Figure 1
From: Distinct methylation profiles characterize fusion-positive and fusion-negative rhabdomyosarcoma
Unsupervised analyses of methylation profiles distinguish fusion-positive from fusion-negative rhabdomyosarcoma. (a) Unsupervised hierarchical clustering of methylation profiles from 37 rhabdomyosarcoma tumors. Pearson's correlation and ward linkage were applied to the top 10% of probes with greatest variation (based on standard deviation) in the clustering analysis. Each column represents an individual sample with the 20 fusion-positive rhabdomyosarcoma cases shown as red rectangles and the 17 fusion-negative rhabdomyosarcoma cases shown as blue rectangles above the heat map. The blue and red lines in the heat map indicate low and high methylation levels according to the scale below the heat map. (b) Principal component analysis of rhabdomyosarcoma tumor methylation data. 20 fusion-positive (red dots) and 17 fusion-negative (blue dots) rhabdomyosarcoma cases were clustered with the 10% of probes with greatest sample-to-sample variation (based on standard deviation). (c) Unsupervised hierarchical clustering of DNA methylation profiles from rhabdomyosarcoma cell lines. Clustering of the cases was based on the top 1000 probes with the greatest sample-to-sample variability in methylation across the 10 rhabdomyosarcoma cell lines. In the dendrogram, each cell line is shown in one column, with the fusion-positive rhabdomyosarcoma lines indicated by red rectangles and fusion-negative rhabdomyosarcoma lines indicated by blue rectangles above the heat map. (d) Distribution of DNA methylation (β) levels. The most variable (top 10%) CpG sites were examined in 20 fusion-positive (red) and 17 fusion-negative (blue) rhabdomyosarcoma tumors. The y axis corresponds to frequency of a methylation level (expressed as β) such that the total probability (area under curve) is equal to one. Density plots for β-values were computed with the density function (kernel density estimation with a Gaussian smoothing function). (e) Comparison of overall methylation levels. The methylation levels of the top 10% of probes with greatest variation (based on standard deviation) are depicted by standardized average methylation levels across the genome in the 20 fusion-positive (red) and 17 fusion-negative (blue) samples. FN, fusion-negative rhabdomyosarcoma; FP, fusion-positive rhabdomyosarcoma.
