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Quantitative Genome-Wide Genetic Interaction Screens Reveal Global Epistatic Relationships of Protein Complexes in Escherichia coli
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930520/ https://www.ncbi.nlm.nih.gov/pubmed/24586182 http://dx.doi.org/10.1371/journal.pgen.1004120 |
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author | Babu, Mohan Arnold, Roland Bundalovic-Torma, Cedoljub Gagarinova, Alla Wong, Keith S. Kumar, Ashwani Stewart, Geordie Samanfar, Bahram Aoki, Hiroyuki Wagih, Omar Vlasblom, James Phanse, Sadhna Lad, Krunal Yeou Hsiung Yu, Angela Graham, Christopher Jin, Ke Brown, Eric Golshani, Ashkan Kim, Philip Moreno-Hagelsieb, Gabriel Greenblatt, Jack Houry, Walid A. Parkinson, John Emili, Andrew |
author_facet | Babu, Mohan Arnold, Roland Bundalovic-Torma, Cedoljub Gagarinova, Alla Wong, Keith S. Kumar, Ashwani Stewart, Geordie Samanfar, Bahram Aoki, Hiroyuki Wagih, Omar Vlasblom, James Phanse, Sadhna Lad, Krunal Yeou Hsiung Yu, Angela Graham, Christopher Jin, Ke Brown, Eric Golshani, Ashkan Kim, Philip Moreno-Hagelsieb, Gabriel Greenblatt, Jack Houry, Walid A. Parkinson, John Emili, Andrew |
author_sort | Babu, Mohan |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3930520 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39305202014-02-25 Quantitative Genome-Wide Genetic Interaction Screens Reveal Global Epistatic Relationships of Protein Complexes in Escherichia coli Babu, Mohan Arnold, Roland Bundalovic-Torma, Cedoljub Gagarinova, Alla Wong, Keith S. Kumar, Ashwani Stewart, Geordie Samanfar, Bahram Aoki, Hiroyuki Wagih, Omar Vlasblom, James Phanse, Sadhna Lad, Krunal Yeou Hsiung Yu, Angela Graham, Christopher Jin, Ke Brown, Eric Golshani, Ashkan Kim, Philip Moreno-Hagelsieb, Gabriel Greenblatt, Jack Houry, Walid A. Parkinson, John Emili, Andrew PLoS Genet Research Article 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. Public Library of Science 2014-02-20 /pmc/articles/PMC3930520/ /pubmed/24586182 http://dx.doi.org/10.1371/journal.pgen.1004120 Text en © 2014 Babu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Babu, Mohan Arnold, Roland Bundalovic-Torma, Cedoljub Gagarinova, Alla Wong, Keith S. Kumar, Ashwani Stewart, Geordie Samanfar, Bahram Aoki, Hiroyuki Wagih, Omar Vlasblom, James Phanse, Sadhna Lad, Krunal Yeou Hsiung Yu, Angela Graham, Christopher Jin, Ke Brown, Eric Golshani, Ashkan Kim, Philip Moreno-Hagelsieb, Gabriel Greenblatt, Jack Houry, Walid A. Parkinson, John Emili, Andrew Quantitative Genome-Wide Genetic Interaction Screens Reveal Global Epistatic Relationships of Protein Complexes in Escherichia coli |
title | Quantitative Genome-Wide Genetic Interaction Screens Reveal Global Epistatic Relationships of Protein Complexes in Escherichia coli
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title_full | Quantitative Genome-Wide Genetic Interaction Screens Reveal Global Epistatic Relationships of Protein Complexes in Escherichia coli
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title_fullStr | Quantitative Genome-Wide Genetic Interaction Screens Reveal Global Epistatic Relationships of Protein Complexes in Escherichia coli
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title_full_unstemmed | Quantitative Genome-Wide Genetic Interaction Screens Reveal Global Epistatic Relationships of Protein Complexes in Escherichia coli
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title_short | Quantitative Genome-Wide Genetic Interaction Screens Reveal Global Epistatic Relationships of Protein Complexes in Escherichia coli
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title_sort | quantitative genome-wide genetic interaction screens reveal global epistatic relationships of protein complexes in escherichia coli |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930520/ https://www.ncbi.nlm.nih.gov/pubmed/24586182 http://dx.doi.org/10.1371/journal.pgen.1004120 |
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