Fig. 5

In vitro and in vivo perturbations of key driver genes in the AD myelin/oligodendrocyte networks validated a number of predicted downstream targets. In these network plots, arrows refer to the predicted direction of interaction in the AD sample-derived core oligodendrocyte Bayesian regulatory network (COLBN). The presence of multiple arrows between two genes is because COLBN was constructed by a union of directed links of three networks from three brain regions. In each plot, the perturbed (i.e., knocked-down or knocked-out) gene is colored yellow, the genes significantly down-regulated in the samples with the driver perturbed are colored green, the genes up-regulated are colored red, and the genes with inconsistent expression changes (i.e., multiple probes corresponding to the same gene show opposite directions of changes in expression) are colored blue. The size of the node is proportional to the number of downstream nodes in the subnetwork. a Validation of the two-layer subnetwork regulated by MYRF using the differentially expressed genes (FDR < 0.3, p < 0.05) derived from a Myrf knockout experiment in cultured mouse oligodendrocytes. b, c, d Validation of the two-layer subnetworks regulated by PLP1, CNP, and UGT8 using the differentially expressed gene signatures (FDR < 0.3, p < 0.05) from the RNAseq data derived from our knockout experiments in mice