Fig. 5: Pharmacological Validation of the Brunello CRISPR Knockout Screen.

a Drug screen of 127 FDA approved therapeutic agents in TP53-WT and TP53-KO background of F147T organoid, topoisomerase inhibitors are highlighted in red, and no drug controls are in blue. Circle sizes correlate with different drug concentrations. On the X-axis, a negative number means fewer total cells in the presence of drug compared to DMSO. On the Y-axis, a positive number means more TP53-WT cells than TP53-KO cells (or fewer TP53-KO cells compared to TP53-WT cells). b Sunburst chart of 34 out of 127 therapeutic agents by their maximal effect on TP53 status and their mechanism of action. c Validation effect of topoisomerase inhibitors Etoposide, Teniposide, Topotecan, and Daunorubicin that mainly affected TP53-KO organoids. Nutlin and Cisplatin showed expected effects on TP53-WT organoids shown in yellow and green respectively. Selected drugs are color-coded, and circle sizes correlate with different drug concentrations. On the X-axis, a negative number means fewer total cells in drug compared to DMSO. On the Y-axis, a positive number means more TP53-WT cells than TP53-KO cells (or less TP53-KO cells compared to TP53-WT cells).