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Machine learning reveals genes impacting oxidative stress resistance across yeasts
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Journal Article
Machine learning reveals genes impacting oxidative stress resistance across yeasts
2025
Overview
Reactive oxygen species (ROS) are highly reactive molecules encountered by yeasts during routine metabolism and during interactions with other organisms, including host infection. Here, we characterize the variation in resistance to the ROS-inducing compound
tert
-butyl hydroperoxide across the ancient yeast subphylum Saccharomycotina and use machine learning (ML) to identify gene families whose sizes are predictive of ROS resistance. The most predictive features are enriched in gene families related to cell wall organization and include two reductase gene families. We estimate the quantitative contributions of features to each species’ classification to guide experimental validation and show that overexpression of the old yellow enzyme (OYE) reductase increases ROS resistance in
Kluyveromyces lactis
, while
Saccharomyces cerevisiae
mutants lacking multiple mannosyltransferase-encoding genes are hypersensitive to ROS. Altogether, this work provides a framework for how ML can uncover genetic mechanisms underlying trait variation across diverse species and inform trait manipulation for clinical and biotechnological applications.
Yeasts are exposed to oxidative stress during routine metabolism, bioproduction, and interactions with other organisms. Here, the authors use a machine learning classifier to identify genes that are predictive of resistance to oxidative stress across diverse yeast species.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 45/47
/ Enzymes
/ Fungal Proteins - metabolism
/ Gene Expression Regulation, Fungal
/ Genes
/ Genomics
/ Humanities and Social Sciences
/ Kluyveromyces - drug effects
/ Mannosyltransferases - genetics
/ Mannosyltransferases - metabolism
/ Oxidative Stress - drug effects
/ Oxidoreductases - metabolism
/ Reactive Oxygen Species - metabolism
/ Saccharomyces cerevisiae - drug effects
/ Saccharomyces cerevisiae - genetics
/ Saccharomyces cerevisiae - metabolism
/ Science
/ tert-Butylhydroperoxide - pharmacology
/ Yeast
