Page 129 - 2020_01-Haematologica-web

Intraclonal heterogeneity in CMML
AB
CD
E
F
Figure 6. Methylation profile recapitulates features related to the biology of the chronic myelomonocytic leukemia clones. (A) Unsupervised clustering by corre- spondence analysis showing a clear separation between control, ‘Co’, and chronic myelomonocytic leukemia (CMML) clones ‘A’, using tiles with a standard deviation (SD)>0.03. (B) Supervised analysis (β binomial model) displayed a clear trend toward hypermethylation in CMML clones compared to Co clones. Arrows, percentage of methylation required to be considered as a differentially methylated region (DMR). Red dots, tiles that fulfill the criteria [absolute methylation difference ≥40% and false discovery rate (FDR) <5%]. (C) Heatmap of DMR based on the Euclidean distance matrix. Red, hypomethylation; blue, hypermethylation; gray, DMR that were not covered by enhanced reduced representation bisulfite sequencing in a specific tile. (D) Annotation to genomic regions of background of all tiles (left) and DMR (right). Asterisk, significance according to the binomial test (P<0.001). (E) Gene ontology of DMR methylated on CMML clones. Bar chart: processes related to hematopoiesis with a FDR <0.1. X-axis, -log10 of the FDR. (F) Hierarchical cluster of methylation tiles with the highest SD (SD>0.03). Y-axis, distance metric obtained from the Euclidean distance matrix.
haematologica | 2020; 105(1)
119