Parsons AB~Boone C, 2004

Pubmed ID 14661025
Title Integration of chemical-genetic and genetic interaction data links bioactive compounds to cellular target pathways.
Authors Ainslie B Parsons, Renée L Brost, Huiming Ding, Zhijian Li, Chaoying Zhang, Bilal Sheikh, Grant W Brown, Patricia M Kane, Timothy R Hughes, Charles Boone
Abstract Bioactive compounds can be valuable research tools and drug leads, but it is often difficult to identify their mechanism of action or cellular target. Here we investigate the potential for integration of chemical-genetic and genetic interaction data to reveal information about the pathways and targets of inhibitory compounds. Taking advantage of the existing complete set of yeast haploid deletion mutants, we generated drug-hypersensitivity (chemical-genetic) profiles for 12 compounds. In addition to a set of compound-specific interactions, the chemical-genetic profiles identified a large group of genes required for multidrug resistance. In particular, yeast mutants lacking a functional vacuolar H(+)-ATPase show multidrug sensitivity, a phenomenon that may be conserved in mammalian cells. By filtering chemical-genetic profiles for the multidrug-resistant genes and then clustering the compound-specific profiles with a compendium of large-scale genetic interaction profiles, we were able to identify target pathways or proteins. This method thus provides a powerful means for inferring mechanism of action.
Citation Nat. Biotechnol. 2004; 22:62-9

Datasets

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Paper Phenotype Condition Medium Collection Tested mutants Data Details
Parsons AB~Boone C, 2004 growth (colony size) tacrolimus (anhydrous) [2 ug/ml] SC hap a ~4,700 Discrete
Parsons AB~Boone C, 2004 growth (colony size) cyclosporin A [100 ug/ml] SC hap a ~4,700 Discrete
Parsons AB~Boone C, 2004 growth (colony size) hydroxyurea [100 mM] YPD hap a ~4,700 Discrete
Parsons AB~Boone C, 2004 growth (colony size) camptothecin [15 ug/ml] YPD hap a ~4,700 Discrete
Parsons AB~Boone C, 2004 growth (colony size) fluconazole [15 ug/ml] YPD hap a ~4,700 Discrete
Parsons AB~Boone C, 2004 growth (colony size) tunicamycin [5 ug/ml] YPD hap a ~4,700 Discrete
Parsons AB~Boone C, 2004 growth (colony size) wortmannin [1.3 ug/ml] YPD hap a ~4,700 Discrete
Parsons AB~Boone C, 2004 growth (colony size) caffeine [0.15%] SC hap a ~4,700 Discrete
Parsons AB~Boone C, 2004 growth (colony size) sirolimus [0.015 ug/ml] YPD hap a ~4,700 Discrete
Parsons AB~Boone C, 2004 growth (colony size) benomyl [15 ug/ml] YPD hap a ~4,700 Discrete
Parsons AB~Boone C, 2004 growth (colony size) sulfometuron methyl [3 ug/ml] SC hap a ~4,700 Discrete
Parsons AB~Boone C, 2004 growth (colony size) cycloheximide [0.1 ug/ml] YPD hap a ~4,700 Discrete

Curation history

Data

Feb. 20, 2014 Loaded.

Tested strains

Feb. 20, 2014 Request sent.
May 12, 2016 Request abandoned.