Fig. 4

Top differentially-accessible peaks (DAPs) upregulated and down-regulated in LOAD by cluster and cell type. a, UMAP dimensional reduction plot of snATAC-seq cell data indicating both cell type and subtype clusters. Clusters highlighted in panel b are circled in red. b, Unbiased volcano plots for four example clusters representing excitatory neuron, inhibitory neuron, and microglia cell types. Log₂ fold change (FC) between LOAD and normal control (NC) samples is plotted against—log₁₀ p-value (FDR). Points representing DAPs with statistically significant (p < 0.05) upregulation of accessibility in LOAD are shown in green while DAPs with significant downregulation are shown in red. Peaks without significantly differential accessibility are shown in blue. The proportion of DAPs to total peaks examined is shown above each plot. The closest genes to the six DAPs with the highest absolute fold change (log₂ FC > 0.2) in the more and less accessible categories are labeled in green and red, respectively. The closest genes to the top more and less accessible DAPs within 500 kb of GWAS SNPs are labeled in teal and pink, respectively. Distances of closest genes from corresponding peaks (in bp) are indicated adjacent to gene labels where such distances are greater than zero. For each of the labeled peaks, dot plots are shown below representing their unscaled accessibility levels (color) and percent of cells with identified peak accessibility (width) for LOAD and NC samples. c, Heatmap showing log₂ FC for the top three DAPs (log₂FC > 0.2 in at least one cell type) with the highest fold changes in upregulated (green) and down-regulated (blue) categories for each cell type examined, as well as the top three DAPs (log₂FC > 0.2 in at least one cell type) within 500 kb of identified GWAS SNPs (labeled in purple). Closest gene names are indicated to the left of the heatmap while peak ranges are shown to the right. d, Table comparing cell type-level DAPs identified in this study to those of Morabito et al. [43] e, Venn diagrams showing overlap between DEGs identified via snRNA-seq and DAPs identified via snATAC-seq for each cell type examined