Identification of drug targets by chemogenomic and metabolomic profiling in yeast
Fitch, William L.
Dill, David L.
Permanent link to this recordhttp://hdl.handle.net/10754/598548
MetadataShow full item record
AbstractOBJECTIVE: 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.
CitationWu M, Zheng M, Zhang W, Suresh S, Schlecht U, et al. (2012) Identification of drug targets by chemogenomic and metabolomic profiling in yeast. Pharmacogenetics and Genomics 22: 877–886. Available: http://dx.doi.org/10.1097/FPC.0b013e32835aa888.
SponsorsG.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.
JournalPharmacogenetics and Genomics
CollectionsPublications Acknowledging KAUST Support
- Yeast as a tool to uncover the cellular targets of drugs.
- Authors: Sturgeon CM, Kemmer D, Anderson HJ, Roberge M
- Issue date: 2006 Mar
- High-resolution chemical dissection of a model eukaryote reveals targets, pathways and gene functions.
- Authors: Hoepfner D, Helliwell SB, Sadlish H, Schuierer S, Filipuzzi I, Brachat S, Bhullar B, Plikat U, Abraham Y, Altorfer M, Aust T, Baeriswyl L, Cerino R, Chang L, Estoppey D, Eichenberger J, Frederiksen M, Hartmann N, Hohendahl A, Knapp B, Krastel P, Melin N, Nigsch F, Oakeley EJ, Petitjean V, Petersen F, Riedl R, Schmitt EK, Staedtler F, Studer C, Tallarico JA, Wetzel S, Fishman MC, Porter JA, Movva NR
- Issue date: 2014 Feb-Mar
- Identifying drug active pathways from gene networks estimated by gene expression data.
- Authors: Tamada Y, Imoto S, Tashiro K, Kuhara S, Miyano S
- Issue date: 2005
- A latent variable model for chemogenomic profiling.
- Authors: Flaherty P, Giaever G, Kumm J, Jordan MI, Arkin AP
- Issue date: 2005 Aug 1
- Computational identification of altered metabolism using gene expression and metabolic pathways.
- Authors: Nam H, Lee J, Lee D
- Issue date: 2009 Jul 1