Fig. 5: Analysis of chromatin accessibility and regulatory elements involved in cocaine dependence.
a, Pseudobulk chromatin accessibility at the promoter regions of marker genes for main cell types. b, Significant DEGs (FDR < 10%) for each main cell type are enriched for promoters with DA chromatin. Points are log2OR (odds ratio) and error bars are 95% CIs (FDR < 10%; two-sided FET, n = 12,081 genes for astrocytes, n = 12,590 for ExNeuron, n = 12,679 for InhNeuron, n = 11,232 for microglia, n = 11,886 for oligodendrocytes and n = 11,646 for OPC). This indicates that the snRNA-seq and snATAC-seq results are consistent and that gene expression changes are associated with changes in promoter chromatin accessibility. c, Cell-type-specific DA peaks are enriched in TSS/promoter regions compared with non-TSS/promoter regions. Points are log2OR and error bars are 95% CIs (FDR < 10%; two-sided FET, n = 291,844 peaks) d, Heatmap showing differential activity of various motifs in the significant differential peaks of each cell type. Values indicate average difference of chromVAR deviation scores with –log10(Q) in parentheses, where Q is the Benjamini–Hochberg FDR-corrected P value from a two-sided Wilcoxon signed rank test for difference in deviation scores. There are many cases where motifs display increased activity in upregulated peaks in neurons while also displaying decreased activity in downregulated peaks in oligodendrocytes. e–g, Volcano plots showing average (mean) difference (x axis) and –log10(Q) (y axis) of chromVAR deviation scores for the top 50 motif clusters in excitatory neurons (e), inhibitory neurons (f) and oligodendrocytes (g). h, LD score regression results showing significance of enrichment of heritability for several traits related to alcohol and nicotine addiction in cell-type-specific accessible chromatin regions (mapped to hg19). Significance is reported as –log10(Q), where Q is the Benjamini–Hochberg FDR-corrected P value obtained from the ldsc software98.
