Single-cell network biology characterizes cell type gene regulation for drug repurposing and phenotype prediction in Alzheimer’s disease
Fig 5
Coregulated gene modules reveal cell type-specific drug-repurposed targets and gene functions in AD.
(A) Illustration depicting the concept of gene set cohesiveness in a network. The bar plot below shows the number of gene ontology biological process terms (y-axis) that gain (blue) or lose (red) cohesiveness between control and AD networks across all cell types (x-axis; see Methods). (B) A heatmap showing the enrichment of co-regulated modules of the microglia AD network within differentially expressed genes in various AD pathologies. The average fold-change of genes within each module was transformed to a Z-score to derive the enrichment score. Negative and positive Z-scores indicate down- and up-regulation, respectively, of co-regulated modules (x-axis) in AD pathologies (y-axis). The grids of the heatmap are colored accordingly, with red indicating down-regulation and blue indicating up-regulation of the module. (C) Visualization of genes in module 1 of the microglia AD coregulatory network. Each circle in the plot is a gene, with TFs depicted as triangles, known AD-genes in octagons, and other genes as ellipses. Nodes are colored according to fold change values in AD pathology (early versus no pathology) as shown in the key. (D) Proposed mechanism-of-action for treatment of AD by everolimus using drug-target network analysis with microglia M1. (E) Proposed mechanism-of-action for treatment of AD by Rifampcian using drug-target network analysis with microglia M4.