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