Fig. 2: Network-based inference of the functional impact of 3q29Del on the adult human prefrontal cortex (PFC).
From: Convergent and distributed effects of the 3q29 deletion on the human neural transcriptome
a Hierarchical clustering of module eigengenes (ME) that summarize the 19 modules identified by WGCNA. The 21 protein-coding genes located in the recurrent 3q29Del locus were found to be distributed into seven co-expression modules (3q29 modules; framed), The numbers next to dendrogram branches indicate the total number of 3q29 interval genes found in each 3q29 module. b Heatmap representing the strength of Pearson’s correlation (r) between ME-pairs. The seven 3q29 modules (arrows) further clustered into three higher-level meta-modules, corresponding to squares of blue color (high positive correlation) along the diagonal, also detected as major dendrogram branches in (a). c Eigengene-based connectivity strength (kME; y-axis) of 3q29 interval genes (x-axis; in chromosomal order) within their respective modules. kME is defined as the Pearson’s correlation between a query gene and a given ME. The line graph indicates the −log10(P value) of the plotted correlation coefficients (z-axis); the asterisks above the graph indicate P < 0.05. kME >0.8 (P < 0.05; dotted line) indicates hub (highly connected) gene status. UBXN7 (red frame) was found to be the only hub gene (kME >0.8, P = 8.33E-30) within the 3q29Del locus. SMCO1 (kME = 0.11, P = 0.25), SLC51A (kME = 0.17, P = 0.09), and MFI2 (kME = 0.09, P = 0.35) were found to have non-significant kMEs (P > 0.05) for their respective modules, suggesting peripheral membership. Color indicates module label. d Top ten biological pathways (Reactome database) significantly enriched in 3q29 modules (adjusted-P < 0.05; capped at −log10 (adjusted-P = 10)). The g:SCS method was used for multiple testing correction. The observed enrichment profile of the queried modules for known biological processes and pathways indicates that genes co-clustering in 3q29 modules show coordinated expression and converge upon overlapping biological functions, more than expected by chance. The functional associations of gene sets comprising individual 3q29 modules were leveraged to infer likely molecular consequences of 3q29Del in the adult human PFC.
