Journal
NATURE COMMUNICATIONS
Volume 13, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-34031-z
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Funding
- Novo Nordisk Foundation [NNF14CC0001]
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The authors use a machine learning framework to predict mammalian peptide candidates from large-scale tissue-specific mass spectrometry data. This resource provides useful information for discovering lead peptides for further characterization and therapeutic development.
Bioactive peptides regulate many physiological functions but progress in discovering them has been slow. Here, the authors use a machine learning framework to predict mammalian peptide candidates from the global and local structure of large-scale tissue-specific mass spectrometry data. 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.
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