Article
Chemogenomic profiling: Identifying the functional interactions of small molecules in yeast
Proceedings of the National Academy of Sciences
(2004)
Abstract
We demonstrate the efficacy of a genome-wide protocol in yeast
that allows the identification of those gene products that functionally
interact with small molecules and result in the inhibition of
cellular proliferation. Here we present results from screening 10
diverse compounds in 80 genome-wide experiments against the
complete collection of heterozygous yeast deletion strains. These
compounds include anticancer and antifungal agents, statins, alverine
citrate, and dyclonine. In several cases, we identified previously
known interactions; furthermore, in each case, our analysis
revealed novel cellular interactions, even when the relationship
between a compound and its cellular target had been well established.
In addition, we identified a chemical core structure shared
among three therapeutically distinct compounds that inhibit the
ERG24 heterozygous deletion strain, demonstrating that cells may
respond similarly to compounds of related structure. The ability to
identify on-and-off target effects in vivo is fundamental to understanding the cellular response to small-molecule perturbants.
Keywords
- profiling,
- genetics,
- molecules,
- yeast
Disciplines
Publication Date
Winter January 20, 2004
DOI
10.1073/pnas.0307490100
Citation Information
Patrick Flaherty. "Chemogenomic profiling: Identifying the functional interactions of small molecules in yeast" Proceedings of the National Academy of Sciences Vol. 101 Iss. 3 (2004) p. 793 - 798 Available at: http://works.bepress.com/patrick-flaherty/2/