title: The topology of the bacterial co-conserved protein network and its implications for predicting protein function.
abstract: BACKGROUND
  Protein-protein interactions networks are most often generated from physical protein-protein interaction data. Co-conservation, also known as phylogenetic profiles, is an alternative source of information for generating protein interaction networks. Co-conservation methods generate interaction networks among proteins that are gained or lost together through evolution. Co-conservation is a particularly useful technique in the compact bacteria genomes. Prior studies in yeast suggest that the topology of protein-protein interaction networks generated from physical interaction assays can offer important insight into protein function. Here, we hypothesize that in bacteria, the topology of protein interaction networks derived via co-conservation information could similarly improve methods for predicting protein function. Since the topology of bacteria co-conservation protein-protein interaction networks has not previously been studied in depth, we first perform such an analysis for co-conservation networks in E. coli K12. Next, we demonstrate one way in which network connectivity measures and global and local function distribution can be exploited to predict protein function for previously uncharacterized proteins.
  
  
  RESULTS
  Our results showed, like most biological networks, our bacteria co-conserved protein-protein interaction networks had scale-free topologies. Our results indicated that some properties of the physical yeast interaction network hold in our bacteria co-conservation networks, such as high connectivity for essential proteins. However, the high connectivity among protein complexes in the yeast physical network was not seen in the co-conservation network which uses all bacteria as the reference set. We found that the distribution of node connectivity varied by functional category and could be informative for function prediction. By integrating of functional information from different annotation sources and using the network topology, we were able to infer function for uncharacterized proteins.
  
  
  CONCLUSIONS
  Interactions networks based on co-conservation can contain information distinct from networks based on physical or other interaction types. Our study has shown co-conservation based networks to exhibit a scale free topology, as expected for biological networks. We also revealed ways that connectivity in our networks can be informative for the functional characterization of proteins.
authors.affiliation: Center for Computational Pharmacology, University of Colorado School of Medicine, Aurora, Colorado 80045, USA. anis.karimpour-fard@uchsc.edu
authors.forename: Anis
authors.initials: A
authors.lastname: Karimpour-Fard
authors.forename: Sonia M
authors.initials: SM
authors.lastname: Leach
authors.forename: Lawrence E
authors.initials: LE
authors.lastname: Hunter
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Gill
mesh_terms: D000465:Algorithms; D016000:Cluster Analysis; D048168:Escherichia coli K12 / Q000235:genetics; D016680:Genome, Bacterial; D053858:Metabolic Networks and Pathways; D010802:Phylogeny; D011237:Predictive Value of Tests; D025941:Protein Interaction Mapping / Q000379:methods*; D012016:Reference Values; D015203:Reproducibility of Results