title: Phenotypic landscape of a bacterial cell.
abstract: The explosion of sequence information in bacteria makes developing high-throughput, cost-effective approaches to matching genes with phenotypes imperative. Using E. coli as proof of principle, we show that combining large-scale chemical genomics with quantitative fitness measurements provides a high-quality data set rich in discovery. Probing growth profiles of a mutant library in hundreds of conditions in parallel yielded > 10,000 phenotypes that allowed us to study gene essentiality, discover leads for gene function and drug action, and understand higher-order organization of the bacterial chromosome. We highlight new information derived from the study, including insights into a gene involved in multiple antibiotic resistance and the synergy between a broadly used combinatory antibiotic therapy, trimethoprim and sulfonamides. This data set, publicly available at http://ecoliwiki.net/tools/chemgen/, is a valuable resource for both the microbiological and bioinformatic communities, as it provides high-confidence associations between hundreds of annotated and uncharacterized genes as well as inferences about the mode of action of several poorly understood drugs.
authors.affiliation: University of California, San Francisco, 94143, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Nichols
authors.forename: Saunak
authors.initials: S
authors.lastname: Sen
authors.forename: Yoe Jin
authors.initials: YJ
authors.lastname: Choo
authors.forename: Pedro
authors.initials: P
authors.lastname: Beltrao
authors.forename: Matylda
authors.initials: M
authors.lastname: Zietek
authors.forename: Rachna
authors.initials: R
authors.lastname: Chaba
authors.forename: Sueyoung
authors.initials: S
authors.lastname: Lee
authors.forename: Krystyna M
authors.initials: KM
authors.lastname: Kazmierczak
authors.forename: Karis J
authors.initials: KJ
authors.lastname: Lee
authors.forename: Angela
authors.initials: A
authors.lastname: Wong
authors.forename: Michael
authors.initials: M
authors.lastname: Shales
authors.forename: Susan
authors.initials: S
authors.lastname: Lovett
authors.forename: Malcolm E
authors.initials: ME
authors.lastname: Winkler
authors.forename: Nevan J
authors.initials: NJ
authors.lastname: Krogan
authors.forename: Athanasios
authors.initials: A
authors.lastname: Typas
authors.forename: Carol A
authors.initials: CA
authors.lastname: Gross
mesh_terms: D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D016680:Genome, Bacterial; D023281:Genomics; D009154:Mutation