Chemogenomic profiling: Identifying the functional interactions of small molecules in yeast

We demonstrate the efficacy of a genome-wide protocol in yeastthat allows the identification of those gene products that functionallyinteract with small molecules and result in the inhibition ofcellular proliferation. Here we present results from screening 10diverse compounds in 80 genome-wide experiments against thecomplete collection of heterozygous yeast deletion strains. Thesecompounds include anticancer and antifungal agents, statins, alverinecitrate, and dyclonine. In several cases, we identified previouslyknown interactions; furthermore, in each case, our analysisrevealed novel cellular interactions, even when the relationshipbetween a compound and its cellular target had been well established.In addition, we identified a chemical core structure sharedamong three therapeutically distinct compounds that inhibit theERG24 heterozygous deletion strain, demonstrating that cells mayrespond similarly to compounds of related structure. The ability toidentify on-and-off target effects in vivo is fundamental to understanding the cellular response to small-molecule perturbants