title: Global functional atlas of Escherichia coli encompassing previously uncharacterized proteins.
abstract: 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.
authors.affiliation: Banting and Best Department of Medical Research, Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Pingzhao
authors.initials: P
authors.lastname: Hu
authors.forename: Sarath Chandra
authors.initials: SC
authors.lastname: Janga
authors.forename: Mohan
authors.initials: M
authors.lastname: Babu
authors.forename: J Javier
authors.initials: JJ
authors.lastname: Díaz-Mejía
authors.forename: Gareth
authors.initials: G
authors.lastname: Butland
authors.forename: Wenhong
authors.initials: W
authors.lastname: Yang
authors.forename: Oxana
authors.initials: O
authors.lastname: Pogoutse
authors.forename: Xinghua
authors.initials: X
authors.lastname: Guo
authors.forename: Sadhna
authors.initials: S
authors.lastname: Phanse
authors.forename: Peter
authors.initials: P
authors.lastname: Wong
authors.forename: Shamanta
authors.initials: S
authors.lastname: Chandran
authors.forename: Constantine
authors.initials: C
authors.lastname: Christopoulos
authors.forename: Anaies
authors.initials: A
authors.lastname: Nazarians-Armavil
authors.forename: Negin Karimi
authors.initials: NK
authors.lastname: Nasseri
authors.forename: Gabriel
authors.initials: G
authors.lastname: Musso
authors.forename: Mehrab
authors.initials: M
authors.lastname: Ali
authors.forename: Nazila
authors.initials: N
authors.lastname: Nazemof
authors.forename: Veronika
authors.initials: V
authors.lastname: Eroukova
authors.forename: Ashkan
authors.initials: A
authors.lastname: Golshani
authors.forename: Alberto
authors.initials: A
authors.lastname: Paccanaro
authors.forename: Jack F
authors.initials: JF
authors.lastname: Greenblatt
authors.forename: Gabriel
authors.initials: G
authors.lastname: Moreno-Hagelsieb
authors.forename: Andrew
authors.initials: A
authors.lastname: Emili
mesh_terms: D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D016680:Genome, Bacterial; D046912:Multiprotein Complexes / Q000235:genetics; D025941:Protein Interaction Mapping / Q000379:methods; D020543:Proteome / Q000235:genetics*
chemical_list: D029968:Escherichia coli Proteins; D046912:Multiprotein Complexes; D020543:Proteome