ArticleCell reports2013
A functional variomics tool for discovering drug-resistance genes and drug targets.
Article in Cell reports, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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Who cites it
37 citing papers in PubMed, 70 citations in OpenAlex.
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- Genomic Approaches to Antifungal Drug Target Identification and Validation.Annual review of microbiology · 2022Review
- E-site drug specificity of the human pathogenScience advances · 2022Article
- The NPR/Hal family of protein kinases in yeasts: biological role, phylogeny and regulation under environmental challenges.Computational and structural biotechnology journal · 2022Review
- Natural Deep Eutectic Extracts of Propolis,Oxidative medicine and cellular longevity · 2022Article
- Article
- Discovering new biology with drug-resistance alleles.Nature chemical biology · 2021Review
- Advances in fungal chemical genomics for the discovery of new antifungal agents.Annals of the New York Academy of Sciences · 2021Review
- Phosphorylation of mRNA-Binding Proteins Puf1 and Puf2 by TORC2-Activated Protein Kinase Ypk1 Alleviates Their Repressive Effects.Membranes · 2021Article
- Engineered yeast tolerance enables efficient production from toxified lignocellulosic feedstocks.Science advances · 2021Article
- Identification and characterization of hippuristanol-resistant mutants reveals eIF4A1 dependencies within mRNA 5' leader regions.Nucleic acids research · 2020Article
- CPSF3-dependent pre-mRNA processing as a druggable node in AML and Ewing's sarcoma.Nature chemical biology · 2020Article
- Genomewide Elucidation of Drug Resistance Mechanisms for Systemically Used Antifungal Drugs Amphotericin B, Caspofungin, and Voriconazole in the Budding Yeast.Antimicrobial agents and chemotherapy · 2019Article
- Discovery of a ZIP7 inhibitor from a Notch pathway screen.Nature chemical biology · 2019Article
- From Yeast to Humans: Leveraging New Approaches in Yeast to Accelerate Discovery of Therapeutic Targets for Synucleinopathies.Methods in molecular biology (Clifton, N.J.) · 2019Article
- Chemogenomic profiling in yeast reveals antifungal mode-of-action of polyene macrolactam auroramycin.PloS one · 2019Article
- Target Identification and Mechanism of Action of Picolinamide and Benzamide Chemotypes with Antifungal Properties.Cell chemical biology · 2018Article
- Stendomycin selectively inhibits TIM23-dependent mitochondrial protein import.Nature chemical biology · 2017Article
- Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
Comprehensive discovery of genetic mechanisms of drug resistance and identification of in vivo drug targets represent significant challenges. Here we present a functional variomics technology in the model organism Saccharomyces cerevisiae. This tool analyzes numerous genetic variants and effectively tackles both problems simultaneously. Using this tool, we discovered almost all genes that, due to mutations or modest overexpression, confer resistance to rapamycin, cycloheximide, and amphotericin B. Most significant among the resistance genes were drug targets, including multiple targets of a given drug. With amphotericin B, we discovered the highly conserved membrane protein Pmp3 as a potent resistance factor and a possible target. Widespread application of this tool should allow rapid identification of conserved resistance mechanisms and targets of many more compounds. New genes and alleles that confer resistance to other stresses can also be discovered. Similar tools in other systems, such as human cell lines, will also be useful.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.