Access

Article

Nature Methods 5, 789–795 (1 September 2008) | doi:10.1038/nmeth.1239

eSGA: E. coli synthetic genetic array analysis

Gareth Butland , Mohan Babu , J Javier D|[iacute]|az-Mej|[iacute]|a , Fedyshyn Bohdana , Sadhna Phanse , Barbara Gold , Wenhong Yang , Joyce Li , Alla G Gagarinova , Oxana Pogoutse , Hirotada Mori , Barry L Wanner , Henry Lo , Jas Wasniewski , Constantine Christopoulos , Mehrab Ali , Pascal Venn , Anahita Safavi-Naini , Natalie Sourour , Simone Caron , Ja-Yeon Choi , Ludovic Laigle , Anaies Nazarians-Armavil , Avnish Deshpande , Sarah Joe , Kirill A Datsenko , Natsuko Yamamoto , Brenda J Andrews , Charles Boone , Huiming Ding , Bilal Sheikh , Gabriel Moreno-Hagelsieb , Jack F Greenblatt & Andrew Emili

Physical and functional interactions define the molecular organization of the cell. Genetic interactions, or epistasis, tend to occur between gene products involved in parallel pathways or interlinked biological processes. High-throughput experimental systems to examine genetic interactions on a genome-wide scale have been devised for Saccharomyces cerevisiae, Schizosaccharomyces pombe, Caenorhabditis elegans and Drosophila melanogaster, but have not been reported previously for prokaryotes. Here we describe the development of a quantitative screening procedure for monitoring bacterial genetic interactions based on conjugation of Escherichia coli deletion or hypomorphic strains to create double mutants on a genome-wide scale. The patterns of synthetic sickness and synthetic lethality (aggravating genetic interactions) we observed for certain double mutant combinations provided information about functional relationships and redundancy between pathways and enabled us to group bacterial gene products into functional modules. NOTE: In the version of this article initially published online two author names (Gabriel Moreno-Hagelseib and Constantine Christopolous) were spelled incorrectly. The correct author names are Gabriel Moreno-Hagelsieb and Constantine Christopoulos. The error has been corrected for the print, PDF and HTML versions of this article.