Fig. 1: Clinical concordance of single-cell ex vivo drug profiling for glioblastoma.
a, Prospective multimodal profiling of a glioblastoma patient cohort (n = 27 patients) and diverse glioblastoma disease models. Patient numbers are indicated per data type. b, Percent of cells expressing each gene (y axis) per subpopulation (x axis; n = 22 patients; data points; shape indicates scRNA-seq dataset). P values were calculated by two-tailed Wilcoxon test. Box plots show 25th–75th percentiles with a line at the median; whiskers extend to 1.5 times the interquartile range. c, Inferred CNA analysis based on scRNA-seq datasets in b. Matched patient samples are connected by gray lines. Patients with less than 5% of cells with detected CNAs are excluded. d, Overview of the prospective cohort (n = 27 patients). See Supplementary Table 1 for full cohort information. conf., confidence. e, Real-time image-based ex vivo drug screening (PCY) workflow of glioblastoma patient samples. f, Example IF image of a glioblastoma patient sample (P040; scale bar, 60 µm). g, Baseline cellular composition across the prospective glioblastoma cohort measured by PCY. Underlines indicate patients with recurrent glioblastoma. h, GSD (rows; n = 3 drugs) response across patient samples (columns). GSD response is averaged across concentrations for TMZ and lomustine/carmustine (CCNU and BCNU, respectively). i,j, Stratification of newly diagnosed glioblastoma patient survival based on ex vivo TMZ sensitivity of (Nestin+/S100B+ and CD45−) cells (blue, TMZ sensitive; red, TMZ resistant). Kaplan–Meier survival curves are compared using the log-rank (Mantel–Cox) test, and the optimal TMZ PCY score cutpoint to stratify patients was determined by maximally selected rank statistics. i, PFS of the prospective glioblastoma cohort (n = 16 annotated patients) stratified by TMZ PCY score (100 µM). Tick mark indicates ongoing response. j, PFS (left) and OS (right) of the retrospective cohort (n = 18 patients) stratified by mean TMZ PCY score. k, TMZ PCY scores (dots; n = 34 patients across both cohorts) stratified by clinically reported median PFS7 to first-line TMZ chemoradiotherapy. Wilcoxon test. l, TMZ (50 µM) PCY scores across both cohorts (dots; n = 41 patients) stratified by MGMT promoter methylation status. Wilcoxon test. Box plots as in b. GBM, glioblastoma.
