analyze data-independent LC-SWATH-MS data allowed the identification of 39 (positive mode) and 72 (negative mode) metabolites in a plasma pool sample (total 92 metabolites) where 81 previously were reported in HMDB to be found in plasma.

Library generation workflow for LC-SWATH MS, using collision energy spread, accurate mass, and fragment annotation.

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Acknowledgements

GH would like to thank SystemsX and the Swiss National Sciences Foundation for the financial support: Projects 51RTP0_151032 and 206021_170779.

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Authors and Affiliations

  1. Life Sciences Mass Spectrometry, Department of Inorganic and Analytical Chemistry, University of Geneva, 24, Quai Ernest Ansermet, 1211, Geneva 4, Switzerland

    Tobias Bruderer, Anita O. Hidasi & Gérard Hopfgartner

  2. School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Rue Michel-Servet 1, 1211, Geneva 4, Switzerland

    Emmanuel Varesio

  3. Sciex, 71 Four Valley Drive, Concord, ON, L4K 4V8, Canada

    Eva Duchoslav & Lyle Burton

  4. Ron Bonner Consulting, Newmarket, ON, L3Y 3C7, Canada

    Ron Bonner

Authors
  1. Tobias Bruderer
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  2. Emmanuel Varesio
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  4. Eva Duchoslav
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Correspondence to Gérard Hopfgartner.

Ethics declarations

Plasma samples were obtained from healthy voluntary who have consented that their donation or some of its components being used for medical research after final anonymization or in a coded form. The plasma samples were provided by the Centre de Transfusion Sanguine, University Hospital Geneva, Geneva, Switzerland. The Human Research Act (HRA) does not apply for the anonymized pooled plasma samples analyzed in the present work (Art. 2 para. 2 let. b and c).

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The authors declare that they have no conflict of interest.

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Bruderer, T., Varesio, E., Hidasi, A.O. et al. Metabolomic spectral libraries for data-independent SWATH liquid chromatography mass spectrometry acquisition. Anal Bioanal Chem 410, 1873–1884 (2018). https://doi.org/10.1007/s00216-018-0860-x

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  • DOI: https://doi.org/10.1007/s00216-018-0860-x

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