Network and pathway enrichment analysis
Network analysis was used to determine the influential role of the identified seed genes within the population affected by HCC and treated with sorafenib.
To consolidate the seed genes, we conducted a gene network consolidation approach like the one proposed in Agapito et al..27The consolidation approach consists of: i) mapping seed genes on the human protein-protein interaction (PPI) network from the Integrated Interactions Database (IID);28 ii) for each mapped seed gene, the expansion process regards the computing of the community with a radius equal to one, allowing the collection of all genes that share similar functions or involvement in similar biological processes with seed genes.29 We used Cytoscape30 and the Cytoscape plugin CytoHubba31 to assess the mapped seed genes’ roles in the “seedGeneNetwork,” computing the degree of the seed genes. The node degree is the sum of all edges connected to it. A node with a degree equal to d indicates that the neighbor radius nodes linking it is d. To further investigate the seed genes list, we computed pathway enrichment analysis to gain insight into the affected unknown underlying biological mechanisms associated with sorafenib response in the 34 HCC patients.
Reactome enrichment analyses were performed using BiP and pathDIP.32,33