Quantitative analysis of fitness and genetic interactions in yeast on a genome scale

Publication Type  Journal Article
Author  Baryshnikova A, Costanzo M, Kim Y, Ding H, Koh J, Toufighi K, Youn J, Ou J, Luis B, Bandyopadhyay S, Hibbs MA, Hess DC, Gingras A, Bader GD, Troyanskaya OG, Brown GW, Andrews B, Boone C, Myers CL
Year of Publication  2010
Journal  Nature Methods
Volume  7
Issue  12
Pagination  1017–24
Date Published  Dec
Publication Language  eng
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.

URL  http://www.nature.com/nmeth/journal/v7/n12/full/nmeth.1534.html
Citation Key  Baryshnikova:2010p4397