Fig. 4: Epipolymorphism in normal kidney, ccRCC tissue and 786-O ccRCC cell line.

Schematic explanation of epipolymorphism and average methylation (A). Lollipops represent individual CpGs (black: methylated, white: unmethylated) and an e-locus is defined as four adjacent CpGs (red rectangle). The diagram demonstrates average methylation levels at each CpG, average methylation levels across an e-locus and epipolymorphism. Epipolymorphism measures how variable the methylation pattern is within and between reads. This explains how two samples may have the same average methylation across an e-locus, but different epipolymorphism values. This figure was adapted from [12]. Annotation for e-loci with significant differential epipolymorphism in ccRCC versus normal kidney tissue in the discovery cohort (135 samples; B, C). Annotation for e-loci with significant differential epipolymorphism in ccRCC versus normal kidney in the validation cohort (71 samples; D, E). Epipolymorphism is shown in ccRCC tumour tissue, normal kidney tissue and the 786-O renal cancer cell line for: all e-loci (F), e-loci with significantly higher epipolymorphism in normal kidney (G) and e-loci with significantly higher epipolymorphism in ccRCC (H). I demonstrates epipolymorphism values for selected e-loci in the promoter region of 8 genes which are known to be associated with kidney cancer and were found to have significantly higher epipolymorphism in ccRCC vs normal kidney. These genes were selected to be visualised as an illustrative example.