A new strategy for exploring the hierarchical structure of cancers by adaptively partitioning functional modules from gene expression network

Abstract

The interactions among the genes within a disease are helpful for better understanding the hierarchical structure of the complex biological system of it. Most of the current methodologies need the information of known interactions between genes or proteins to create the network connections. However, these methods meet the limitations in clinical cancer researches because different cancers not only share the common interactions among the genes but also own their specific interactions distinguished from each other. Moreover, it is still difficult to decide the boundaries of the sub-networks. Therefore, we proposed a strategy to construct a gene network by using the sparse inverse covariance matrix of gene expression data, and divide it into a series of functional modules by an adaptive partition algorithm. The strategy was validated by using the microarray data of three cancers and the RNA-sequencing data of glioblastoma. The different modules in the network exhibited specific functions in cancers progression. Moreover, based on the gene expression profiles in the modules, the risk of death was well predicted in the clustering analysis and the binary classification, indicating that our strategy can be benefit for investigating the cancer mechanisms and promoting the clinical applications of network-based methodologies in cancer researches.