a. Drug responses for Panobinostat (green) and PLX4720 (orange/purple) represented by the high-concentration effect level (Amax) and transitional concentration (EC50) for a sigmoidal fit to the response curve (b). c. Elastic net regression modeling of genomic features that predict sensitivity to PD-0325901. The bottom curve indicates drug response, measured as the area over the dose-response curve (activity area), for each cell line. The central heatmap shows the CCLE features in the model (continuous z-score for expression and copy-number, dark red for discrete mutation calls), across all cell lines (x-axis). Bar plot (left): weight of the top predictive features for sensitivity (bottom) or insensitivity (top). Parenthesis indicate features present in >80% of models after bootstrapping. d. Specificity and sensitivity (ROC curves) of cross-validated categorical models predicting the response to a MEK inhibitor, PD-0325901 (activity area). Mean true positive rate and standard deviation (n=5) are shown when models are built using all lines (“Global categorical model” in blue and orange), or within only melanoma lines (green). e. Activity area values for LBH589 (panobinostat) between cell lines derived from hematopoietic (n=61) and solid tumors (n=387). The middle bar = median, box = inter-quartile range, and bars extend to 1.5x the inter-quartile range. f. Distribution of activity area values for AEW541 relative to IGF1 mRNA expression. Orange dots: multiple myeloma cell lines (n=14); blue dots: cell lines from other tumor types (n=434). Box-and-whisker plots show the activity area or mRNA expression distributions relative to each cell line type (line = median and box = inter-quartile range), with bars extending to 1.5x the inter-quartile range.