Fig. 5. Methylation clustering reveals common immune response pathway activities with a subset of extra-cranial malignant rhabdoid tumours.

a DNA methylation clustering using non-negative matrix factorization (NMF) of paediatric chordoma data from this study (n = 2) and Hasselblatt et al.² (n = 23), atypical teratoid rhabdoid tumours (ATRT, n = 161) and extra-cranial rhabdoid tumours (MRT, n = 131). The respective ATRT subgroups identified in Johann et al.⁷⁴ and rhabdoid tumour (RT) subgroups identified in Chun et al¹⁷. are displayed in the track below. b Cophenetic coefficients (top) and silhouette widths (bottom) for NMF cluster solutions from k = 2 to k = 15. A robust clustering result was obtained at k = 5, with high cophenetic coefficient and silhouette width. c Uniform manifold approximation and projection (UMAP) clustering of RTs with chordomas. d Gene set enrichment analysis of genes with differentially methylated CpGs in paediatric chordoma compared to RT subgroups 1–3 and 5 using a logistic regression model corrected for the number of CpGs in the gene set using methylGSA⁷³. The number of genes associated with the gene ontology (GO) terms are shown and bars are coloured by FDR adjusted p values. The most significantly enriched terms, i.e. type I interferon, response to virus and type I interferon signalling pathway, had adjusted p values of 2.93e−08, 7.55e−08 and 1.13e−07, respectively.