Fig. 7: Prominent association of human/macaque-biased CREs with risk SNPs of various brain disorders.
From: Single-cell spatial map of cis-regulatory elements for disease-related genes in the macaque cortex
a Dot plot showing the ranked distribution of human/macaque-biased vs. mammal-conserved CRE ratios (with disease-risk SNPs) across cell subclasses. Cell types with fold changes below the background are shown with reduced transparency. The violin plot (upper left) illustrates comparisons between glutamatergic neurons, GABAergic neurons, and non-neuronal cells. P values were calculated using a two-sided Wilcoxon rank-sum test (*** P < 0.001). For Glut. Vs GABA., P < 2.22 × 10-16; Glut vs non-neurons, P = 2 × 10-8. b Ridge plot depicting the chromatin accessibility of human/macaque-biased and mammal-conserved CREs (colocalized with SCZ risk SNPs) in the L4_3 glutamatergic cluster. Significant difference was calculated by a two-sided Student’s t-test. c Venn Diagram showing the overlap of genes associated CREs in b. d Bar plot illustrating the relative chromVAR deviations of CREs in b. The sample sizes are listed in Supplementary Data 10. Error bars represent SEM. e Gene regulatory network (GRN) showing the key transcription factors (TFs) for targeted genes linked to CREs associated with SCZ risk SNPs in L4_3 neuron. SCZ ontology genes were labeled. f Genome browser tracks showing chromatin accessibility in L4_3 neurons at SCZ risk SNP-associated CREs linking to GFRA2 and NEFH, respectively. g Box plot showing the ranked distribution of the fold change in the relative composition of human/macaque-biased versus mammal-conserved CREs across various brain disorders. The sample sizes are listed in Supplementary Data 10. Significant difference was observed by two-sided Wilcoxon rank-sum test. Center line, median; box limits, 25th–75th percentiles; whiskers, 1.5 × IQR; points beyond, outliers. h Venn Diagram illustrating the overlap of genes associated with human/macaque-biased and mammal-conserved CREs in microglia cells. i Pathways enriched by genes linking to AD risk SNP associated CREs in microglia. j Genome browser tracks plot showing chromatin accessibility in microglia at the AD risk SNP associated CREs linked genes in h. k Dot plot illustrating the relative chromVAR deviations of human/macaque-biased and mammal-conserved CREs (colocalized with AD risk SNPs) across brain lobes in microglia.
