roughly grouped into three major modules, each of which included pathways shared more crosstalks compared with other pathways and may likely be involved in the same or similar biological process (Fig 1). One module mainly consisted of neurodevelopment-related signaling pathways, such as glutamate receptor signaling, synaptic long term potentiation and CREB signaling in neurons. The second module was primarily dominated by immune system-related pathways, including role of cytokines in mediating communication between immune cells, T helper cell differentiation and others. Another module composed of the metabolic pathways of neurotransmitters or drug, such as nicotine degradation II, dopamine degradation and serotonin degradation, the roles of these pathways in nicotine addiction have not been fully explored. As indicated by the above results, pathway crosstalk analysis can provide important insights for understanding of nicotine addiction mechanisms.
