Extended Figure 7.

Gene co-expression modules in males with MDD are enriched for DEGs across brain regions. a, Topological overlap matrix (TOM) plots for control and b, MDD modules in males. Light color represents low topological overlap and progressively darker red color represents higher overlap. Each module is assigned by a unique color. c, Circos plots displaying the degree of enrichment for DEGs (p<0.05) in male modules. Colors within squares of the plots represent the corrected Fisher’s Exact Test p-value of the enrichment across modules which are depicted in the color bar below the circos plot. Legend on the bottom right corner defines individual layers of the circos plot. d, Peru module in male MDD shows enrichment for DEGs across brain regions. Hubs and nodes are defined by the size of the pie charts with colors representing enrichment for DEGs across brain regions (depicted in the bottom right panel). The star highlights EMX1, which was selected for sex-specific in vivo phenotypic validation studies. e, Schematic representation of the behavioral paradigm used to assess the impact of EMX1 overexpression in the vmPFC of males and females. Bar graph shows the HSV-mediated overexpression of EMX1 covering the infra- and prelimbic region of vmPFC in male mice. f, Behavioral consequence of EMX1 overexpression in the novelty-supressed feeding (NSF) test in males and g, females. Significance in tests e was determined using student independent sample t-test and in f–g using two-way ANOVA with Tuckey correction. e n=5/condition, f–g n=10/condition. Bars, mean ± sem; * p<0.05.