Combining mass spectrometry and machine learning to discover bioactive peptides
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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.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 6235 |
| Tidsskrift | Nature Communications |
| Vol/bind | 13 |
| Antal sider | 17 |
| ISSN | 2041-1723 |
| DOI | |
| Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
We thank Dr. L.G. Grunnet, Dr. C. Rescan, and I.P. Eliasen for Islet and GSIS assay support. Dr. T. Frogne is acknowledged for the creation of the INS1E luciferase clone21 cell line. Dr. J.O. Samuelsson and Professor J. Cox for data logistics and search engine support. Y.T. Lam, A.K. Hansen, and M.B. Larsen are thanked for technical MS support. Y. Gan is thanked for E. coli expression support. Y. Wu, X. Yang, X. Sun, Y. Dai, Y. LV are all thanked for in-vitro support, and W. Yin, and H. Sun for in-vivo support. B. Wang and J. Jin are thanked for plasma analysis support. J. Yang and K.A. Richard are thanked for invaluable data support. The Novo Nordisk Foundation (Grant agreement NNF14CC0001) supports J.V. Olsen’s work at the Novo Nordisk Foundation Center for Protein Research.
Funding Information:
The authors declare the following competing interests: The authors are or have been working for Novo Nordisk A/S, a pharmaceutical company with commercial interest in bioactive peptides for the treatment of diabetes and obesity. All authors except J.C.R, F.G.T, U.L, and J.V.O. hold minor share portions as part of their employment in Novo Nordisk. J.V.O. consults for and has research funding from Novo Nordisk.
Publisher Copyright:
© 2022, The Author(s).
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