To take a further step beyond identifying lists of significantly enriched pathways and to understand how they interact with each other, we performed a pathway crosstalk analysis among the 97 significantly enriched pathways. The approach was based on the assumption that two pathways were considered to crosstalk if they shared a proportion of NAGenes [16]. There were 74 pathways containing 5 or more members in NAGenes, of which, 72 pathways met the criterion for crosstalk analysis, i.e., each pathway shared at least 3 genes with one or more other pathways. There were a total of 380 pathway pairs (edges) from the 72 pathways and then we ranked these edges according to the average scores of the JC and the OC. Ultimately, we chose the top 20% edges to construct the pathway crosstalk. Based on their crosstalk, the pathways could be 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,
