title: Integrating multiple protein-protein interaction networks to prioritize disease genes: a Bayesian regression approach.
abstract: BACKGROUND
  The identification of genes responsible for human inherited diseases is one of the most challenging tasks in human genetics. Recent studies based on phenotype similarity and gene proximity have demonstrated great success in prioritizing candidate genes for human diseases. However, most of these methods rely on a single protein-protein interaction (PPI) network to calculate similarities between genes, and thus greatly restrict the scope of application of such methods. Meanwhile, independently constructed and maintained PPI networks are usually quite diverse in coverage and quality, making the selection of a suitable PPI network inevitable but difficult.
  
  
  METHODS
  We adopt a linear model to explain similarities between disease phenotypes using gene proximities that are quantified by diffusion kernels of one or more PPI networks. We solve this model via a Bayesian approach, and we derive an analytic form for Bayes factor that naturally measures the strength of association between a query disease and a candidate gene and thus can be used as a score to prioritize candidate genes. This method is intrinsically capable of integrating multiple PPI networks.
  
  
  RESULTS
  We show that gene proximities calculated from PPI networks imply phenotype similarities. We demonstrate the effectiveness of the Bayesian regression approach on five PPI networks via large scale leave-one-out cross-validation experiments and summarize the results in terms of the mean rank ratio of known disease genes and the area under the receiver operating characteristic curve (AUC). We further show the capability of our approach in integrating multiple PPI networks.
  
  
  CONCLUSIONS
  The Bayesian regression approach can achieve much higher performance than the existing CIPHER approach and the ordinary linear regression method. The integration of multiple PPI networks can greatly improve the scope of application of the proposed method in the inference of disease genes.
authors.affiliation: MOE Key Laboratory of Bioinformatics and Bioinformatics Division, TNLIST/Department of Automation, Tsinghua University, Beijing 10084, China.
authors.forename: Wangshu
authors.initials: W
authors.lastname: Zhang
authors.forename: Fengzhu
authors.initials: F
authors.lastname: Sun
authors.forename: Rui
authors.initials: R
authors.lastname: Jiang
mesh_terms: D001499:Bayes Theorem; D019295:Computational Biology / Q000379:methods; D006801:Humans; D016014:Linear Models; D010641:Phenotype; D025941:Protein Interaction Mapping / Q000379:methods*; D011506:Proteins / Q000032:analysis
chemical_list: D011506:Proteins