Fig. 2
From: DNA methylation signature of human hippocampus in Alzheimer’s disease is linked to neurogenesis
Characterization of AD-related DMPs. a The histogram of beta difference value distribution per CpGs shows a clear bias toward the hypermethylated changes (> 0.0) in AD hippocampal samples compared to controls. b The volcano plot shows a greater number of hypermethylated marks (red dots) compared to hypomethylated marks (blue dots) that crossed the statistical thresholds (dotted lines) in this study. The graph also shows that DNA methylation changes in AD hippocampus are mild to moderate in effect size. c The heat map graph reveals that most of the DNA methylation changes represent gains (red squares) in methylation. d Distribution of DMPs regarding gene structure. The bar graph shows the log2 ratios of observed (fraction of differentially methylated probes that overlap a particular region) to expected (fraction of probes selected for analysis that overlap a particular region). S = south, N = north, TSS = transcription start site. e Differential analysis revealed up to 8 AD-related DMPs located within the HOXA genes cluster in the short arm of chromosome 7. The upper tracks show 450K microarray values and results of differential analysis. Blue dots represent per CpG median β-values for patients and controls. Vertical red bars represent β-difference values for CpGs included in the DMPs that crossed the statistical threshold (β-difference > 0.1 and p value < 0.05). Grey bars represent β-difference values for the CpGs included in the DMPs. Methylation values are aligned to ENCODE/Broad data for H3K27me3 histone marks in H1 human Embryonic Stem Cells (H1-hESC) at the bottom. f Dot plot graphs show 450K microarray β-values for the CpGs with most significant p value for each 4 genes within DMPs in the HOXA cluster. The selected CpGs are as follow, HOXA2: cg04027736, HOXA3: cg22962123, HOXA4:cg16651126, EVX1:cg08865099. g Extended mapping of hypermethylated DMPs within HOXA3 gene in 2 AD cases (below) compared to 2 controls (above) obtained by bisulfite cloning sequencing that shows how differential methylation affects multiple contiguous CpGs. The amplicon overlaps cg00921266 (blue arrow) and cg22962123 (red arrow). Black circles represent methylated cytosines while white circles denote unmethylated cytosines. Each column symbolizes a unique CpG site in the examined amplicon, and each line represents an individual DNA clone. Average percentage of methylation for each analyzed sample (control or patient) at this particular amplicon is indicated at the bottom of each sample