Drivergene.net: A Cytoscape app for the identification of driver nodes of large-scale complex networks and case studies in discovery of drug target genes.

There are no tools to identify driver nodes of large-scale networks in approach of competition-based controllability. This study proposed a novel method for this computation of large-scale networks. It implemented the method in a new Cytoscape plug-in app called Drivergene.net. Experiments of the software on large-scale biomolecular networks have shown outstanding speed and computing power. Interestingly, 86.67% of the top 10 driver nodes found on these networks are anticancer drug target genes that reside mostly at the innermost K-cores of the networks. Finally, compared method with those of five other researchers and confirmed that the proposed method outperforms the other methods on identification of anticancer drug target genes. Taken together, Drivergene.net is a reliable tool that efficiently detects not only drug target genes from biomolecular networks but also driver nodes of large-scale complex networks. Drivergene.net with a user manual and example datasets are available https://github.com/tinhpd/Drivergene.git.

Identification of anticancer drug target genes using an outside competitive dynamics model on cancer signaling networks.

Each cancer type has its own molecular signaling network. Analyzing the dynamics of molecular signaling networks can provide useful information for identifying drug target genes. In the present study, we consider an on-network dynamics model-the outside competitive dynamics model-wherein an inside leader and an opponent competitor outside the system have fixed and different states, and each normal agent adjusts its state according to a distributed consensus protocol. If any normal agent links to the external competitor, the state of each normal agent will converge to a stable value, indicating support to the leader against the impact of the competitor. We determined the total support of normal agents to each leader in various networks and observed that the total support correlates with hierarchical closeness, which identifies biomarker genes in a cancer signaling network. Of note, by experimenting on 17 cancer signaling networks from the KEGG database, we observed that 82% of the genes among the top 3 agents with the highest total support are anticancer drug target genes. This result outperforms those of four previous prediction methods of common cancer drug targets. Our study indicates that driver agents with high support from the other agents against the impact of the external opponent agent are most likely to be anticancer drug target genes.