Allele-specific DNA methylation profiling. Unsupervised cluster analysis was performed on the CpG methylation pattern obtained for each sample and amplicon. When a heterozygous SNP was observed, sequence reads were separated accordingly to the SNP genotype, and the CpG methylation pattern of each allele was analyzed by cluster analysis. (A) Differential methylation between alleles at region 9 in the healthy donor C55. (i) Overall cluster analysis identified 2 clusters according to the methylation pattern; (ii) DNA methylation pattern for each allele. (B) Allele-specific DNA methylation differences at region 2 between diagnosis (i) and complete remission (ii) stages of patient P9 with APL; (iii) allele-specific DNA methylation at region 2 in the healthy donor C55. (C) Allele-specific DNA methylation differences at region 7 between diagnosis (i) and complete remission (ii) stages of patient P31 with APL; (iii) allele-specific DNA methylation at region 7 in the healthy donor C52. Heat maps show clustering results. Each column represents a CpG site, and each row the methylation pattern of a single sequence read. The color indicates the methylation status of each CpG: blue, methylated; yellow, not methylated. The bar plot at the top of each heat map shows the overall methylation level of each CpG site.