Leveraging machine learning essentiality predictions and chemogenomic interactions to identify antifungal targets

Ci Fu, Xiang Zhang, Amanda O. Veri, Kali R. Iyer, Emma Lash, Alice Xue, Huijuan Yan, Nicole M. Revie, Cassandra Wong, Zhen-Yuan Lin, Elizabeth J. Polvi, Sean D. Liston, Benjamin VanderSluis, Jing Hou, Yoko Yashiroda, Anne-Claude Gingras, Charles Boone, Teresa R. O’Meara, Matthew J. O’Meara, Suzanne Noble, Nicole Robbins, Chad L. Myers () and Leah E. Cowen ()
Additional contact information
Ci Fu: University of Toronto
Xiang Zhang: University of Minnesota
Amanda O. Veri: University of Toronto
Kali R. Iyer: University of Toronto
Emma Lash: University of Toronto
Alice Xue: University of Toronto
Huijuan Yan: UCSF School of Medicine
Nicole M. Revie: University of Toronto
Cassandra Wong: Lunenfeld-Tanenbaum Research Institute, Sinai Health System
Zhen-Yuan Lin: Lunenfeld-Tanenbaum Research Institute, Sinai Health System
Elizabeth J. Polvi: University of Toronto
Sean D. Liston: University of Toronto
Benjamin VanderSluis: University of Minnesota
Jing Hou: University of Toronto
Yoko Yashiroda: RIKEN Center for Sustainable Resource Science
Anne-Claude Gingras: University of Toronto
Charles Boone: University of Toronto
Teresa R. O’Meara: University of Michigan Medical School
Matthew J. O’Meara: University of Michigan
Suzanne Noble: UCSF School of Medicine
Nicole Robbins: University of Toronto
Chad L. Myers: University of Minnesota
Leah E. Cowen: University of Toronto

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: Abstract 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26850-3

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DOI: 10.1038/s41467-021-26850-3

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