Identification of drug targets by chemogenomic and metabolomic profiling in yeast.
OBJECTIVE
To advance our understanding of disease biology, the characterization of the molecular target for clinically proven or new drugs is very important. Because of its simplicity and the availability of strains with individual deletions in all of its genes, chemogenomic profiling in yeast has been used to identify drug targets. As measurement of drug-induced changes in cellular metabolites can yield considerable information about the effects of a drug, we investigated whether combining chemogenomic and metabolomic profiling in yeast could improve the characterization of drug targets.


METHODS
We used chemogenomic and metabolomic profiling in yeast to characterize the target for five drugs acting on two biologically important pathways. A novel computational method that uses a curated metabolic network was also developed, and it was used to identify the genes that are likely to be responsible for the metabolomic differences found.


CONCLUSIONS
The combination of metabolomic and chemogenomic profiling, along with data analyses carried out using a novel computational method, could robustly identify the enzymes targeted by five drugs. Moreover, this novel computational method has the potential to identify genes that are causative of metabolomic differences or drug targets.
Department of Anesthesia, Stanford University School of Medicine, Stanford University, Stanford, California 94305, USA.
Manhong
M
Wu
Ming
M
Zheng
Weiruo
W
Zhang
Sundari
S
Suresh
Ulrich
U
Schlecht
William L
WL
Fitch
Sofia
S
Aronova
Stephan
S
Baumann
Ronald
R
Davis
Robert
R
St Onge
David L
DL
Dill
Gary
G
Peltz
D019295:Computational Biology; D016503:Drug Delivery Systems; D020869:Gene Expression Profiling; D053858:Metabolic Networks and Pathways; D055432:Metabolomics; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*