Identifying condition-specific modules by clustering multiple networks.

Abstract

Condition-specific modules in multiple networks must be determined to reveal the underlying molecular mechanisms of diseases. Current algorithms exhibit limitations such as low accuracy and high sensitivity to the number of networks because these algorithms discover condition-specific modules in multiple networks by separating specificity and modularity of modules. To overcome these limitations, we characterize condition-specific module as a group of genes whose connectivity is strong in the corresponding network and weak in other networks; this strategy can accurately depict the topological structure of condition-specific modules. We then transform the condition-specific module discovery problem into a clustering problem in multiple networks. We develop an efficient heuristic algorithm for the Specific Modules in Multiple Networks (SMMN), which discovers the condition-specific modules by considering multiple networks. By using the artificial networks, we demonstrate that SMMN outperforms state-of-the-art methods. In breast cancer networks, stage-specific modules discovered by SMMN are more discriminative in predicting cancer stages than those obtained by other techniques. In pan-cancer networks, cancer-specific modules are more likely to associate with survival time of patients, which is critical for cancer therapy.