Fig. 5: An scFOCAL combination index predicts synergistic combination of an OLIG2 inhibitor CT-179 with Depatux-M (ABT-414), an anti-EGFR antibody MMAF drug conjugate.

a Volcano plot depicting results from limma-based differential drug connectivity between predicted CT-179 sensitive and resistant GBM cells. Patient ID was used as a covariate in the model design. b Bar plot of L1000 small molecule mean resistant cell connectivity (RCC) to predicted CT-179 resistant cells. Color depicts this same value. c Scatterplot of L1000 small molecules plotted by resistant vs. sensitive differential connectivity and mean CT-179 resistant cell connectivity. Colors depict the calculated scFOCAL combination index, the product of multiplying the differential connectivity log₂FC values by mean CT-179 resistant cell connectivity values for each individual molecule. Compounds highlighted in (a–c) are varlitinib, an EGFR inhibitor, and indibulin and docetaxel, which act through inhibition of tubulin. d Bioluminescence signal quantification of GBM6-eGFP-FLUC2 orthotopic xenograft tumors (means \(\pm \,\)SD, Combo vs Vehicle: p.adj <0.005 from Day 14, Combo vs. CT-179 monotherapy: p.adj <0.05 from Day 11, Adjusted p-values from multiple t-tests (two-sided) with Holm–Šídák correction to control the family-wise error rate). e Kaplan–Meier survival curves of mice bearing GBM6-eGFP-FLUC2 orthotopic xenografts treated with indicated therapies (n = 10 per group). MS: median survival. P-values determined using Log-rank (Mantel-Cox) test. Source data are provided as a Source Data file.