Network diffusion with centrality measures to identify disease-related genes

Abstract

Disease-related gene prioritization is one of the most well-established pharmaceutical techniques used to identify genes that are important to a biological process relevant to a disease. In identifying these essential genes, the network diffusion (ND) approach is a widely used technique applied in gene prioritization. However, there is still a large number of candidate genes that need to be evaluated experimentally. Therefore, it would be of great value to develop a new strategy to improve the precision of the prioritization. Given the efficiency and simplicity of centrality measures in capturing a gene that might be important to the network structure, herein, we propose a technique that extends the scope of ND through a centrality measure to identify new disease-related genes. Five common centrality measures with different aspects were examined for integration in the traditional ND model. A total of 40 diseases were used to test our developed approach and to find new genes that might be related to a disease. Results indicated that the best measure to combine with the diffusion is closeness centrality. The novel candidate genes identified by the model for all 40 diseases were provided along with supporting evidence. In conclusion, the integration of network centrality in ND is a simple but effective technique to discover more precise disease-related genes, which is extremely useful for biomedical science.

Keywords

• protein-protein interaction network
• disease-related genes
• diffusion
• centrality