To distill insight into the interaction of NAGenes in a local environment, we extracted the specific subnetwork of nicotine addiction (NA-specific network) from the human PPI network using the Steiner minimal tree algorithm. Basically, this approach linked as many as possible members of NAGenes via the minimal number of connections. As shown in Fig 2, the subnetwork contained 252 nodes and 591 edges. Of the 220 NAGenes, 208 were included in the NA-specific network, which accounted for approximately 94.5% of the candidate genes and 82.5% of the genes in the NA-specific network, indicating a high coverage of NAGenes in the subnetwork. Of note, some of the 44 additional genes, e.g., calmodulin 2 (CALM2), calnexin (CANX), caveolin-1 (CAV1), glutathione S-transferase omega 1 (GSTO1) and protein phosphatase 1 (PPP1CA), had been reported to be associated with addiction in previously studies (Table 3) [33–34].
