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Mapping the Cellular Response to Small Molecules Using Chemogenomic Fitness Signatures

2014; American Association for the Advancement of Science; Volume: 344; Issue: 6180 Linguagem: Inglês

10.1126/science.1250217

1095-9203

Anna Y. Lee, Robert P. St.Onge, Michael 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 Fung, Malene L. Urbanus, Marinella Gebbia, Elena Lissina, Molly Miranda, Jennifer Chiang, Ana M. 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,

Fungal and yeast genetics research

Yeasty HIPHOP In order to identify how chemical compounds target genes and affect the physiology of the cell, tests of the perturbations that occur when treated with a range of pharmacological chemicals are required. By examining the haploinsufficiency profiling (HIP) and homozygous profiling (HOP) chemogenomic platforms, Lee et al. (p. 208 ) analyzed the response of yeast to thousands of different small molecules, with genetic, proteomic, and bioinformatic analyses. Over 300 compounds were identified that targeted 121 genes within 45 cellular response signature networks. These networks were used to extrapolate the likely effects of related chemicals, their impact upon genetic pathways, and to identify putative gene functions.