D-aspartate 2A (GRIN2A), GRIN2B, GRIN3A, calcium/calmodulin-dependent protein kinase IV (CAMK4), CREB1, and glutamate receptor metabotropic 7 (GRM7), suggesting these genes might be more potential targets in the development of nicotine addiction. In addition, the pathway pair of cAMP-mediated signaling and G-protein coupled receptor signaling, which were not included in the three modules, was also noteworthy. In the pathway analysis, we found these two pathways stood out at the top of the list by the statistically significant level (PBH = 2.00×10–14, ranked 1st and PBH = 3.16×10–13, ranked 3rd, respectively) (S2 Table). And the score of this pathway pair was 0.94, ranking the first. Furthermore, these two pathways have been deeply studied for their functions in the nervous system, such as regulating pivotal physiological processes. It was worth noting that, several edges, linking any one of these two pathways and other significant pathways were not displayed in Fig 1 just because they did not meet our criteria, such as the link between cAMP-mediated signaling and dopamine receptor signaling. In this study, we just empirically chose the pathway pairs whose crosstalk score fell within the top 20%, therefore some pathway pairs which we might be interested in were not shown in Fig
