Fig. 1

Workflow of the analyses performed in this study. Human postmortem AD brain tissue samples from multiple brain regions were used to construct coexpression networks (a) using Weighted Gene Coexpression Network Analysis (WGCNA). The oligodendrocyte/myelination enriched coexpressed gene modules from WGCNA were annotated by a variety of external data sets including DNA, RNA, proteomic, cell type, and proteome compartment data (b). Next, Bayesian gene regulatory networks were constructed based on the DNA and RNA postmortem human AD data (c). The Bayesian networks were used to identify key driver genes and several key drivers were perturbed in mouse models to identify their downstream targets (d). The gene signatures in response to the perturbations of the key driver genes were used to validate the network structure (e) and to compare with the differential expression patterns in human AD postmortem brains (f)