Figure 2
Figure 2. Characteristics of the APL methylome. (A) Methylation differences of CpG sites within DMRs were confirmed with Infinium 450K bead arrays. The smoothed scatter plot visualizes the methylation differences of APLs and controls in RRBS (x-axis) and the respective methylation differences in Infinium bead arrays (y-axis). A total of 851 DMRs were included in the analysis. (B) Chromosomal distribution of clusters and DMRs. The curves show the density distribution of hypomethylated and hypermethylated DMRs and CpG clusters in relation to their chromosomal position: 0 indicates chromosomal ends and 1 the centromeric region. Hypomethylated DMRs (green), hypermethylated DMRs (red), and CpG clusters (black) are shown. The distribution of DMRs is shifted toward chromosomal ends. (Kolmogorov-Smirnov test: P < .001). (C) Enrichment of genomic regions in DMRs. Briefly, the number of centers of a particular region of interest (eg, the gene promoter) that we could expect in DMRs under the assumption of uniform distribution (expected region centers) was subtracted from the number of region centers actually found in DMRs (observed region centers). The plot shows the differences of observed and expected region centers in hypomethylated DMRs (green bars) and in hypermethylated DMRs (red bars). Two-sided binomial test: significance levels of 1 × 10-2 (**), or 5 × 10-2 (*), respectively. (D) Standard deviation of methylation in APL and healthy controls. The plot shows the standard deviation values of smoothed methylation levels in APL and control samples, respectively. (E) Methylation of DMRs associated with age in APL. Heat map showing the methylation alterations within age-specific DMRs. Depicted DMRs exhibited at least 0.1% methylation difference per year (655 DMRs). (F) Methylation of DMRs associated with Flt3 mutational status. Heat map showing the methylation alterations within Flt3-mutation specific DMRs. Depicted DMRs exhibited at least 30% methylation difference between groups (317 DMRs). (G) Methylation of DMRs associated with risk group. Heat map showing methylation alterations within Sanz score–specific DMRs. Depicted DMRs exhibited at least 30% methylation difference between groups (173 DMRs).

Characteristics of the APL methylome. (A) Methylation differences of CpG sites within DMRs were confirmed with Infinium 450K bead arrays. The smoothed scatter plot visualizes the methylation differences of APLs and controls in RRBS (x-axis) and the respective methylation differences in Infinium bead arrays (y-axis). A total of 851 DMRs were included in the analysis. (B) Chromosomal distribution of clusters and DMRs. The curves show the density distribution of hypomethylated and hypermethylated DMRs and CpG clusters in relation to their chromosomal position: 0 indicates chromosomal ends and 1 the centromeric region. Hypomethylated DMRs (green), hypermethylated DMRs (red), and CpG clusters (black) are shown. The distribution of DMRs is shifted toward chromosomal ends. (Kolmogorov-Smirnov test: P < .001). (C) Enrichment of genomic regions in DMRs. Briefly, the number of centers of a particular region of interest (eg, the gene promoter) that we could expect in DMRs under the assumption of uniform distribution (expected region centers) was subtracted from the number of region centers actually found in DMRs (observed region centers). The plot shows the differences of observed and expected region centers in hypomethylated DMRs (green bars) and in hypermethylated DMRs (red bars). Two-sided binomial test: significance levels of 1 × 10-2 (**), or 5 × 10-2 (*), respectively. (D) Standard deviation of methylation in APL and healthy controls. The plot shows the standard deviation values of smoothed methylation levels in APL and control samples, respectively. (E) Methylation of DMRs associated with age in APL. Heat map showing the methylation alterations within age-specific DMRs. Depicted DMRs exhibited at least 0.1% methylation difference per year (655 DMRs). (F) Methylation of DMRs associated with Flt3 mutational status. Heat map showing the methylation alterations within Flt3-mutation specific DMRs. Depicted DMRs exhibited at least 30% methylation difference between groups (317 DMRs). (G) Methylation of DMRs associated with risk group. Heat map showing methylation alterations within Sanz score–specific DMRs. Depicted DMRs exhibited at least 30% methylation difference between groups (173 DMRs).

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