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Machine learning reveals genes impacting oxidative stress resistance across yeasts

Journal Article · · Nature Communications
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.
Research Organization:
Univ. of Wisconsin, Madison, WI (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
Grant/Contract Number:
SC0018409
OSTI ID:
2570914
Journal Information:
Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 16; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English

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