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Combining mass spectrometry and machine learning to discover bioactive peptides

Author

Listed:
  • Christian T. Madsen

    (Global Research Technologies, Novo Nordisk A/S)

  • Jan C. Refsgaard

    (Global Research Technologies, Novo Nordisk A/S
    Intomics)

  • Felix G. Teufel

    (Global Research Technologies, Novo Nordisk A/S)

  • Sonny K. Kjærulff

    (Global Research Technologies, Novo Nordisk A/S
    Intomics)

  • Zhe Wang

    (Novo Nordisk Research Centre China)

  • Guangjun Meng

    (Novo Nordisk Research Centre China
    Pulmongene LTD. Rm 502)

  • Carsten Jessen

    (Global Research Technologies, Novo Nordisk A/S)

  • Petteri Heljo

    (Global Research Technologies, Novo Nordisk A/S)

  • Qunfeng Jiang

    (Novo Nordisk Research Centre China
    Innovent Biologics, Inc. DongPing Jie 168)

  • Xin Zhao

    (Novo Nordisk Research Centre China)

  • Bo Wu

    (Novo Nordisk Research Centre China
    QL Biopharmaceutical, Rm 101)

  • Xueping Zhou

    (Novo Nordisk Research Centre China
    Crinetics pharmaceuticals)

  • Yang Tang

    (Novo Nordisk Research Centre China
    Roche R&D Center (China) Ltd)

  • Jacob F. Jeppesen

    (Global Research Technologies, Novo Nordisk A/S)

  • Christian D. Kelstrup

    (Global Research Technologies, Novo Nordisk A/S)

  • Stephen T. Buckley

    (Global Research Technologies, Novo Nordisk A/S)

  • Søren Tullin

    (Global Research Technologies, Novo Nordisk A/S
    Boehringer Ingelheim GmbH & Co. KG)

  • Jan Nygaard-Jensen

    (Global Research Technologies, Novo Nordisk A/S
    Boehringer Ingelheim GmbH & Co. KG)

  • Xiaoli Chen

    (Novo Nordisk Research Centre China)

  • Fang Zhang

    (Novo Nordisk Research Centre China
    Structure Therapeutics. 701 Gateway Blvd.)

  • Jesper V. Olsen

    (The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen)

  • Dan Han

    (Novo Nordisk Research Centre China)

  • Mads Grønborg

    (Global Research Technologies, Novo Nordisk A/S)

  • Ulrik Lichtenberg

    (Global Research Technologies, Novo Nordisk A/S
    The Novo Nordisk Foundation, Tuborg Havnevej 19)

Abstract

Peptides play important roles in regulating biological processes and form the basis of a multiplicity of therapeutic drugs. To date, only about 300 peptides in human have confirmed bioactivity, although tens of thousands have been reported in the literature. The majority of these are inactive degradation products of endogenous proteins and peptides, presenting a needle-in-a-haystack problem of identifying the most promising candidate peptides from large-scale peptidomics experiments to test for bioactivity. To address this challenge, we conducted a comprehensive analysis of the mammalian peptidome across seven tissues in four different mouse strains and used the data to train a machine learning model that predicts hundreds of peptide candidates based on patterns in the mass spectrometry data. We provide in silico validation examples and experimental confirmation of bioactivity for two peptides, demonstrating the utility of this resource for discovering lead peptides for further characterization and therapeutic development.

Suggested Citation

  • Christian T. Madsen & Jan C. Refsgaard & Felix G. Teufel & Sonny K. Kjærulff & Zhe Wang & Guangjun Meng & Carsten Jessen & Petteri Heljo & Qunfeng Jiang & Xin Zhao & Bo Wu & Xueping Zhou & Yang Tang &, 2022. "Combining mass spectrometry and machine learning to discover bioactive peptides," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34031-z
    DOI: 10.1038/s41467-022-34031-z
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    References listed on IDEAS

    as
    1. Anna Secher & Christian D. Kelstrup & Kilian W. Conde-Frieboes & Charles Pyke & Kirsten Raun & Birgitte S. Wulff & Jesper V. Olsen, 2016. "Analytic framework for peptidomics applied to large-scale neuropeptide identification," Nature Communications, Nature, vol. 7(1), pages 1-10, September.
    2. Thomas D. Madsen & Lasse H. Hansen & John Hintze & Zilu Ye & Shifa Jebari & Daniel B. Andersen & Hiren J. Joshi & Tongzhong Ju & Jens P. Goetze & Cesar Martin & Mette M. Rosenkilde & Jens J. Holst & R, 2020. "An atlas of O-linked glycosylation on peptide hormones reveals diverse biological roles," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
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    Cited by:

    1. Erik Hartman & Fredrik Forsberg & Sven Kjellström & Jitka Petrlova & Congyu Luo & Aaron Scott & Manoj Puthia & Johan Malmström & Artur Schmidtchen, 2024. "Peptide clustering enhances large-scale analyses and reveals proteolytic signatures in mass spectrometry data," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Amanda L. Wiggenhorn & Hind Z. Abuzaid & Laetitia Coassolo & Veronica L. Li & Julia T. Tanzo & Wei Wei & Xuchao Lyu & Katrin J. Svensson & Jonathan Z. Long, 2023. "A class of secreted mammalian peptides with potential to expand cell-cell communication," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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