Quantitative genome-wide genetic interaction screens reveal global epistatic relationships of protein complexes in Escherichia coli.
Identifieur interne : 000954 ( Main/Exploration ); précédent : 000953; suivant : 000955Quantitative genome-wide genetic interaction screens reveal global epistatic relationships of protein complexes in Escherichia coli.
Auteurs : Mohan Babu [Canada] ; Roland Arnold [Canada] ; Cedoljub Bundalovic-Torma [Canada] ; Alla Gagarinova [Canada] ; Keith S. Wong [Canada] ; Ashwani Kumar [Canada] ; Geordie Stewart [Canada] ; Bahram Samanfar [Canada] ; Hiroyuki Aoki [Canada] ; Omar Wagih [Canada] ; James Vlasblom [Canada] ; Sadhna Phanse [Canada] ; Krunal Lad [Canada] ; Angela Yeou Hsiung Yu [Canada] ; Christopher Graham [Canada] ; Ke Jin [Canada] ; Eric Brown [Canada] ; Ashkan Golshani [Canada] ; Philip Kim [Canada] ; Gabriel Moreno-Hagelsieb [Canada] ; Jack Greenblatt [Canada] ; Walid A. Houry [Canada] ; John Parkinson [Canada] ; Andrew Emili [Canada]Source :
- PLoS genetics [ 1553-7404 ] ; 2014.
English descriptors
- KwdEn :
- Cytoplasm (metabolism), Epistasis, Genetic, Escherichia coli (genetics), Genome, Bacterial, Humans, Molecular Chaperones (genetics), Molecular Chaperones (metabolism), Multiprotein Complexes (genetics), Multiprotein Complexes (metabolism), Mutation, Oligonucleotide Array Sequence Analysis, Protein Interaction Maps, Proteomics.
- MESH :
- chemical , genetics : Molecular Chaperones, Multiprotein Complexes.
- genetics : Escherichia coli.
- metabolism : Cytoplasm, Molecular Chaperones, Multiprotein Complexes.
- Epistasis, Genetic, Genome, Bacterial, Humans, Mutation, Oligonucleotide Array Sequence Analysis, Protein Interaction Maps, Proteomics.
Abstract
Large-scale proteomic analyses in Escherichia coli have documented the composition and physical relationships of multiprotein complexes, but not their functional organization into biological pathways and processes. Conversely, genetic interaction (GI) screens can provide insights into the biological role(s) of individual gene and higher order associations. Combining the information from both approaches should elucidate how complexes and pathways intersect functionally at a systems level. However, such integrative analysis has been hindered due to the lack of relevant GI data. Here we present a systematic, unbiased, and quantitative synthetic genetic array screen in E. coli describing the genetic dependencies and functional cross-talk among over 600,000 digenic mutant combinations. Combining this epistasis information with putative functional modules derived from previous proteomic data and genomic context-based methods revealed unexpected associations, including new components required for the biogenesis of iron-sulphur and ribosome integrity, and the interplay between molecular chaperones and proteases. We find that functionally-linked genes co-conserved among γ-proteobacteria are far more likely to have correlated GI profiles than genes with divergent patterns of evolution. Overall, examining bacterial GIs in the context of protein complexes provides avenues for a deeper mechanistic understanding of core microbial systems.
DOI: 10.1371/journal.pgen.1004120
PubMed: 24586182
Affiliations:
- Canada
- Manitoba, Ontario
- Hamilton (Ontario), Saskatchewan, Toronto
- Université McMaster, Université de Regina, Université de Toronto
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Wong</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Kumar, Ashwani" sort="Kumar, Ashwani" uniqKey="Kumar A" first="Ashwani" last="Kumar">Ashwani Kumar</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan</wicri:regionArea><orgName type="university">Université de Regina</orgName><placeName><settlement type="city">Saskatchewan</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Stewart, Geordie" sort="Stewart, Geordie" uniqKey="Stewart G" first="Geordie" last="Stewart">Geordie Stewart</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario</wicri:regionArea><orgName type="university">Université McMaster</orgName><placeName><settlement type="city">Hamilton (Ontario)</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Samanfar, Bahram" sort="Samanfar, Bahram" uniqKey="Samanfar B" first="Bahram" last="Samanfar">Bahram Samanfar</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biology and Ottawa Institute of Systems Biology, Carleton University, Ottawa, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biology and Ottawa Institute of Systems Biology, Carleton University, Ottawa, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Aoki, Hiroyuki" sort="Aoki, Hiroyuki" uniqKey="Aoki H" first="Hiroyuki" last="Aoki">Hiroyuki Aoki</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan</wicri:regionArea><orgName type="university">Université de Regina</orgName><placeName><settlement type="city">Saskatchewan</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Wagih, Omar" sort="Wagih, Omar" uniqKey="Wagih O" first="Omar" last="Wagih">Omar Wagih</name><affiliation wicri:level="4"><nlm:affiliation>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Vlasblom, James" sort="Vlasblom, James" uniqKey="Vlasblom J" first="James" last="Vlasblom">James Vlasblom</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan</wicri:regionArea><orgName type="university">Université de Regina</orgName><placeName><settlement type="city">Saskatchewan</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Phanse, Sadhna" sort="Phanse, Sadhna" uniqKey="Phanse S" first="Sadhna" last="Phanse">Sadhna Phanse</name><affiliation wicri:level="4"><nlm:affiliation>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada ; Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada ; Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Lad, Krunal" sort="Lad, Krunal" uniqKey="Lad K" first="Krunal" last="Lad">Krunal Lad</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan</wicri:regionArea><orgName type="university">Université de Regina</orgName><placeName><settlement type="city">Saskatchewan</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Yeou Hsiung Yu, Angela" sort="Yeou Hsiung Yu, Angela" uniqKey="Yeou Hsiung Yu A" first="Angela" last="Yeou Hsiung Yu">Angela Yeou Hsiung Yu</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Graham, Christopher" sort="Graham, Christopher" uniqKey="Graham C" first="Christopher" last="Graham">Christopher Graham</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan</wicri:regionArea><orgName type="university">Université de Regina</orgName><placeName><settlement type="city">Saskatchewan</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Jin, Ke" sort="Jin, Ke" uniqKey="Jin K" first="Ke" last="Jin">Ke Jin</name><affiliation wicri:level="4"><nlm:affiliation>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada ; Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada ; Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Brown, Eric" sort="Brown, Eric" uniqKey="Brown E" first="Eric" last="Brown">Eric Brown</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario</wicri:regionArea><orgName type="university">Université McMaster</orgName><placeName><settlement type="city">Hamilton (Ontario)</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Golshani, Ashkan" sort="Golshani, Ashkan" uniqKey="Golshani A" first="Ashkan" last="Golshani">Ashkan Golshani</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biology and Ottawa Institute of Systems Biology, Carleton University, Ottawa, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biology and Ottawa Institute of Systems Biology, Carleton University, Ottawa, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Philip" sort="Kim, Philip" uniqKey="Kim P" first="Philip" last="Kim">Philip Kim</name><affiliation wicri:level="4"><nlm:affiliation>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Moreno Hagelsieb, Gabriel" sort="Moreno Hagelsieb, Gabriel" uniqKey="Moreno Hagelsieb G" first="Gabriel" last="Moreno-Hagelsieb">Gabriel Moreno-Hagelsieb</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biology, Wilfrid Laurier University, Waterloo, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biology, Wilfrid Laurier University, Waterloo, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Greenblatt, Jack" sort="Greenblatt, Jack" uniqKey="Greenblatt J" first="Jack" last="Greenblatt">Jack Greenblatt</name><affiliation wicri:level="4"><nlm:affiliation>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada ; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada ; Department of Molecular Genetics, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Houry, Walid A" sort="Houry, Walid A" uniqKey="Houry W" first="Walid A" last="Houry">Walid A. Houry</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Parkinson, John" sort="Parkinson, John" uniqKey="Parkinson J" first="John" last="Parkinson">John Parkinson</name><affiliation wicri:level="4"><nlm:affiliation>Hospital for Sick Children, Toronto, Ontario, Canada ; Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada ; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Hospital for Sick Children, Toronto, Ontario, Canada ; Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada ; Department of Molecular Genetics, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Emili, Andrew" sort="Emili, Andrew" uniqKey="Emili A" first="Andrew" last="Emili">Andrew Emili</name><affiliation wicri:level="4"><nlm:affiliation>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada ; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada ; Department of Molecular Genetics, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:24586182</idno><idno type="pmid">24586182</idno><idno type="doi">10.1371/journal.pgen.1004120</idno><idno type="wicri:Area/PubMed/Corpus">000786</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000786</idno><idno type="wicri:Area/PubMed/Curation">000786</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000786</idno><idno type="wicri:Area/PubMed/Checkpoint">000786</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000786</idno><idno type="wicri:Area/Ncbi/Merge">001695</idno><idno type="wicri:Area/Ncbi/Curation">001695</idno><idno type="wicri:Area/Ncbi/Checkpoint">001695</idno><idno type="wicri:Area/Main/Merge">000956</idno><idno type="wicri:Area/Main/Curation">000954</idno><idno type="wicri:Area/Main/Exploration">000954</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Quantitative genome-wide genetic interaction screens reveal global epistatic relationships of protein complexes in Escherichia coli.</title><author><name sortKey="Babu, Mohan" sort="Babu, Mohan" uniqKey="Babu M" first="Mohan" last="Babu">Mohan Babu</name><affiliation wicri:level="4"><nlm:affiliation>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada ; Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada ; Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Arnold, Roland" sort="Arnold, Roland" uniqKey="Arnold R" first="Roland" last="Arnold">Roland Arnold</name><affiliation wicri:level="4"><nlm:affiliation>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Bundalovic Torma, Cedoljub" sort="Bundalovic Torma, Cedoljub" uniqKey="Bundalovic Torma C" first="Cedoljub" last="Bundalovic-Torma">Cedoljub Bundalovic-Torma</name><affiliation wicri:level="4"><nlm:affiliation>Hospital for Sick Children, Toronto, Ontario, Canada ; Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Hospital for Sick Children, Toronto, Ontario, Canada ; Department of Biochemistry, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Gagarinova, Alla" sort="Gagarinova, Alla" uniqKey="Gagarinova A" first="Alla" last="Gagarinova">Alla Gagarinova</name><affiliation wicri:level="4"><nlm:affiliation>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada ; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada ; Department of Molecular Genetics, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Wong, Keith S" sort="Wong, Keith S" uniqKey="Wong K" first="Keith S" last="Wong">Keith S. Wong</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Kumar, Ashwani" sort="Kumar, Ashwani" uniqKey="Kumar A" first="Ashwani" last="Kumar">Ashwani Kumar</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan</wicri:regionArea><orgName type="university">Université de Regina</orgName><placeName><settlement type="city">Saskatchewan</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Stewart, Geordie" sort="Stewart, Geordie" uniqKey="Stewart G" first="Geordie" last="Stewart">Geordie Stewart</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario</wicri:regionArea><orgName type="university">Université McMaster</orgName><placeName><settlement type="city">Hamilton (Ontario)</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Samanfar, Bahram" sort="Samanfar, Bahram" uniqKey="Samanfar B" first="Bahram" last="Samanfar">Bahram Samanfar</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biology and Ottawa Institute of Systems Biology, Carleton University, Ottawa, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biology and Ottawa Institute of Systems Biology, Carleton University, Ottawa, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Aoki, Hiroyuki" sort="Aoki, Hiroyuki" uniqKey="Aoki H" first="Hiroyuki" last="Aoki">Hiroyuki Aoki</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan</wicri:regionArea><orgName type="university">Université de Regina</orgName><placeName><settlement type="city">Saskatchewan</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Wagih, Omar" sort="Wagih, Omar" uniqKey="Wagih O" first="Omar" last="Wagih">Omar Wagih</name><affiliation wicri:level="4"><nlm:affiliation>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Vlasblom, James" sort="Vlasblom, James" uniqKey="Vlasblom J" first="James" last="Vlasblom">James Vlasblom</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan</wicri:regionArea><orgName type="university">Université de Regina</orgName><placeName><settlement type="city">Saskatchewan</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Phanse, Sadhna" sort="Phanse, Sadhna" uniqKey="Phanse S" first="Sadhna" last="Phanse">Sadhna Phanse</name><affiliation wicri:level="4"><nlm:affiliation>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada ; Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada ; Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Lad, Krunal" sort="Lad, Krunal" uniqKey="Lad K" first="Krunal" last="Lad">Krunal Lad</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan</wicri:regionArea><orgName type="university">Université de Regina</orgName><placeName><settlement type="city">Saskatchewan</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Yeou Hsiung Yu, Angela" sort="Yeou Hsiung Yu, Angela" uniqKey="Yeou Hsiung Yu A" first="Angela" last="Yeou Hsiung Yu">Angela Yeou Hsiung Yu</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Graham, Christopher" sort="Graham, Christopher" uniqKey="Graham C" first="Christopher" last="Graham">Christopher Graham</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan</wicri:regionArea><orgName type="university">Université de Regina</orgName><placeName><settlement type="city">Saskatchewan</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Jin, Ke" sort="Jin, Ke" uniqKey="Jin K" first="Ke" last="Jin">Ke Jin</name><affiliation wicri:level="4"><nlm:affiliation>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada ; Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada ; Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Brown, Eric" sort="Brown, Eric" uniqKey="Brown E" first="Eric" last="Brown">Eric Brown</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario</wicri:regionArea><orgName type="university">Université McMaster</orgName><placeName><settlement type="city">Hamilton (Ontario)</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Golshani, Ashkan" sort="Golshani, Ashkan" uniqKey="Golshani A" first="Ashkan" last="Golshani">Ashkan Golshani</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biology and Ottawa Institute of Systems Biology, Carleton University, Ottawa, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biology and Ottawa Institute of Systems Biology, Carleton University, Ottawa, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Philip" sort="Kim, Philip" uniqKey="Kim P" first="Philip" last="Kim">Philip Kim</name><affiliation wicri:level="4"><nlm:affiliation>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Moreno Hagelsieb, Gabriel" sort="Moreno Hagelsieb, Gabriel" uniqKey="Moreno Hagelsieb G" first="Gabriel" last="Moreno-Hagelsieb">Gabriel Moreno-Hagelsieb</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biology, Wilfrid Laurier University, Waterloo, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biology, Wilfrid Laurier University, Waterloo, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Greenblatt, Jack" sort="Greenblatt, Jack" uniqKey="Greenblatt J" first="Jack" last="Greenblatt">Jack Greenblatt</name><affiliation wicri:level="4"><nlm:affiliation>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada ; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada ; Department of Molecular Genetics, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Houry, Walid A" sort="Houry, Walid A" uniqKey="Houry W" first="Walid A" last="Houry">Walid A. Houry</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Parkinson, John" sort="Parkinson, John" uniqKey="Parkinson J" first="John" last="Parkinson">John Parkinson</name><affiliation wicri:level="4"><nlm:affiliation>Hospital for Sick Children, Toronto, Ontario, Canada ; Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada ; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Hospital for Sick Children, Toronto, Ontario, Canada ; Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada ; Department of Molecular Genetics, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Emili, Andrew" sort="Emili, Andrew" uniqKey="Emili A" first="Andrew" last="Emili">Andrew Emili</name><affiliation wicri:level="4"><nlm:affiliation>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada ; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada ; Department of Molecular Genetics, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author></analytic><series><title level="j">PLoS genetics</title><idno type="eISSN">1553-7404</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Cytoplasm (metabolism)</term><term>Epistasis, Genetic</term><term>Escherichia coli (genetics)</term><term>Genome, Bacterial</term><term>Humans</term><term>Molecular Chaperones (genetics)</term><term>Molecular Chaperones (metabolism)</term><term>Multiprotein Complexes (genetics)</term><term>Multiprotein Complexes (metabolism)</term><term>Mutation</term><term>Oligonucleotide Array Sequence Analysis</term><term>Protein Interaction Maps</term><term>Proteomics</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Molecular Chaperones</term><term>Multiprotein Complexes</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Escherichia coli</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Cytoplasm</term><term>Molecular Chaperones</term><term>Multiprotein Complexes</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Epistasis, Genetic</term><term>Genome, Bacterial</term><term>Humans</term><term>Mutation</term><term>Oligonucleotide Array Sequence Analysis</term><term>Protein Interaction Maps</term><term>Proteomics</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Large-scale proteomic analyses in Escherichia coli have documented the composition and physical relationships of multiprotein complexes, but not their functional organization into biological pathways and processes. Conversely, genetic interaction (GI) screens can provide insights into the biological role(s) of individual gene and higher order associations. Combining the information from both approaches should elucidate how complexes and pathways intersect functionally at a systems level. However, such integrative analysis has been hindered due to the lack of relevant GI data. Here we present a systematic, unbiased, and quantitative synthetic genetic array screen in E. coli describing the genetic dependencies and functional cross-talk among over 600,000 digenic mutant combinations. Combining this epistasis information with putative functional modules derived from previous proteomic data and genomic context-based methods revealed unexpected associations, including new components required for the biogenesis of iron-sulphur and ribosome integrity, and the interplay between molecular chaperones and proteases. We find that functionally-linked genes co-conserved among γ-proteobacteria are far more likely to have correlated GI profiles than genes with divergent patterns of evolution. Overall, examining bacterial GIs in the context of protein complexes provides avenues for a deeper mechanistic understanding of core microbial systems.</div></front></TEI><affiliations><list><country><li>Canada</li></country><region><li>Manitoba</li><li>Ontario</li></region><settlement><li>Hamilton (Ontario)</li><li>Saskatchewan</li><li>Toronto</li></settlement><orgName><li>Université McMaster</li><li>Université de Regina</li><li>Université de Toronto</li></orgName></list><tree><country name="Canada"><region name="Ontario"><name sortKey="Babu, Mohan" sort="Babu, Mohan" uniqKey="Babu M" first="Mohan" last="Babu">Mohan Babu</name></region><name sortKey="Aoki, Hiroyuki" sort="Aoki, Hiroyuki" uniqKey="Aoki H" first="Hiroyuki" last="Aoki">Hiroyuki Aoki</name><name sortKey="Arnold, Roland" sort="Arnold, Roland" uniqKey="Arnold R" first="Roland" last="Arnold">Roland Arnold</name><name sortKey="Brown, Eric" sort="Brown, Eric" uniqKey="Brown E" first="Eric" last="Brown">Eric Brown</name><name sortKey="Bundalovic Torma, Cedoljub" sort="Bundalovic Torma, Cedoljub" uniqKey="Bundalovic Torma C" first="Cedoljub" last="Bundalovic-Torma">Cedoljub Bundalovic-Torma</name><name sortKey="Emili, Andrew" sort="Emili, Andrew" uniqKey="Emili A" first="Andrew" last="Emili">Andrew Emili</name><name sortKey="Gagarinova, Alla" sort="Gagarinova, Alla" uniqKey="Gagarinova A" first="Alla" last="Gagarinova">Alla Gagarinova</name><name sortKey="Golshani, Ashkan" sort="Golshani, Ashkan" uniqKey="Golshani A" first="Ashkan" last="Golshani">Ashkan Golshani</name><name sortKey="Graham, Christopher" sort="Graham, Christopher" uniqKey="Graham C" first="Christopher" last="Graham">Christopher Graham</name><name sortKey="Greenblatt, Jack" sort="Greenblatt, Jack" uniqKey="Greenblatt J" first="Jack" last="Greenblatt">Jack Greenblatt</name><name sortKey="Houry, Walid A" sort="Houry, Walid A" uniqKey="Houry W" first="Walid A" last="Houry">Walid A. Houry</name><name sortKey="Jin, Ke" sort="Jin, Ke" uniqKey="Jin K" first="Ke" last="Jin">Ke Jin</name><name sortKey="Kim, Philip" sort="Kim, Philip" uniqKey="Kim P" first="Philip" last="Kim">Philip Kim</name><name sortKey="Kumar, Ashwani" sort="Kumar, Ashwani" uniqKey="Kumar A" first="Ashwani" last="Kumar">Ashwani Kumar</name><name sortKey="Lad, Krunal" sort="Lad, Krunal" uniqKey="Lad K" first="Krunal" last="Lad">Krunal Lad</name><name sortKey="Moreno Hagelsieb, Gabriel" sort="Moreno Hagelsieb, Gabriel" uniqKey="Moreno Hagelsieb G" first="Gabriel" last="Moreno-Hagelsieb">Gabriel Moreno-Hagelsieb</name><name sortKey="Parkinson, John" sort="Parkinson, John" uniqKey="Parkinson J" first="John" last="Parkinson">John Parkinson</name><name sortKey="Phanse, Sadhna" sort="Phanse, Sadhna" uniqKey="Phanse S" first="Sadhna" last="Phanse">Sadhna Phanse</name><name sortKey="Samanfar, Bahram" sort="Samanfar, Bahram" uniqKey="Samanfar B" first="Bahram" last="Samanfar">Bahram Samanfar</name><name sortKey="Stewart, Geordie" sort="Stewart, Geordie" uniqKey="Stewart G" first="Geordie" last="Stewart">Geordie Stewart</name><name sortKey="Vlasblom, James" sort="Vlasblom, James" uniqKey="Vlasblom J" first="James" last="Vlasblom">James Vlasblom</name><name sortKey="Wagih, Omar" sort="Wagih, Omar" uniqKey="Wagih O" first="Omar" last="Wagih">Omar Wagih</name><name sortKey="Wong, Keith S" sort="Wong, Keith S" uniqKey="Wong K" first="Keith S" last="Wong">Keith S. Wong</name><name sortKey="Yeou Hsiung Yu, Angela" sort="Yeou Hsiung Yu, Angela" uniqKey="Yeou Hsiung Yu A" first="Angela" last="Yeou Hsiung Yu">Angela Yeou Hsiung Yu</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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