biostudies-literatureFu CNIAID NIH HHSFoundation for the National Institutes of HealthCIHR6497https://www.ebi.ac.uk/biostudies/studies/S-EPMC8586148biostudies-literatureUnknown12(1)Fungal pathogens pose a global threat to human health, with Candida albicans among the leading killers. Systematic analysis of essential genes provides a powerful strategy to discover potential antifungal targets. Here, we build a machine learning model to generate genome-wide gene essentiality predictions for C. albicans and expand the largest functional genomics resource in this pathogen (the GRACE collection) by 866 genes. Using this model and chemogenomic analyses, we define the function of three uncharacterized essential genes with roles in kinetochore function, mitochondrial integrity, and translation, and identify the glutaminyl-tRNA synthetase Gln4 as the target of N-pyrimidinyl-β-thiophenylacrylamide (NP-BTA), an antifungal compound.Nature communicationsLeveraging machine learning essentiality predictions and chemogenomic interactions to identify antifungal targets.PMC8586148R01 AI127375FDN 143301FDN-154288R01AI127375Veri AOO'Meara TRO'Meara MJLin ZYXue ARevie NMBoone CPolvi EJNoble SListon SDIyer KRMyers CLYashiroda YWong CCowen LELash EHou JFu CZhang XRobbins NVanderSluis BYan HGingras ACfalseLeveraging machine learning essentiality predictions and chemogenomic interactions to identify antifungal targets.Fungal pathogens pose a global threat to human health, with Candida albicans among the leading killers. Systematic analysis of essential genes provides a powerful strategy to discover potential antifungal targets. Here, we build a machine learning model to generate genome-wide gene essentiality predictions for C. albicans and expand the largest functional genomics resource in this pathogen (the GRACE collection) by 866 genes. Using this model and chemogenomic analyses, we define the function of three uncharacterized essential genes with roles in kinetochore function, mitochondrial integrity, and translation, and identify the glutaminyl-tRNA synthetase Gln4 as the target of N-pyrimidinyl-β-thiophenylacrylamide (NP-BTA), an antifungal compound.2021-01-01T00:00:00Z2021 Nov2024-11-21T06:03:09.6Z2022-02-11T12:59:22.438ZS-EPMC85861483476426910.1038/s41467-021-26850-3