Next, the significant negative miRNA:mRNA correlations were intersected with bioinformatic predictions to identify the most likely direct miRNA:mRNA target interactions. At FDR <0.10, 2445 significant negative correlations were retained. The intersection resulted in the identification of 481 miRNA:mRNA targeting pairs between 25 hub miRNAs and 244 hub mRNAs. Similar to the ME network-level correlations, a clear separation of module miRNAs:mRNA interactions was also detected. For example, miRNAs from the M blue and M yellow modules targeted only the glial cell-associated mRNA modules, M green, M grey60, M pink and M salmon, whereas miRNAs from the M brown targeted only the neuron-associated mRNA modules, M turquoise and M yellow. Within each mRNA module we identified several instances of cooperative miRNA targeting, i.e. multiple miRNAs targeting a single mRNA gene. It has previously been shown that cooperative miRNA regulation of mRNAs leads to an enhanced repressive effect and greater specificity of target regulation [54]. The most prominent case of such cooperative targeting by miRNAs was for AF4/FMR2 family, member 1 (AFF1), which was targeted by 8 miRNAs from miRNA: M blue and
