Fig. 3: RNA-Seq data supports Hh signaling activation in meningiomas acquiring SVs on 2q35 and 7q36.3.

a Clustering of meningiomas based on RNA-Seq data is presented using t-distributed stochastic neighbor embedding (t-SNE) of the first five eigenvectors obtained from spectral clustering. Each sample is represented by a number (for cluster membership) and color (for underlying driver event). A curve that encloses the samples belonging to the cluster 1 (named as Hh cluster) is drawn for illustration purposes. b A volcano plot of the differential expression (DE) tests for the Hh cluster against other meningiomas is shown. Red points show DE genes in the gene co-expression module M5 (n = 112). The top 20 genes ranked by s-values based on the local false sign rate (s_LFSR) are labeled. Volcano plots for other clusters are presented in Supplementary Fig. 6. c Module eigengene distribution across transcriptional clusters for the module M5 is shown. Only the Hh cluster showed significant association with M5 (linear regression using 42 biologically independent samples, Benjamini-Hochberg corrected P-value = 1.2 × 10⁻¹⁴, Supplementary Fig. 7 and Supplementary Data 14). A boxplot indicates median (middle line), the first (Q1) and the third (Q3) quartiles (box), the smallest value down to Q1–1.5 IQR and the largest value up to Q3 + 1.5 IQR (whiskers), where IQR = Q3–Q1. Values beyond the end of the whiskers are plotted individually (outliers). Points are jittered horizontally to avoid overlaps. d Size factor-normalized read counts⁷⁶ are plotted against meningioma driver subgroups for IHH and SSH. Expression of IHH and SHH were elevated among samples with SVs on 2q and 7q, respectively. On top of each panel, s_LFSR and posterior log2 fold change (postLFC) from DE analysis (Hh vs. others) are shown. TD, tandem duplication. CTX, inter-chromosomal translocation. CNV, copy number variation. CT, chromothripsis. Source data are provided as a Source Data file.