External validation in TCGA data. (A) Standard deviation of probes overlapping UC DMRs and those that are outside of UC DMRs. (B) Differences in mean methylation levels between tumors and adjacent histologically normal tissue stratified by methylation patterns. (C) Heatmap of co-clustering frequencies of tumors derived by K-means consensus clustering of the 2,000 most variable probes in the TCGA data. (D) Tumor subgroupings derived using K-means clustering on the 25% most varying DMR-overlapping probes or the 2,000 most variable probes. (E) Hierarchical clustering of probes and heat map visualization of the three methylation clusters. The plot shows four main clusters of differentially methylated probes (leftmost annotation bar) and the associated chromatin states in H1ESC (middle bar, states as in Figure 1). The average methylation level in adjacent normal bladder tissue is indicated in the rightmost bar.