We further extracted the NA-specific network from the reference network. It was interesting to note that some additional genes not among the NAGenes but included in the human PPI network, were associated with nicotine addiction. For instance, CAV1, the structural protein of caveolae, can regulate the function of dopamine receptor D1 in glial cells and hippocampal neurons and may participate in G protein-coupled receptor signaling events [53–54]. CANX, a transmembrane protein in endoplasmic reticulum, can mediate intracellular Ca2+ concentration and directly interact with dopamine and G protein-coupled receptors to regulate their expression (Table 3) [55–56]. As indicated by the results, network-based analysis could not only provide meaningful information about the organization and environment of NAGenes, but also be promising to identify novel candidate genes. Although the quantity and quality of PPI data have been greatly improved, the human PPI network is still far from complete. In such scenario, some proteins may simply have more interaction information than others because they are better studied, instead of they are biologically more important. Also, due to the limitation of current technology, there may
