Figure 5. Subtype specific age acceleration in pediatric brain tumors assessed by Horvath methylation clock. (A) Age acceleration (Horvath methylation age minus chronological age) varies significantly (adj. p < 0.05) between all three ATRT subtypes in GSE90496 (n = 91; left panel), and the validation cohort (n = 49; right panel) shows the same trend with a significant difference (adj. p = 0.023) between the TYR and SHH subgroup. (B) In ependymoma (EPN), the YAP subgroup displays significantly lower age acceleration than the RELA (adj. p = 1.3e-6) and PF-A (adj. p = 1.0e-7) subgroups in GSE90496 (n = 157; left panel). Right panel with validation cohort (n = 65) shows significant difference between the RELA and PF_A subgroup (p = 0.02). (C) Left panel, GSE90496 (n = 295), is significantly different (adj. p < 0.05) for all pairs of gliomas except PXA (pleomorphic xanthoastrocytoma) vs LGG (low-grade glioma, mainly grade I) and K27 (diffuse midline glioma H3 K27M mutant), and GBM (glioblastoma) vs G34 (glioblastoma H3.3 G34 mutant). Middle panel with validation cohort (n = 153) varies significantly (adj. p < 0.05) between all pairs except K27 vs GBM and G34 and G34 vs GBM and DIPG, and right panel with local cohort (n = 86, p-value = 0.003). (D) The medulloblastoma (MB) subtypes in GSE90496 (n = 306; left panel) are significantly different for all pairs (adj. p < 1e-8) except SHH vs G4 (Group4). The age acceleration in the validation cohort (n = 48; middle panel) displays a similar trend in decreasing age acceleration, and in the local cohort (n=39; right panel) there is a significant difference between all pairs (adj. p < 0.05). Note that the subtypes in A-D have been ordered according to prognosis where the left-most subtype have the best prognosis and the right-most have the worst. Sample sizes for all included boxes is available in Supplementary Table 3.