Systematic quantification of gene interactions by phenotypic array analysis.
A phenotypic array method, developed for quantifying cell growth, was applied to the haploid and homozygous diploid yeast deletion strain sets. A growth index was developed to screen for non-additive interacting effects between gene deletion and induced perturbations. From a genome screen for hydroxyurea (HU) chemical-genetic interactions, 298 haploid deletion strains were selected for further analysis. The strength of interactions was quantified using a wide range of HU concentrations affecting reference strain growth. The selectivity of interaction was determined by comparison with drugs targeting other cellular processes. Bio-modules were defined as gene clusters with shared strength and selectivity of interaction profiles. The functions and connectivity of modules involved in processes such as DNA repair, protein secretion and metabolic control were inferred from their respective gene composition. The work provides an example of, and a general experimental framework for, quantitative analysis of gene interaction networks that buffer cell growth.
Hartman
John L
JL
Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA. jhartman@fhcrc.org
Tippery
Nicholas P
NP
D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D004171:Diploidy; D017353:Gene Deletion; D020869:Gene Expression Profiling / Q000379:methods* / Q000706:statistics & numerical data; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects / Q000235:genetics*; D005800:Genes, Fungal / Q000235:genetics*; D006238:Haploidy; D006918:Hydroxyurea / Q000494:pharmacology; D008825:Miconazole / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods* / Q000706:statistics & numerical data; D010641:Phenotype; D015203:Reproducibility of Results; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D008825:Miconazole; D020122:tert-Butylhydroperoxide; D006918:Hydroxyurea