Global Functional Atlas of Escherichia coli Encompassing Previously Uncharacterized Proteins

By P. Hu, S. Janga, M. Babu, J. J. Díaz-Mejía, G. Butland, Wenhong Yang, O. Pogoutse, Xinghua Guo, S. Phanse, Peter Wong and 13 more. 2009

402 citations recorded by the source corpus.

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.

Subfields: Molecular Biology

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Citations in the corpus

Phenotypic Landscape of a Bacterial Cell (2010, neutral): “coli (Hu et al., 2009), we find that the fraction of mutant orphan genes A B”
Extensive complementarity between gene function prediction methods (2016, background): “…the individual networks resulted in gene modules that were more functionally consistent (Lee et al., 2004; von Mering et al., 2005) and could thus more accurately predict gene function (Troyanskaya et al., 2003; Hu et al., 2009) or phenotypic effects of gene perturbation (Lee et al., 2010).”
Estimation of Simultaneously Sparse and Low Rank Matrices (2012, methodology): “We use data from (Hu et al., 2009), in which protein interactions in Escherichia coli bacteria are scored by strength in [0, 2].”
Protein Complexes in Bacteria (2015, methodology): “coli [5] are compared to complexes ofM.”
A Census of Human Soluble Protein Complexes (2012, neutral): “…identification of protein complexes in model organisms (Butland et al., 2005; Gavin et al., 2002, 2006; Guruharsha et al., 2011; Ho et al., 2002; Hu et al., 2009; Krogan et al., 2006; Kühner et al., 2009), clone-based protein purification techniques remain challenging for proteome-scale…”
A Protein Complex Network of Drosophila melanogaster (2011, methodology): “, 2006), Escherichia coli (Hu et al., 2009), and Mycoplasma pneumoniae (Kühner et al.”
Interactome3D: adding structural details to protein networks (2013, background): “These IMEx and MIMIx entries may include, in some cases, interactions identified in larger complexes for which additional experimental or computational validation has been done (and reported in the original publication) to infer the binary nature of the interaction 56 .”