Fig. 2

Programming of disease-specific DNA methylation patterns in CLL. a Heatmap depicting DNA methylation changes (ΔMethylation [%]) at CLL-specific CpG sites relative to the samples’ COO. Unsupervised hierarchical clustering of CLL-specific CpGs, class A and B sites (left), class C and D sites (right). The direction of DNA methylation change (Dir [%]) is indicated as blue and red bars for hypo- and hypermethylation, respectively, and the numbers of CpG sites plotted are indicated next to the bars. Differentiation stages (DS) are denoted as a color gradient (white-orange), where CLL samples with immature COO are represented in white and samples with a more mature COO in orange. DS refers to % normal differentiation programming achieved (relative to hiMBCs). b Density plots summarizing the distribution of absolute DNA methylation levels for all CLL-specific CpG sites stratified by class (classes A–D). CLL patients (CLL): orange, naïve B cells (NBC): light green, class-switched memory B cells (hiMBC): dark green. c Box plots and ribbon plots displaying the average DNA methylation change for each class of CLL-specific alterations across normal B cells and CLLs. Left (normal): average DNA methylation change (ΔMeth) of CLL-specific CpGs during normal B cell differentiation from naïve B cells (NBCs) to class-switched memory B cells (hiMBCs) plotted for all classes (classes A [n = 5757 CpG sites], B [n = 183 CpG sites], C [n = 4238 CpG sites], and D [n = 157 CpG sites]). Right (CLL): ΔMeth for CLL-specific CpGs in CLL. ΔMeth [%] is represented as the mean DNA methylation change relative to the expected DNA methylation level of the COO. Standard deviation is depicted as gray shaded ribbons. DS refers to % normal differentiation programming achieved (relative to hiMBCs)