title: Quantitative analysis of fitness and genetic interactions in yeast on a genome scale.
abstract: Global quantitative analysis of genetic interactions is a powerful approach for deciphering the roles of genes and mapping functional relationships among pathways. Using colony size as a proxy for fitness, we developed a method for measuring fitness-based genetic interactions from high-density arrays of yeast double mutants generated by synthetic genetic array (SGA) analysis. We identified several experimental sources of systematic variation and developed normalization strategies to obtain accurate single- and double-mutant fitness measurements, which rival the accuracy of other high-resolution studies. We applied the SGA score to examine the relationship between physical and genetic interaction networks, and we found that positive genetic interactions connect across functionally distinct protein complexes revealing a network of genetic suppression among loss-of-function alleles.
authors.affiliation: Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada. brenda.andrews@utoronto.ca
authors.forename: Anastasia
authors.initials: A
authors.lastname: Baryshnikova
authors.forename: Michael
authors.initials: M
authors.lastname: Costanzo
authors.forename: Yungil
authors.initials: Y
authors.lastname: Kim
authors.forename: Huiming
authors.initials: H
authors.lastname: Ding
authors.forename: Judice
authors.initials: J
authors.lastname: Koh
authors.forename: Kiana
authors.initials: K
authors.lastname: Toufighi
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Youn
authors.forename: Jiongwen
authors.initials: J
authors.lastname: Ou
authors.forename: Bryan-Joseph
authors.initials: BJ
authors.lastname: San Luis
authors.forename: Sunayan
authors.initials: S
authors.lastname: Bandyopadhyay
authors.forename: Matthew
authors.initials: M
authors.lastname: Hibbs
authors.forename: David
authors.initials: D
authors.lastname: Hess
authors.forename: Anne-Claude
authors.initials: AC
authors.lastname: Gingras
authors.forename: Gary D
authors.initials: GD
authors.lastname: Bader
authors.forename: Olga G
authors.initials: OG
authors.lastname: Troyanskaya
authors.forename: Grant W
authors.initials: GW
authors.lastname: Brown
authors.forename: Brenda
authors.initials: B
authors.lastname: Andrews
authors.forename: Charles
authors.initials: C
authors.lastname: Boone
authors.forename: Chad L
authors.initials: CL
authors.lastname: Myers
mesh_terms: D000465:Algorithms; D015966:Gene Expression Regulation, Fungal; D056084:Genetic Fitness; D016681:Genome, Fungal; D055106:Genome-Wide Association Study / Q000379:methods; D016296:Mutagenesis; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D014466:Ultraviolet Rays; D015003:Yeasts / Q000235:genetics* / Q000528:radiation effects