Fig. 2

Example of a tri-modal pattern of β values distribution. a. Upper panel: Individual β values for 36 cell lines examined using the probe type II (cg23556238) interrogating CpG site with a SNP (C>T) in the first position. Vertical axis — individual β values; horizontal axis — individual cell lines. Samples 1–18 – East Asian population, samples 18–36 –European population. High, low, and intermediate β values are observed, respectively, in the cell lines with CpG (blue), TpG (yellow) and CpG/TpG (red) genotypes. The tri-modal distribution is that of beta values (along the Y axis). Lower panel: Box plot graph showing fluorescence readouts for the probe cg23556238. The normalized signals (values indicated on the vertical axis) are detected as a result of probe extension with differently labelled dideoxynucleotides: green and red, indicating methylated and unmethylated status, respectively. All lines with homozygous CpG genotypes display strong green and no red signal, indicating methylated status; lines with homozygous TpG genotypes display strong red and no green signal, mimicking unmethylated status; heterozygotes have equal intensity of both red and green fluorescence signals. Each boxplot represents interquartile range of the signals from all the probes for a given cell line. The bottom and top of the box represent the first and the third quartile, respectively, and the black line inside the box corresponds to the median. Black circles in the upper part of the graph are outlier values (>1.5 distance from the upper quartile). b. Sequence of the Infinium II probe (cg23556238), aligned with the genomic sequence. According to TpG genotype, dideoxy-A will be incorporated giving red fluorescence signal falsely indicating unmethylated status. “RC” in the probe sequence represents degenerated sites complementary to under-a-probe CpGs (“YG” in the BCD sequence indicates no assumption of the concordant methylation with the interrogated dinucleotide)