Fig. 3
From: Personalized cancer therapy prioritization based on driver alteration co-occurrence patterns
Targeted Cancer Therapy for You (TCT4U), a collection of drug-response classifiers based on DCO networks. a Given a new tumor sample, we compare it to the patterns of driver alterations and co-alterations associated to response or lack of response to any of the treatments in TCT4U, and rank the drugs accordingly, predicting whether a drug will or not be effective. By quantifying each feature’s local contribution to individual predictions (SHAP values), we can know which are the precise molecular determinants used by the classifier and use this information for functional interpretation of the predictions. b Waterfall plot representing 3127 in vivo experiments, sorted left to right from the worst to the best response of 187 PDXs to 53 treatments. The heatmaps below show the predictions of TCT4U in a leave-one-out cross-validation setting, and the predictions made on the basis of approved or experimental biomarkers. Each heatmap has three rows, which correspond to the predictions obtained when examining the whole exome (WES), IMPACT410 (IM), or Foundation Medicine (FM) targeted gene panels. The number of predictions and the average balanced accuracy (BAcc) across treatments are annotated along the y-axis. The subset of high-confidence TCT4U predictions corresponds to the ones yielded by models that attained a BAcc of 0.6 or higher. The subset of high-confidence biomarkers corresponds to the subset of clinically approved ones. c Predictive performance of TCT4U-, biomarker-, and DCO + biomarker-based models, all trained with CatBoost within the TCT4U pipeline. d The precision of each set of predictions is illustrated by the red and blue sections of the stacked bar plots, which represent the proportion of correct response and non-response predictions. Analogously, incorrect predictions are represented in faint colors. Missing predictions (NA) are represented in white to offer a comparative overview of the recall. e Stacked bar plots representing the precision and recall of all TCT4U predictions and all previously known biomarkers covered by WES profiles split by treatment arm