Reference: Ericson E, et al. (2010) Exploring gene function and drug action using chemogenomic dosage assays. Methods Enzymol 470:233-55

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Abstract


In this chapter, we describe a series of genome-wide, cell-based assays that provide a solid basis for understanding drug-gene interactions, gene function, and for defining the mechanism of action of small molecules. Each of these assays takes advantage of the ability to grow complex pools competitively and to use high-density microarrays that report the results of such screens. The assays described here take advantage of alterations in gene dosage of Saccharomyces cerevisiae, and include HIP (haploinsufficiency profiling), HOP (homozygous profiling), and MSP (multicopy suppression profiling) as genetic tools to understand gene function and drug mechanism. The common experimental theme is that, in each assay, strains are pooled and screened in parallel to investigate the relative contribution of each gene product to sensitivity or resistance to a drug or environmental perturbation across the genome in a single assay. Further, the compendium of results from these screens can inform large-scale network analysis of genetic function, gene-gene interactions, and mechanism of drug action.

Reference Type
Journal Article | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov't
Authors
Ericson E, Hoon S, St Onge RP, Giaever G, Nislow C
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Gene Ontology Annotations


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Gene/Complex Qualifier Gene Ontology Term Aspect Annotation Extension Evidence Method Source Assigned On Reference

Phenotype Annotations


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Gene Phenotype Experiment Type Mutant Information Strain Background Chemical Details Reference

Disease Annotations


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Gene Disease Ontology Term Qualifier Evidence Method Source Assigned On Reference

Regulation Annotations


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Regulator Target Direction Regulation Of Happens During Method Evidence

Post-translational Modifications


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Site Modification Modifier Reference

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Genetic Interactions

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Interactor Interactor Allele Assay Annotation Action Phenotype SGA score P-value Source Reference

Physical Interactions

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Interactor Interactor Assay Annotation Action Modification Source Reference

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Gene Species Gene ID Strain background Direction Details Source Reference