The purpose of correlating mRNA and miRNA MEs was to investigate whether general correlation patterns could be detected at the gene network level. As MEs are representative of module-wide gene expression profiles, this analysis gives a global perspective of miRNA:mRNA interactions in our AD sample. Although the strongest correlations between mRNA and miRNA MEs were positive (ranging between r = 0.63 and 0.75), negative correlations were also prominent (ranging between r = -0.37 and -0.56) (Fig 4). After assessing miRNA:mRNA ME correlations, our next step was to examine the individual miRNA:mRNA hub gene interactions driving the module correlations. The Pearson correlations between 518 transcripts, representing the 461 mRNA hubs and 25 miRNA hubs, resulted in 12,950 correlations (S6 Table), of which a higher number of positive versus negative correlations were observed (59% vs. 41%; χ2 p≤ 0.0001). Interestingly, Nunez, et al. (2013) reported similar findings in a mouse model of AD where miRNA:mRNA positive correlations were more abundant than negative correlations [22]. It is unclear, however, whether these positive correlations represent direct miRNA upregulation of target mRNAs or secondary effects
