Extended Data Fig. 6: Correlation of Predicted and Observed Viability in Monotherapies and Combination Treatments in Cell Lines.

Each scatter plot compares experimental cell viability (N = 20, x-axis; scaled per drug treatment) with predicted viability (N = 20, y-axis; rescaled AUC value). Points represent patient-derived cell line responses, color-coded by line and shape-coded by drug. Pearson correlation (R) is noted in each plot’s lower right corner. All panels feature error bands showing the 95% confidence interval of the fit. A) Monotherapy Response at Median IC50: Relation between monotherapy response and experimental response (N = 20 each). B) Combination Therapy Response at Median IC50: Similar analysis for combination therapy (N = 15 each). C) Monotherapy Response at 3x Median IC50: Examines monotherapy response at higher concentration (N = 20 each). D) Combination Therapy at 3x Median IC50: Analyzes combination therapy response at increased concentration (N = 15 each). E-G) Monotherapy and Combination Response Prediction in Lung Cancer Cell Lines: E) UMAP Clustering: Represents 53,514 cells from 199 cell lines (~300 cells/line) using sc-expression, identifying 29 clusters with cells from four unique sub-clones. F-G) Predicted Viability Based on Most-Resistant Clone: Viability predictions for 21 lung cancer cell lines (N = 11 resistant & 10 sensitive cell ines), considering the most resistant clone. Statistical significance assessed with two-sided Wilcoxon rank-sum test. H-I) Monotherapy and Combination Response Prediction in Patient-Derived HNSC Primary Cells (N = 5): H) Monotherapy Response Based on Most-Resistant Clone: Presents PERCEPTION predicted viability and resistance vs. sensitivity stratification (N = 2 resistant & 3 sensitive). Includes drugs docetaxel, epothilone-b, gefitinib, and vorinostat. I) Combination Response: Similar analysis for combination treatments. Both panels include a left-side plot for predicted viability in resistant (N = 2) vs. sensitive (N = 3) lines and a right-side ROC plot showing prediction power (sensitivity and specificity). AUC values are provided, with the dashed line indicating random-model performance. Statistical analysis performed with two-sided Wilcoxon rank-sum test. All box plots depict median, 25th/75th percentiles, and range.