title: Usefulness and limitations of dK random graph models to predict interactions and functional homogeneity in biological networks under a pseudo-likelihood parameter estimation approach.
abstract: BACKGROUND
  Many aspects of biological functions can be modeled by biological networks, such as protein interaction networks, metabolic networks, and gene coexpression networks. Studying the statistical properties of these networks in turn allows us to infer biological function. Complex statistical network models can potentially more accurately describe the networks, but it is not clear whether such complex models are better suited to find biologically meaningful subnetworks.
  
  
  RESULTS
  Recent studies have shown that the degree distribution of the nodes is not an adequate statistic in many molecular networks. We sought to extend this statistic with 2nd and 3rd order degree correlations and developed a pseudo-likelihood approach to estimate the parameters. The approach was used to analyze the MIPS and BIOGRID yeast protein interaction networks, and two yeast coexpression networks. We showed that 2nd order degree correlation information gave better predictions of gene interactions in both protein interaction and gene coexpression networks. However, in the biologically important task of predicting functionally homogeneous modules, degree correlation information performs marginally better in the case of the MIPS and BIOGRID protein interaction networks, but worse in the case of gene coexpression networks.
  
  
  CONCLUSIONS
  Our use of dK models showed that incorporation of degree correlations could increase predictive power in some contexts, albeit sometimes marginally, but, in all contexts, the use of third-order degree correlations decreased accuracy. However, it is possible that other parameter estimation methods, such as maximum likelihood, will show the usefulness of incorporating 2nd and 3rd degree correlations in predicting functionally homogeneous modules.
authors.affiliation: School of Mathematics, Shandong University, Jinan, Shandong 250100, PR China. wwhlazio@mail.sdu.edu.cn
authors.forename: Wenhui
authors.initials: W
authors.lastname: Wang
authors.forename: Juan
authors.initials: J
authors.lastname: Nunez-Iglesias
authors.forename: Yihui
authors.initials: Y
authors.lastname: Luan
authors.forename: Fengzhu
authors.initials: F
authors.lastname: Sun
mesh_terms: D019295:Computational Biology / Q000379:methods*; D053263:Gene Regulatory Networks; D015233:Models, Statistical; D025941:Protein Interaction Mapping / Q000379:methods