@article{7b9b66e12125453ba1bf69685d921eb2,
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.",
author = "Nichols, {Robert J.} and Saunak Sen and Choo, {Yoe Jin} and Pedro Beltrao and Matylda Zietek and Rachna Chaba and Sueyoung Lee and Kazmierczak, {Krystyna M.} and Lee, {Karis J.} and Angela Wong and Michael Shales and Susan Lovett and Winkler, {Malcolm E.} and Krogan, {Nevan J.} and Athanasios Typas and Gross, {Carol A.}",
note = "Funding Information: We thank R. Kishony, J. Weissman, A. Hochschild, and R.G. Martin for critically reading this manuscript; J. Hu and P. Thomas for hosting these data on E. coli Wiki; C. Raetz for CHIR-090 and M. Gottesman for Bicyclomycin; H. Mori for the Keio Collection; G. Storz for sharing the sRNA deletion library prior to publication; J.Greenblatt and A. Emili for SPA-tagged alleles; W. Margolin, R. Misra, T. Silhavy, and B. Palsson for mutants; and T. Baker and R. Sauer for controllable degradation plasmids. This work was supported by NIH R01 GM085697 and ARRA GM085697-01S1 to C.A.G. and N.J.K.; NIH R01 GM036278 to C.A.G.; NIH K99GM092984 to A.T.; NIH AI060744 to M.E.W.; NIH GM078338 to S.S.; NIH F31 DE020206-01 and NIH T32 DE007306 (R.J.N. support); European Molecular Biology Organization long-term fellowship (to A.T.); and Human Frontier Science Program Long-Term Postdoctoral Fellowship (to P.B.). In loving memory of S.R. Bartlett and J.T. Blair. ",
year = "2011",
month = jan,
day = "7",
doi = "10.1016/j.cell.2010.11.052",
language = "English",
volume = "144",
pages = "143--156",
journal = "Cell",
issn = "0092-8674",
publisher = "Elsevier B.V.",
number = "1",
}