Identification of compounds that selectively kill cancer cells with high CA20.

(a) Compounds with selective activity on cell lines with high or low CA20 score. The volcano plot shows the results of Spearman’s correlation analyses between CA20 scores and compound Area Under the dose-response Curve (AUC) across Cancer Therapeutics Response Portal (CTRP) human cancer cell lines. Note that lower AUC means higher drug activity. The compounds whose activity was associated with high and low CA20 (FDR b) Top 6 compounds targeting cells with higher CA20 score. Smooth scatter plots showing correlation between CA20 score and compound AUC across CTRP cell lines for the top 6 compounds from (a). Spearman’s correlation coefficients, r, and respective p-values are shown. (c) Compounds that down-regulate the CA20 gene set. Heatmap of CMap’s drug score, ranging from 100 (maximum CA20 up-regulation) to -100 (maximum CA20 down-regulation) per cell line. Drug average score (last column) is the mean of drug scores across cell lines. The 20 compounds with the lowest drug average score are shown and ranked accordingly. Tissue of origin of human cancer cell lines: PC3: prostate; VCAP: prostate; A375: melanoma; A549: lung; HA1E: kidney; HCC515: lung; HT29: colon; MCF7: breast; HEPG2: liver. (d) Compounds selectively targeting cells with higher CA20 also down-regulate these genes. Scatter plot showing correlation between CTRP’s Spearman’s correlation coefficient from (a) and CMap’s drug average score from (c) for the 164 compounds tested in both datasets (Spearman’s correlation coefficient, r = 0.26, p-value = 8.3e-4). Points are coloured as in (a) and the predicted protein targets of compounds with both significant Spearman’s correlations and drug average score lower than -90 are shown.