Fig. 6: Convergence of LSD, genome-wide CRISPR activation and patients' datasets towards the discovery of cell-state-specific drivers.

a Schematic representation of the genome-scale CRISPR activation (CRISPRa) screens (partially assembled using BioRender.com). b Circular barplot depiction of the top single-guide RNAs (sgRNA) targets with a positive enrichment (median sgRNAs log2-fold-change (log2FC) >0.5, Rho Enrichment score <0.05 and gene expression in target cells CPM >5) in the indicated high-reporter expressing cells compared to the respective controls (color legend, n = 3 technical replica). Median sgRNA log2FC and Rho enrichment scores are represented by bars and dot size, respectively. c) Violin plot of the read-count distribution of sgRNA targets defined as connected to EMT terms by Ingenuity Pathway Analysis (n = 70). Data distribution is shown, with box indicating the interquartile range and inner line indicating the median. Whiskers extend to represent the data range, including outliers. P-values denote the significance of statistical comparisons by two-sided pairwise t-test. Scatter plot depicting The Cancer Genome Atlas (TCGA) GBM subtype-specific expression according to Verhaak et al.²¹ (d) or Garofano et al.²³ (e) classifications (X-axis) and GBM stem cells dependencies (Y-axis). Dot size represents gene expression values in naive IDH-wildtype hGICs. f, g Convergence of the indicated LSD-CRISPRa-screens data onto the GBM-state-expression dependencies plots in d and e. Dot size represents the median log2FC of the respective sgRNA targets. Note that top right/bottom left data highlight candidate GBM subtype-specific dependencies, with the top context-specific factors listed in the magnification. LSD logical synthetic cis-regulatory DNA, hGICs human glioma-initiating cells, EMT Epithelial-Mesenchymal-Transition. Source data are provided in the Source Data file.