Email updates

Keep up to date with the latest news and content from Genome Biology and BioMed Central.

Open Access Method

Systematic quantification of gene interactions by phenotypic array analysis

John L Hartman* and Nicholas P Tippery

Author Affiliations

Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA

For all author emails, please log on.

Genome Biology 2004, 5:R49  doi:10.1186/gb-2004-5-7-r49

Published: 29 June 2004

Abstract

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.