Cell 102, 109-126 (2000).

(Note: Current Rosetta Inpharmatics employees are shown in boldface type.)

Timothy R. Hughes, Matthew J. Marton, Allan R. Jones, Christopher J. Roberts, Roland Stoughton, Christopher D. Armour, Holly A. Bennett, Ernest Coffey, Hongyue Dai, Yudong D. He, Matthew J. Kidd, Amy M. King, Michael R. Meyer, David Slade, Pek Y. Lum, Sergey B. Stepaniants, Daniel D. Shoemaker, Daniel Gachotte, Kalpana Chakraburtty, Julian Simon, Martin Bard, and Stephen H. Friend

Abstract

Ascertaining the impact of uncharacterized perturbations on the cell is a fundamental problem in biology. Here, we describe how a single assay can be used to monitor hundreds of different cellular functions simultaneously. We constructed a reference database or 'compendium' of expression profiles corresponding to 300 diverse mutations and chemical treatments in S. cerevisiae, and we show that the cellular pathways affected can be determined by pattern matching, even among very subtle profiles. The utility of this approach is validated by examining profiles caused by deletions of uncharacterized genes: we identify and experimentally confirm that eight previously uncharacterized open reading frames encode proteins required for sterol metabolism, cell wall function, mitochondrial respiration, or protein synthesis. We also show that the compendium can be used to characterize pharmacological perturbations by identifying a previously unknown target of the commonly used drug dyclonine.

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