Functional discovery via a compendium of expression profiles

Ascertaining the impact of uncharacterized perturbations on the cell is a f undamental 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 co rresponding to 300 diverse mutations and chemical treatments in S. cerevisi ae, and we show that the cellular pathways affected can be determined by pa ttern matching, even among very subtle profiles. The utility of this approa ch is validated by examining profiles caused by deletions of uncharacterize d genes: we identify and experimentally confirm that eight uncharacterized open reading frames encode proteins required for sterol metabolism, cell wa ll function, mitochondrial respiration, or protein synthesis. We also show that the compendium can be used to characterize pharmacological perturbatio ns by identifying a novel target of the commonly used drug dyclonine.