Quantitative genome-wide genetic interaction screens reveal global epistatic relationships of protein complexes in Escherichia coli.
Identifieur interne : 000786 ( PubMed/Corpus ); précédent : 000785; suivant : 000787Quantitative genome-wide genetic interaction screens reveal global epistatic relationships of protein complexes in Escherichia coli.
Auteurs : Mohan Babu ; Roland Arnold ; Cedoljub Bundalovic-Torma ; Alla Gagarinova ; Keith S. Wong ; Ashwani Kumar ; Geordie Stewart ; Bahram Samanfar ; Hiroyuki Aoki ; Omar Wagih ; James Vlasblom ; Sadhna Phanse ; Krunal Lad ; Angela Yeou Hsiung Yu ; Christopher Graham ; Ke Jin ; Eric Brown ; Ashkan Golshani ; Philip Kim ; Gabriel Moreno-Hagelsieb ; Jack Greenblatt ; Walid A. Houry ; John Parkinson ; Andrew EmiliSource :
- 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
Links to Exploration step
pubmed:24586182Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><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><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></affiliation></author><author><name sortKey="Arnold, Roland" sort="Arnold, Roland" uniqKey="Arnold R" first="Roland" last="Arnold">Roland Arnold</name><affiliation><nlm:affiliation>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation></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><nlm:affiliation>Hospital for Sick Children, Toronto, Ontario, Canada ; Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Gagarinova, Alla" sort="Gagarinova, Alla" uniqKey="Gagarinova A" first="Alla" last="Gagarinova">Alla Gagarinova</name><affiliation><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></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><nlm:affiliation>Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Kumar, Ashwani" sort="Kumar, Ashwani" uniqKey="Kumar A" first="Ashwani" last="Kumar">Ashwani Kumar</name><affiliation><nlm:affiliation>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Stewart, Geordie" sort="Stewart, Geordie" uniqKey="Stewart G" first="Geordie" last="Stewart">Geordie Stewart</name><affiliation><nlm:affiliation>Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Samanfar, Bahram" sort="Samanfar, Bahram" uniqKey="Samanfar B" first="Bahram" last="Samanfar">Bahram Samanfar</name><affiliation><nlm:affiliation>Department of Biology and Ottawa Institute of Systems Biology, Carleton University, Ottawa, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Aoki, Hiroyuki" sort="Aoki, Hiroyuki" uniqKey="Aoki H" first="Hiroyuki" last="Aoki">Hiroyuki Aoki</name><affiliation><nlm:affiliation>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Wagih, Omar" sort="Wagih, Omar" uniqKey="Wagih O" first="Omar" last="Wagih">Omar Wagih</name><affiliation><nlm:affiliation>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Vlasblom, James" sort="Vlasblom, James" uniqKey="Vlasblom J" first="James" last="Vlasblom">James Vlasblom</name><affiliation><nlm:affiliation>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Phanse, Sadhna" sort="Phanse, Sadhna" uniqKey="Phanse S" first="Sadhna" last="Phanse">Sadhna Phanse</name><affiliation><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></affiliation></author><author><name sortKey="Lad, Krunal" sort="Lad, Krunal" uniqKey="Lad K" first="Krunal" last="Lad">Krunal Lad</name><affiliation><nlm:affiliation>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</nlm:affiliation></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><nlm:affiliation>Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Graham, Christopher" sort="Graham, Christopher" uniqKey="Graham C" first="Christopher" last="Graham">Christopher Graham</name><affiliation><nlm:affiliation>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Jin, Ke" sort="Jin, Ke" uniqKey="Jin K" first="Ke" last="Jin">Ke Jin</name><affiliation><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></affiliation></author><author><name sortKey="Brown, Eric" sort="Brown, Eric" uniqKey="Brown E" first="Eric" last="Brown">Eric Brown</name><affiliation><nlm:affiliation>Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Golshani, Ashkan" sort="Golshani, Ashkan" uniqKey="Golshani A" first="Ashkan" last="Golshani">Ashkan Golshani</name><affiliation><nlm:affiliation>Department of Biology and Ottawa Institute of Systems Biology, Carleton University, Ottawa, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Kim, Philip" sort="Kim, Philip" uniqKey="Kim P" first="Philip" last="Kim">Philip Kim</name><affiliation><nlm:affiliation>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation></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><nlm:affiliation>Department of Biology, Wilfrid Laurier University, Waterloo, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Greenblatt, Jack" sort="Greenblatt, Jack" uniqKey="Greenblatt J" first="Jack" last="Greenblatt">Jack Greenblatt</name><affiliation><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></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><nlm:affiliation>Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Parkinson, John" sort="Parkinson, John" uniqKey="Parkinson J" first="John" last="Parkinson">John Parkinson</name><affiliation><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></affiliation></author><author><name sortKey="Emili, Andrew" sort="Emili, Andrew" uniqKey="Emili A" first="Andrew" last="Emili">Andrew Emili</name><affiliation><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></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></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><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></affiliation></author><author><name sortKey="Arnold, Roland" sort="Arnold, Roland" uniqKey="Arnold R" first="Roland" last="Arnold">Roland Arnold</name><affiliation><nlm:affiliation>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation></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><nlm:affiliation>Hospital for Sick Children, Toronto, Ontario, Canada ; Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Gagarinova, Alla" sort="Gagarinova, Alla" uniqKey="Gagarinova A" first="Alla" last="Gagarinova">Alla Gagarinova</name><affiliation><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></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><nlm:affiliation>Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Kumar, Ashwani" sort="Kumar, Ashwani" uniqKey="Kumar A" first="Ashwani" last="Kumar">Ashwani Kumar</name><affiliation><nlm:affiliation>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Stewart, Geordie" sort="Stewart, Geordie" uniqKey="Stewart G" first="Geordie" last="Stewart">Geordie Stewart</name><affiliation><nlm:affiliation>Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Samanfar, Bahram" sort="Samanfar, Bahram" uniqKey="Samanfar B" first="Bahram" last="Samanfar">Bahram Samanfar</name><affiliation><nlm:affiliation>Department of Biology and Ottawa Institute of Systems Biology, Carleton University, Ottawa, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Aoki, Hiroyuki" sort="Aoki, Hiroyuki" uniqKey="Aoki H" first="Hiroyuki" last="Aoki">Hiroyuki Aoki</name><affiliation><nlm:affiliation>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Wagih, Omar" sort="Wagih, Omar" uniqKey="Wagih O" first="Omar" last="Wagih">Omar Wagih</name><affiliation><nlm:affiliation>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Vlasblom, James" sort="Vlasblom, James" uniqKey="Vlasblom J" first="James" last="Vlasblom">James Vlasblom</name><affiliation><nlm:affiliation>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Phanse, Sadhna" sort="Phanse, Sadhna" uniqKey="Phanse S" first="Sadhna" last="Phanse">Sadhna Phanse</name><affiliation><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></affiliation></author><author><name sortKey="Lad, Krunal" sort="Lad, Krunal" uniqKey="Lad K" first="Krunal" last="Lad">Krunal Lad</name><affiliation><nlm:affiliation>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</nlm:affiliation></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><nlm:affiliation>Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Graham, Christopher" sort="Graham, Christopher" uniqKey="Graham C" first="Christopher" last="Graham">Christopher Graham</name><affiliation><nlm:affiliation>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Jin, Ke" sort="Jin, Ke" uniqKey="Jin K" first="Ke" last="Jin">Ke Jin</name><affiliation><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></affiliation></author><author><name sortKey="Brown, Eric" sort="Brown, Eric" uniqKey="Brown E" first="Eric" last="Brown">Eric Brown</name><affiliation><nlm:affiliation>Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Golshani, Ashkan" sort="Golshani, Ashkan" uniqKey="Golshani A" first="Ashkan" last="Golshani">Ashkan Golshani</name><affiliation><nlm:affiliation>Department of Biology and Ottawa Institute of Systems Biology, Carleton University, Ottawa, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Kim, Philip" sort="Kim, Philip" uniqKey="Kim P" first="Philip" last="Kim">Philip Kim</name><affiliation><nlm:affiliation>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation></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><nlm:affiliation>Department of Biology, Wilfrid Laurier University, Waterloo, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Greenblatt, Jack" sort="Greenblatt, Jack" uniqKey="Greenblatt J" first="Jack" last="Greenblatt">Jack Greenblatt</name><affiliation><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></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><nlm:affiliation>Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Parkinson, John" sort="Parkinson, John" uniqKey="Parkinson J" first="John" last="Parkinson">John Parkinson</name><affiliation><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></affiliation></author><author><name sortKey="Emili, Andrew" sort="Emili, Andrew" uniqKey="Emili A" first="Andrew" last="Emili">Andrew Emili</name><affiliation><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></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><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">24586182</PMID><DateCreated><Year>2014</Year><Month>03</Month><Day>03</Day></DateCreated><DateCompleted><Year>2014</Year><Month>12</Month><Day>15</Day></DateCompleted><DateRevised><Year>2016</Year><Month>10</Month><Day>19</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">1553-7404</ISSN><JournalIssue CitedMedium="Internet"><Volume>10</Volume><Issue>2</Issue><PubDate><Year>2014</Year><Month>Feb</Month></PubDate></JournalIssue><Title>PLoS genetics</Title><ISOAbbreviation>PLoS Genet.</ISOAbbreviation></Journal><ArticleTitle>Quantitative genome-wide genetic interaction screens reveal global epistatic relationships of protein complexes in Escherichia coli.</ArticleTitle><Pagination><MedlinePgn>e1004120</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1371/journal.pgen.1004120</ELocationID><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Babu</LastName><ForeName>Mohan</ForeName><Initials>M</Initials><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Arnold</LastName><ForeName>Roland</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bundalovic-Torma</LastName><ForeName>Cedoljub</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Hospital for Sick Children, Toronto, Ontario, Canada ; Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gagarinova</LastName><ForeName>Alla</ForeName><Initials>A</Initials><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wong</LastName><ForeName>Keith S</ForeName><Initials>KS</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kumar</LastName><ForeName>Ashwani</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Stewart</LastName><ForeName>Geordie</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Samanfar</LastName><ForeName>Bahram</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Department of Biology and Ottawa Institute of Systems Biology, Carleton University, Ottawa, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Aoki</LastName><ForeName>Hiroyuki</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wagih</LastName><ForeName>Omar</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vlasblom</LastName><ForeName>James</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Phanse</LastName><ForeName>Sadhna</ForeName><Initials>S</Initials><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lad</LastName><ForeName>Krunal</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yeou Hsiung Yu</LastName><ForeName>Angela</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Graham</LastName><ForeName>Christopher</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jin</LastName><ForeName>Ke</ForeName><Initials>K</Initials><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Brown</LastName><ForeName>Eric</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Golshani</LastName><ForeName>Ashkan</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Biology and Ottawa Institute of Systems Biology, Carleton University, Ottawa, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kim</LastName><ForeName>Philip</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Banting and Best Department of Medical Research, Donnelly Centre, University of 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