Fig. 5: VOGM genes converge in a VEGFR-Ras signaling network in fetal cerebral endothelial cells.
From: Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations
a Enrichment in VOGM gene modules of the fetal human cortex, compared to other disease genes. Numbers displayed exceed the Bonferroni-corrected statistical significance threshold tested by one-sided Fisher’s exact test and are -log10(p-value). Height: human height; MMD: moyamoya disease; CCM: cavernous malformation; AVM_VOGM: arteriovenous malformation and vein of Galen aneurysmal malformation; VOGM: high-confidence vein of Galen aneurysmal malformation gene set; pVOGM: probable VOGM gene set; AVM: arteriovenous malformation (see Methods for gene set details). b Temporal dynamics of modules enriched with VOGM genes. Peak expression of “Midnight Blue” module is at post-conception week (PCW) 37. Both the “Black” and “Green-yellow” modules exhibited peak gene expression early in development at PCW 9-17. “Light Cyan” module is expressed much later at postnatal age 10–12 months. c Gene Ontology (GO) biological processes and WikiPathways of midnight blue module converge on Focal Adhesion-PI3K-Akt-mTOR Signaling Pathway, Positive Regulation of Vascular Development, and Regulation of Cell Migration (one-sided Fisher’s exact test, Bonferroni multiple-testing adjusted). The significance threshold is denoted by the vertical dashed line. Top enriched terms have bolded text and purple bars. d Cell-type enrichment of VOGM and other disease genes in the fetal human cortex. Numbers displayed exceed the Bonferroni-corrected statistical significance threshold tested by one-sided Fisher’s exact test and are -log10(p-value). Different cell types are noted on the x-axis, see text for details. e Cell-type enrichment of VOGM genes in the developing human cerebrovasculature. Numbers displayed exceed the Bonferroni-corrected statistical significance threshold tested by one-sided Fisher’s exact test and are -log10(p-value). Different cell types are noted on the x-axis (see text for details). f Enrichment of disease genes in fetal human cortex modules. Numbers displayed exceed the Bonferroni-corrected statistical significance threshold tested by one-sided Fisher’s exact test and are -log10(p-value). g GO molecular function and WikiPathways analyses of enriched module 11 and 12 (one-sided Fisher’s exact test, Bonferroni multiple-testing adjusted). The significance threshold is denoted by the vertical dashed line. Enriched terms of interest have bolded text and purple bars.
