Networks were created from each cluster of microRNAs and their associated targets DE at any time point, emphasizing those targets dysregulated at 120h (S4 Fig). Notably, genes identified as hubs in the cluster-based networks (Table 6) were also identified as hubs in the network analysis of paired microRNAs and 120h DE targets. For example, Bcl2 showed high connectivity in AMY networks created from both approaches; similarly, for Srf in PFC networks. Additionally, hub genes from the cluster-based networks were also essential members of the combined networks described above. These included Bcl2 in AMY, Mapt in NAC and Fndc3b in PFC (Tables 5 and 6). In general, cluster-based networks exhibited varying degrees of overlap with critical network genes identified in the time point-based analysis (Table 5). The greatest overlap occurred between Table 5 genes and AMY cluster 4 (13/21 genes), NAC cluster 3 (9/14 genes) and PFC cluster 4 (10/13 genes) (S5 Fig). MicroRNAs and mRNAs identified by both cluster- and time point-based approaches are highlighted in Fig 8.
