Figure 2.
Figure 2. Genome-wide DNA methylation analysis and BCR repertoires in BCP-ALL monozygotic twins. (A) Violin plots depicting the global DNA methylation levels (β-value distributions) of CpG sites identified by WGB-seq. For healthy BCPs, the average DNA methylation value of 2 FL-derived pools of BCP is represented. (B) Total number of differentially hyper- (hyper) and hypomethylated (hypo) CpGs observed for the indicated comparisons between twins and healthy BCPs. The inner graph represents the total number of differentially methylated CpG (dmCpG) sites. (C) Stacked bar plots indicating the relative proportion of significant hyper- and hypomethylated CpGs between twins, or between each twin and healthy BCPs, regarding their CpG context (left) or the CpG genomic location (right), respectively, as indicated in the colored legend. (D-E) Ideograms representing the genomic location of differentially DNA hypermethylated (D) and hypomethylated (E) CpG sites obtained for twin A (pink) and twin B (blue) as compared with healthy BCPs. (F) Cartoon summarizing how BCR-seq captures IgH sequences across B-cell stages/development. (G) Network plots of BCR repertoires of a representative healthy donor (HD) and an infant mixed-lineage leukemia–rearranged (rMLL) pro-B ALL depicting the existence of many minor diagnostic nonexpanded B-cell clones (top middle left). Network plots of BCR repertoires of a representative t(12;21)/ETV6-RUNX1+ and t(1;19)/TCF3-PBX1+ pediatric BCP-ALL showing high clonality of B-cell clones (top middle right). Network plots of BCR repertoires of TCF3-ZNF384–rearranged pro-B ALL in both monozygotic twins (bottom). Each vertex represents a unique BCR sequence, and relative vertex size is proportional to the number of identical reads. For the HD and BCP-ALL twin samples, each vertex is represented by a pie chart indicating the percentage of each isotype, where blue = IgD/M, red = IgA1/2, yellow = IgG1/2, green = IgG3, and gray = IgE. (H) Boxplots of the largest and second largest BCR clone sizes for HD, non-t(4;11)+ BCP-ALL, and twins with concordant BCP-ALL. (I) Histogram representing the number of BCR clones shared between twin A and twin B (blue) or between unrelated HD and the twins (red).

Genome-wide DNA methylation analysis and BCR repertoires in BCP-ALL monozygotic twins. (A) Violin plots depicting the global DNA methylation levels (β-value distributions) of CpG sites identified by WGB-seq. For healthy BCPs, the average DNA methylation value of 2 FL-derived pools of BCP is represented. (B) Total number of differentially hyper- (hyper) and hypomethylated (hypo) CpGs observed for the indicated comparisons between twins and healthy BCPs. The inner graph represents the total number of differentially methylated CpG (dmCpG) sites. (C) Stacked bar plots indicating the relative proportion of significant hyper- and hypomethylated CpGs between twins, or between each twin and healthy BCPs, regarding their CpG context (left) or the CpG genomic location (right), respectively, as indicated in the colored legend. (D-E) Ideograms representing the genomic location of differentially DNA hypermethylated (D) and hypomethylated (E) CpG sites obtained for twin A (pink) and twin B (blue) as compared with healthy BCPs. (F) Cartoon summarizing how BCR-seq captures IgH sequences across B-cell stages/development. (G) Network plots of BCR repertoires of a representative healthy donor (HD) and an infant mixed-lineage leukemia–rearranged (rMLL) pro-B ALL depicting the existence of many minor diagnostic nonexpanded B-cell clones (top middle left). Network plots of BCR repertoires of a representative t(12;21)/ETV6-RUNX1+ and t(1;19)/TCF3-PBX1+ pediatric BCP-ALL showing high clonality of B-cell clones (top middle right). Network plots of BCR repertoires of TCF3-ZNF384–rearranged pro-B ALL in both monozygotic twins (bottom). Each vertex represents a unique BCR sequence, and relative vertex size is proportional to the number of identical reads. For the HD and BCP-ALL twin samples, each vertex is represented by a pie chart indicating the percentage of each isotype, where blue = IgD/M, red = IgA1/2, yellow = IgG1/2, green = IgG3, and gray = IgE. (H) Boxplots of the largest and second largest BCR clone sizes for HD, non-t(4;11)+ BCP-ALL, and twins with concordant BCP-ALL. (I) Histogram representing the number of BCR clones shared between twin A and twin B (blue) or between unrelated HD and the twins (red).

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