Mapping the Cellular Response to Small Molecules Using Chemogenomic Fitness Signatures
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Kaiser_Mapping the.pdf
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1.28 MB
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Author(s)
Spear, Eric D.
Kaiser, Chris
Date Issued
April 2014
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Lee, A. Y., R. P. St.Onge, M. J. Proctor, I. M. Wallace, A. H. Nile, P. A. Spagnuolo, Y. Jitkova, et al. “Mapping the Cellular Response to Small Molecules Using Chemogenomic Fitness Signatures.” Science 344, no. 6180 (April 10, 2014): 208–211.
Version
Author's final manuscript
Abstract
Genome-wide characterization of the in vivo cellular response to perturbation is fundamental to understanding how cells survive stress. Identifying the proteins and pathways perturbed by small molecules affects biology and medicine by revealing the mechanisms of drug action. We used a yeast chemogenomics platform that quantifies the requirement for each gene for resistance to a compound in vivo to profile 3250 small molecules in a systematic and unbiased manner. We identified 317 compounds that specifically perturb the function of 121 genes and characterized the mechanism of specific compounds. Global analysis revealed that the cellular response to small molecules is limited and described by a network of 45 major chemogenomic signatures. Our results provide a resource for the discovery of functional interactions among genes, chemicals, and biological processes.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1126/science.1250217
