MSIGNET: a Metropolis sampling-based method for global optimal significant network identification

In this paper, we propose a novel approach namely MSIGNET to identify subnetworks with significantly expressed genes by integrating context specific gene expression and protein-protein interaction (PPI) data. Specifically, we integrate differential expression of each gene and mutual information of gene pairs in a Bayesian framework and use Metropolis sampling to identify functional interactions. During the sampling process, a conditional probability is calculated given a randomly selected gene to control the network state transition. Our method provides global statistics of all genes and their interactions, and finally achieves a global optimal sub-network. We apply MSIGNET to simulated data and have demonstrated its superior performance over comparable network identification tools. Using a validated Parkinson data set we show that the network identified using MSIGNET is consistent to previously reported results but provides more biology meaningful interpretation of Parkinson’s disease. Finally, to study networks related to ovarian cancer recurrence, we investigate two patient data sets. Identified networks from independent data sets show functional consistence. And those common genes and interactions are well supported by current biological knowledge.