A Chemical Structure and Machine Learning Approach to Assess the Potential Bioactivity of Endogenous Metabolites and Their Association with Early Childhood Systemic Inflammation

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Metabolomics has gained much attention due to its potential to reveal molecular disease mechanisms and present viable biomarkers. This work uses a panel of untargeted serum metabolomes from 602 children from the COPSAC2010 mother–child cohort. The annotated part of the metabolome consists of 517 chemical compounds curated using automated procedures. We created a filtering method for the quantified metabolites using predicted quantitative structure–bioactivity relationships for the Tox21 database on nuclear receptors and stress response in cell lines. The metabolites measured in the children’s serums are predicted to affect specific targeted models, known for their significance in inflammation, immune function, and health outcomes. The targets from Tox21 have been used as targets with quantitative structure–activity relationships (QSARs). They were trained for ~7000 structures, saved as models, and then applied to the annotated metabolites to predict their potential bioactivities. The models were selected based on strict accuracy criteria surpassing random effects. After application, 52 metabolites showed potential bioactivity based on structural similarity with known active compounds from the Tox21 set. The filtered compounds were subsequently used and weighted by their bioactive potential to show an association with early childhood hs-CRP levels at six months in a linear model supporting a physiological adverse effect on systemic low-grade inflammation.

Original languageEnglish
Article number278
JournalMetabolites
Volume14
Issue number5
Number of pages16
ISSN2218-1989
DOIs
Publication statusPublished - 2024

Bibliographical note

Publisher Copyright:
© 2024 by the authors.

    Research areas

  • cortisol, cortisone, CRP, inflammation, metabolomics, QSAR, vitamin A

ID: 393632324