Fig. 4: The integration of a bulk-derived transcriptional response signature for the OLIG2 inhibitor CT-179 predicts targeting of OPC-like GBM cells.

a Diagram of workflow for identifying CT-179 combinations using scFOCAL and cell-drug connectivity. b Heatmap of GBM8 cells treated with vehicle or 200 nM CT-179 for 24 h. Columns represent biological replicates. c Bar plot depicting the proportion of tumor cells within each patient tumor predicted to be sensitive (CT-179 response ρ < 0) or resistant (CT-179 response ρ > 0) to CT-179 treatment. d. Hierarchy plot of GBM tumor cells arranged by their relative expression of Neftel et al. states colored by predicted sensitivity or resistance to CT-179 treatment. e Violin and box plot of GBM cell CT-179 connectivity (ρ) grouped by assigned GBM cell transcriptional state (Kruskal–Wallis p < 2.2 × 10−16; For all pairwise comparisons, unpaired two-sided Wilcoxon signed-rank test with Benjamini–Hochberg correction p.adj <2.2 × 10−16). The center line of each box represents the median, box limits represent the first and third quartiles, and whiskers extend to the minimum and maximum data points. The violin outline indicates the kernel density of single-cell connectivity values. Data represents 53,542 single tumor cells aggregated across 11 individual patient samples. Source data are provided as a Source Data file.