Functional Discovery via a Compendium of Expression Profiles

Rosetta Inpharmatics, Inc., Kirkland, Washington 98034, USA.
Cell (Impact Factor: 33.12). 08/2000; 102(1):109-26. DOI: 10.1016/S0092-8674(00)00015-5
Source: PubMed

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 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 novel target of the commonly used drug dyclonine.

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Available from: Christopher D Armour, Aug 31, 2015
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    • "A compendium of transcriptional profiles or signatures of gene-deletion strains under various growth conditions is useful for function discovery (Hughes et al. 2000). Hence, we wanted to investigate whether there was a unique transcriptional signature in kinase-deletion strains defective in iodine vapor staining or sexual development (hereafter sexual development) and G0 arrest. "
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    • "For example, publications that reference the YKO collections and have themselves been cited >1000 times (Figure 3) include the yeast tandem affinity purification (TAP-tagged) collection (Krogan et al. 2006), the GFP collection (Ghaemmaghami et al. 2003), and genome-scale two-hybrid studies (Ito et al. 2001). Other highly cited articles inspired by the YKO resource include novel methods for mutant construction in other organisms [e.g., Arabidopsis thaliana (Alonso et al. 2003) and Escherichia coli mutant collections (Baba et al. 2006), new technologies (genome-scale protein-complex mass spectrometry, protein microarrays (Zhu et al. 2001), digenetic interactions by SGA (Tong et al. 2001), and large-scale expression studies (Hughes et al. 2000a)]. "
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