TY - JOUR
T1 - Identification of drug targets by chemogenomic and metabolomic profiling in yeast
AU - Wu, Manhong
AU - Zheng, Ming
AU - Zhang, Weiruo
AU - Suresh, Sundari
AU - Schlecht, Ulrich
AU - Fitch, William L.
AU - Aronova, Sofia
AU - Baumann, Stephan
AU - Davis, Ronald
AU - St.Onge, Robert
AU - Dill, David L.
AU - Peltz, Gary
N1 - KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: G.P. and M. W. were partially supported by funding from a transformative RO1 award (1R01DK090992-01). D. L. D. and W.Z. were supported by a King Abdullah University of Science and Technology (KAUST) research grant under the KAUST Stanford Academic Excellence Alliance program. S. S., U. S., R. D. and B. S. were partially supported by funding from the National Human Genome Research Institute (2R01HG003317-05) provided to R.D.
This publication acknowledges KAUST support, but has no KAUST affiliated authors.
PY - 2012/12
Y1 - 2012/12
N2 - 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. BASIC 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. RESULTS AND CONCLUSION: 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. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.
AB - 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. BASIC 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. RESULTS AND CONCLUSION: 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. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.
UR - http://hdl.handle.net/10754/598548
UR - http://journals.lww.com/01213011-201212000-00006
UR - http://www.scopus.com/inward/record.url?scp=84870362521&partnerID=8YFLogxK
U2 - 10.1097/FPC.0b013e32835aa888
DO - 10.1097/FPC.0b013e32835aa888
M3 - Article
C2 - 23076370
SN - 1744-6872
VL - 22
SP - 877
EP - 886
JO - Pharmacogenetics and Genomics
JF - Pharmacogenetics and Genomics
IS - 12
ER -