Fig. 3

Validation of the MAPK/OIS/SASP molecules in primary pLGG samples. a Boxplot depicting the ssGSEA z-score of the OIS_UP or OIS_DN molecules (from RNAseq layer only, or all three omics layers combined) in 9 patient-derived pLGG models (ON = proliferating cells, OFF = senescent cells, BT40 = proliferating). b Boxplot depicting the signature score (z-score sum, arbitrary unit) of the OIS_UP molecules from the RNAseq, proteomics and phosphoproteomics layers in n = 6 pediatric glioma entities from the ProTrack Pediatric Brain Tumor dataset from Petralia et al. Each dot represents the median OIS_UP z-score of each tumor entity dataset indicated, for all three omics layers from supplementary (a–c). c Boxplot depicting the ssGSEA z-score of the OIS_UP genes from the RNAseq layer in n = 13 pediatric glioma entities from the Open Pediatric Brain Tumor Atlas. Dashed line depicts the overall median. MB medulloblastoma, EWS Ewin Sarcoma, EPN ependymoma, NB neuroblastoma, CNS other CNS embryonal tumor, ETMR embryonal tumor with multilayer rosettes, SEGA Subependymal Giant Cell Astrocytoma, CHDM chordoma, HGG high-grade glioma, CRANIO craniopharyngioma, GNT glial neuronal tumor, DMG diffuse midline glioma, pLGG low-grade glioma. d Boxplot depicting the ssGSEA z-score of the OIS_UP genes from the RNAseq layer in n = 10 pediatric low-grade glioma molecular subgroups from the Open Pediatric Brain Tumor Atlas. Dashed line depicts the overall median. Boxplots depict the median, first and third quartiles. Whiskers extend from the hinge to the largest/smallest value no further than 1.5 * IQR from the hinge (where IQR is the inter-quartile range). Significance was calculated with one-way ANOVA followed by the Tukey’s ‘Honest Significant Difference’ test. Depicted significance is in comparison to the group “MAPK wild type”, all other comparisons to other groups were not significant. e Kaplan–Meier curve of primary BRAF-driven PA samples from the ICGC PedBrain cohort grouped based on their enrichment for the OIS_UP genes from the RNAseq layer (p-value from log-rank test, and adjusted p-value corrected by Bonferroni method after multiple testing to identify the optimal cut-off with the best raw p-value). f Forest plot depicting the hazard ratio (HR) calculated in a univariate Cox proportional hazards model evaluating which clinico-molecular features are significantly associated with PFS. g Forest plot depicting the HR calculated in a multivariate Cox proportional hazards model evaluating independent prognostic factors