Figure 4

Heatmaps over risk CpGs. (a-c) Heatmaps of COPA-transformed methylation values for the top 140 risk CpGs that are (i) significantly hypermethylated with age and (ii) show significant increased variability in future CIN2+ cases, as determined in the ARTISTIC cohort. Color codes for COPA scores: yellow = COPA score < 1 (no methylation); skyblue = COPA score < 5. Outliers denoted by blue = methylation COPA score > 5 and black = methylation COPA score > 10. CpGs have been hierarchically clustered using a Manhattan distance metric. Those mapping to PCGTs are labeled with their associated gene. Samples have been ordered according to their EVORA risk score as shown in the panels above heatmaps. (a) ARTISTIC cohort: 152 samples (75 prospective CIN2+ (red), 77 no CIN2+ at last follow-up (green). (b) Set 1: 48 samples (18 CIN2+ (red), 30 normals (green)). (c) Set 2: 63 cervical tissue samples (48 cancers (red), 15 normals (green)). (d) Heatmap depicts the same data matrix as in (c) but with the methylation values on the β-value scale where CpG β-values have been median normalized to zero. The corresponding scores now depict the percentage of methylation hits as measured on the beta-scale.