Global functional atlas of Escherichia coli encompassing previously uncharacterized proteins.

One-third of the 4,225 protein-coding genes of Escherichia coli K-12 remain functionally unannotated (orphans). Many map to distant clades such as Archaea, suggesting involvement in basic prokaryotic traits, whereas others appear restricted to E. coli, including pathogenic strains. To elucidate the...

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Main Authors: Pingzhao Hu, Sarath Chandra Janga, Mohan Babu, J Javier Díaz-Mejía, Gareth Butland, Wenhong Yang, Oxana Pogoutse, Xinghua Guo, Sadhna Phanse, Peter Wong, Shamanta Chandran, Constantine Christopoulos, Anaies Nazarians-Armavil, Negin Karimi Nasseri, Gabriel Musso, Mehrab Ali, Nazila Nazemof, Veronika Eroukova, Ashkan Golshani, Alberto Paccanaro, Jack F Greenblatt, Gabriel Moreno-Hagelsieb, Andrew Emili
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2009-04-01
Series:PLoS Biology
Online Access:https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.1000096&type=printable
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author Pingzhao Hu
Sarath Chandra Janga
Mohan Babu
J Javier Díaz-Mejía
Gareth Butland
Wenhong Yang
Oxana Pogoutse
Xinghua Guo
Sadhna Phanse
Peter Wong
Shamanta Chandran
Constantine Christopoulos
Anaies Nazarians-Armavil
Negin Karimi Nasseri
Gabriel Musso
Mehrab Ali
Nazila Nazemof
Veronika Eroukova
Ashkan Golshani
Alberto Paccanaro
Jack F Greenblatt
Gabriel Moreno-Hagelsieb
Andrew Emili
author_facet Pingzhao Hu
Sarath Chandra Janga
Mohan Babu
J Javier Díaz-Mejía
Gareth Butland
Wenhong Yang
Oxana Pogoutse
Xinghua Guo
Sadhna Phanse
Peter Wong
Shamanta Chandran
Constantine Christopoulos
Anaies Nazarians-Armavil
Negin Karimi Nasseri
Gabriel Musso
Mehrab Ali
Nazila Nazemof
Veronika Eroukova
Ashkan Golshani
Alberto Paccanaro
Jack F Greenblatt
Gabriel Moreno-Hagelsieb
Andrew Emili
author_sort Pingzhao Hu
collection DOAJ
description One-third of the 4,225 protein-coding genes of Escherichia coli K-12 remain functionally unannotated (orphans). Many map to distant clades such as Archaea, suggesting involvement in basic prokaryotic traits, whereas others appear restricted to E. coli, including pathogenic strains. To elucidate the orphans' biological roles, we performed an extensive proteomic survey using affinity-tagged E. coli strains and generated comprehensive genomic context inferences to derive a high-confidence compendium for virtually the entire proteome consisting of 5,993 putative physical interactions and 74,776 putative functional associations, most of which are novel. Clustering of the respective probabilistic networks revealed putative orphan membership in discrete multiprotein complexes and functional modules together with annotated gene products, whereas a machine-learning strategy based on network integration implicated the orphans in specific biological processes. We provide additional experimental evidence supporting orphan participation in protein synthesis, amino acid metabolism, biofilm formation, motility, and assembly of the bacterial cell envelope. This resource provides a "systems-wide" functional blueprint of a model microbe, with insights into the biological and evolutionary significance of previously uncharacterized proteins.
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spelling doaj-art-512d2be209f844b598c2040abfcbe06f2025-08-20T02:00:48ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852009-04-0174e9610.1371/journal.pbio.1000096Global functional atlas of Escherichia coli encompassing previously uncharacterized proteins.Pingzhao HuSarath Chandra JangaMohan BabuJ Javier Díaz-MejíaGareth ButlandWenhong YangOxana PogoutseXinghua GuoSadhna PhansePeter WongShamanta ChandranConstantine ChristopoulosAnaies Nazarians-ArmavilNegin Karimi NasseriGabriel MussoMehrab AliNazila NazemofVeronika EroukovaAshkan GolshaniAlberto PaccanaroJack F GreenblattGabriel Moreno-HagelsiebAndrew EmiliOne-third of the 4,225 protein-coding genes of Escherichia coli K-12 remain functionally unannotated (orphans). Many map to distant clades such as Archaea, suggesting involvement in basic prokaryotic traits, whereas others appear restricted to E. coli, including pathogenic strains. To elucidate the orphans' biological roles, we performed an extensive proteomic survey using affinity-tagged E. coli strains and generated comprehensive genomic context inferences to derive a high-confidence compendium for virtually the entire proteome consisting of 5,993 putative physical interactions and 74,776 putative functional associations, most of which are novel. Clustering of the respective probabilistic networks revealed putative orphan membership in discrete multiprotein complexes and functional modules together with annotated gene products, whereas a machine-learning strategy based on network integration implicated the orphans in specific biological processes. We provide additional experimental evidence supporting orphan participation in protein synthesis, amino acid metabolism, biofilm formation, motility, and assembly of the bacterial cell envelope. This resource provides a "systems-wide" functional blueprint of a model microbe, with insights into the biological and evolutionary significance of previously uncharacterized proteins.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.1000096&type=printable
spellingShingle Pingzhao Hu
Sarath Chandra Janga
Mohan Babu
J Javier Díaz-Mejía
Gareth Butland
Wenhong Yang
Oxana Pogoutse
Xinghua Guo
Sadhna Phanse
Peter Wong
Shamanta Chandran
Constantine Christopoulos
Anaies Nazarians-Armavil
Negin Karimi Nasseri
Gabriel Musso
Mehrab Ali
Nazila Nazemof
Veronika Eroukova
Ashkan Golshani
Alberto Paccanaro
Jack F Greenblatt
Gabriel Moreno-Hagelsieb
Andrew Emili
Global functional atlas of Escherichia coli encompassing previously uncharacterized proteins.
PLoS Biology
title Global functional atlas of Escherichia coli encompassing previously uncharacterized proteins.
title_full Global functional atlas of Escherichia coli encompassing previously uncharacterized proteins.
title_fullStr Global functional atlas of Escherichia coli encompassing previously uncharacterized proteins.
title_full_unstemmed Global functional atlas of Escherichia coli encompassing previously uncharacterized proteins.
title_short Global functional atlas of Escherichia coli encompassing previously uncharacterized proteins.
title_sort global functional atlas of escherichia coli encompassing previously uncharacterized proteins
url https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.1000096&type=printable
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