Mapping the cellular response to small molecules using chemogenomic fitness signatures

Anna Y. Lee, Robert P. St.Onge, Michael J. Proctor, Iain M. Wallace, Aaron H. Nile, Paul A. Spagnuolo, Yulia Jitkova, Marcela Gronda, Yan Wu, Moshe K. Kim, Kahlin Cheung-Ong, Nikko P. Torres, Eric D. Spear, Mitchell K.L. Han, Ulrich Schlecht, Sundari Suresh, Geoffrey Duby, Lawrence E. Heisler, Anuradha Surendra, Eula FungMalene L. Urbanus, Marinella Gebbia, Elena Lissina, Molly Miranda, Jennifer H. Chiang, Ana Maria Aparicio, Mahel Zeghouf, Ronald W. Davis, Jacqueline Cherfils, Marc Boutry, Chris A. Kaiser, Carolyn L. Cummins, William S. Trimble, Grant W. Brown, Aaron D. Schimmer, Vytas A. Bankaitis, Corey Nislow, Gary D. Bader, Guri Giaever

Research output: Contribution to journalArticlepeer-review

143 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)208-211
Number of pages4
JournalScience
Volume344
Issue number6180
DOIs
StatePublished - 2014
Externally publishedYes

ASJC Scopus subject areas

  • General

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