Correlation between differentially methylated CpGs (DMCs) and gene expression. (A) The functional genomic annotation of DMCs that are correlated with gene expression. The columns show hypermethylated DMCs in red and hypomethylated DMCs in blue, with the number of DMCs correlated with up-regulation (+) or down-regulation (-) of gene expression indicated by the numbers in the panel. The rows show the genomic annotation of the DMCs in relation to gene region, CpG island annotation, and chromatin marks in reference cell types. The fold enrichment of the DMCs within each annotation class is shown to the right of each row. The bolded numbers indicate enrichment compared to the distribution of probes on the 450k array (Bonferroni corrected one-sided Fisher’s exact P < 0.001). (B) Examples of genes with a strong correlation between their expression levels and the β-values of constitutive DMCs (upper left panel) and subtype-specific DMCs (all other panels). The ALL subgroup highlighted and the gene name and structure are outlined above each panel. The positions of the CpG sites correlated with gene expression (permuted P < 0.05) are indicated by black lines connecting the gene structure to the heatmap below. For each gene, the mean β-value of the probes is plotted in the heatmap for the non-leukemic cell types and ALL subtypes as indicated to the left of the heatmap. At the bottom of each panel, the mRNA expression levels are plotted on the y-axis and β-values for the highest ranking CpG site in each gene are plotted on the x-axis. Each individual sample of the subtype analyzed is indicated by red circles and other subtypes are indicated by black circles. The correlation coefficient and CpG ID are shown in each panel. The color keys for the methylation heatmap and CpG island annotation are shown at the bottom left-hand corner of the figure.