Extended Data Fig. 2: Real-time neuroactive and oncology drug screening in samples from patients with glioblastoma. | Nature Medicine

Extended Data Fig. 2: Real-time neuroactive and oncology drug screening in samples from patients with glioblastoma.

From: High-throughput identification of repurposable neuroactive drugs with potent anti-glioblastoma activity

Extended Data Fig. 2

a, PCY score matrix of oncology drugs (ONCDs; columns; n = 65 drugs) across glioblastoma patient samples (rows; n = 12 patients). Heatmap color scale indicates the PCY score of glioblastoma cells (Nestin + /S100B+ and CD45-). Asterisks (*) denote FDR-adjusted P < 0.05 from a one-tailed t-test. b, PCY score matrix of neuroactive drugs (NADs, n = 67 drugs) averaged across glioblastoma patient samples (n = 27 patients) for each cell population defined by IF markers and total cell number (TCN). Heatmap color scale indicates the mean PCY score of each respective population averaged across patients. a, b, Outliers beyond color scale limits were correspondingly set to minimum and maximum values. For clinical and drug annotations, see Supplementary Tables 1 and 2. c-g Glioblastoma PCY scores (y-axis) plotted per patient against selected parameters (x-axis). c, Age versus Elesclomol response. Linear regression line with a 95% confidence interval. Pearson correlation coefficient with two-tailed P-value annotated. d, TP53 mutational status versus Abemaciclib response. e, RET mutational status versus Pazopanib response. f, Biological sex versus Brexpiprazole response. g, FGFR2 copy number loss versus Sertindole response. Conf: confidence. h, Example IF images of a patient sample (P025) at baseline (DMSO control) and treated with Vortioxetine. Scale bar, 60 µm. i-k, Comparison of neuroactive drug PCY scores of glioblastoma cells (n = 67 NADs; original PCY score) to NAD PCY scores calculated by excluding cleaved CASP3+ apoptotic cells. Apoptotic cells are defined either by IF (PCY score without IF CASP3 + ) or by the apoptotic CNN classifier (PCY score without CNN CASP3 + ; see also Methods). Pearson correlation coefficients with P-values annotated. i, j, NAD screens performed in two validation patient samples (P048, P049). i, Comparison of the original PCY score to the PCY score without IF CASP3+ j, Comparison of the PCY score without IF CASP3+ the PCY score without CNN CASP3+ k, Comparison of the original PCY score to the PCY score without CNN CASP3+ across the prospective cohort (n = 27 patients) and neuroactive drugs (n = 67 drugs). d-g, Two-tailed Wilcoxon test. Boxplots as in Fig. 1b.

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