Identifying potential drug targets in hepatocellular carcinoma based on network analysis and one-class support vector machine.

Hepatocellular carcinoma (HCC) is one major cause of cancer-related death worldwide. But now, the systematic therapy for the advanced stages of HCC is rather limited. Thus, the discovery of novel drug targets and thereafter targeted drugs against HCC is continuously needed. In this study, we combined clinical association data, gene expression profiles and manually collected drug target genes with the human protein-protein interaction (PPI) network to establish an in-silico HCC drug target predictor. First, we found drug target genes (DTGs), disease-associated genes (DAGs), prognostic unfavorable genes (PUGs) and cancer up-regulated genes (URGs) have higher degree, betweenness, closeness centrality, while cancer down-regulated genes (DRGs), prognostic favorable genes (PFGs) have lower degrees, in comparison with background genes. Moreover, DTG nodes were shown to be closer to DAG, PUG and URG nodes, but farther away from PFG and DRG nodes. Compared to the background, PFGs and DRGs were shown to have relatively bigger genetic dependency scores, while PUGs and URGs have smaller genetic dependency scores. Finally, based on the observed features of DTGs, we constructed a drug target predictor using one-class support vector machine (one-class SVM). Performance evaluation results suggested our predictor could effectively identify putative drug target genes for further research.