View source for PMID:21185072

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!align=left  |Citation
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'''Nichols, RJ, Sen, S, Choo, YJ, Beltrao, P, Zietek, M, Chaba, R, Lee, S, Kazmierczak, KM, Lee, KJ, Wong, A, Shales, M, Lovett, S, Winkler, ME, Krogan, NJ, Typas, A and Gross, CA'''  (2011) Phenotypic landscape of a bacterial cell.''Cell'' '''144''':143-56
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!align=left  |Abstract
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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.
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!align=left  |Links
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*[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21185072 PubMed]
*Online version:[http://dx.doi.org/10.1016/j.cell.2010.11.052 10.1016/j.cell.2010.11.052]
*[http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WSN-51SFHJD-1&_user=952835&_coverDate=01%2F07%2F2011&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_acct=C000049198&_version=1&_urlVersion=0&_userid=952835&md5=2983f12e07237d817eccaa75a7c681b4&searchtype=a Link to Supplemental data]
*[http://ecoliwiki.net/tools/chemgen Publicly-available data set]
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!align=left  |Keywords
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phenotype; phenomic profiling; phenotypic signature; hierarchical clustering; responsive genome; high-throughput; chemical genomics; stress; essential; function; antibiotic resistance; synergy

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==Main Points of the Paper ==
*Key Motivation- provide phenotypes for mutants of genes without functional annotation
*Central Goal- systematically evaluate the impact of every gene deletion on ''E.coli'' fitness in diverse environments

*Phenomic Profiling- quantitative description of the response of all single-gene deletions to physiologically relevant stresses and drug challenges
**profiled ~4,000 genes in 324 conditions covering 114 unique stresses (more than half were antimicrobial/antibiotic stress)
**identified thousands of phenotypes 
**identified a diverse set of conditionally essential genes 
***Identified 116 rich-media conditionally essential (CE) genes
**facilitates high-confidence association of genes of unknown function to those of known function
**generates numerous leads concerning drug function

*Hierarchical clustering 
*Phenotypic Signature- response of each mutant strain across all conditions
**high correlation b/t two phenotypic signatures implies a functional connection b/t genes

== Materials and Methods Used ==
===Strain Details===
*Keio single-gene deletion library
*essential gene hypomorphs
*RNA/small protein knockout library
===Equipment and Reagents===
===Procedure===
[[:Category:Phenomic Profiling|Phenomic Profiling]]
===Data Analysis===
Hierarchical clustering

==Phenotype Annotations==
{{AnnotationTableHelp}}
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!|Species!!Taxon ID!!Strain!!Gene (if known)!!OMP!!Phenotype!!Details!!Evidence!!Notes
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Escherichia coli
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K-12 BW25113
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ECK3620-RFAP
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sensitivity to 0.1% bile salts
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Growth
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slow growth
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Growth Curve
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rfaP phosphorylates core heptose of lipopolysaccharide 
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Escherichia coli
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K-12 BW25113
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ECK0223-LPCA
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sensitivity to 1.2 mM DIBUCAINE
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Growth
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slow growth
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Growth Curve
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the target of  DIBUCAINE is the membrane (pmf)
 
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Escherichia coli
|

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K-12 BW25113
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ECK3610-RFAF
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sensitivity to 0.1% bile salts
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Growth
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slow growth
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Growth Curve
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rfaF = ADP-heptose:LPS heptosyltransferase II

target of bile salts: membrane 
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Escherichia coli
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K-12 BW25113
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ECK3042-RFAE
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sensitivity to 30 µg/ml NOVOBIOCIN
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Growth
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slow growth
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Growth Curve
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ECK3042-RFAE = heptose 7-phosphate kinase/heptose 1-phosphate adenyltransferase

the target of NOVOBIOCIN is DNA gyrase
 
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Escherichia coli
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K-12 BW25113
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ECK3610-RFAE
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sensitivity to 0.1% bile salts
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Growth
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slow growth
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Growth Curve
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ECK3042-RFAE = heptose 7-phosphate kinase/heptose 1-phosphate adenyltransferase

target of bile salts: membrane
 

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==Notes==

==References==
{{RefHelp}}
<references/>

[[Category:Phenomic Profiling]]