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Fig. 2 | BMC Bioinformatics

Fig. 2

From: Statistical assessment and visualization of synergies for large-scale sparse drug combination datasets

Fig. 2

Heat maps of all pairwise drug combination results for cell line COLO792 low drug dose. a Viability (i.e. nuclei count divided by the average nuclei count in the DMSO treated wells) b-c Excess Over Bliss scores before (b) and after (c) linear modeling of the singlet viabilities (d) synergy Z values. In all heat maps rows and columns have the same order (sorted by singlet viabilities). Each heat map has a single row and single column of discs representing measured singlet viabilities (a-b) or estimated singlet viability by the Bliss linear model (c-d). Gray arrows indicate drugs where singlet viability was high compared with viabilities in combinations with other drugs, producing horizontal dark red rows in (a). This produces spuriously high Excess Over Bliss scores (b, gray arrows). Moreover, singlets with very high viability tend to produce a large number of high Excess Over Bliss scores even when the drug combination has no effect on the cells (a-b, top right corners). Such problems are not observed after the singlets are estimated from the linear model (c-d, top right corners and gray arrows) (e) Comparison between the solutions of the model (singlet viabilities) and the measured singlet viabilities (that were not used in the model). Error bars in the y axis indicate plus or minus 2 standard errors. Units of the model are shown: negative log10(1 + viability). f Model based on Bliss independence has a R squared of 0.90, indicating that it is a good model for the combination of drug effects. g Scatter plot of the singlet viabilities, experimentally measured versus estimated. The vertical error bars indicate the 95% confidence interval. h Scatter plot of combinations viabilities (measured versus estimated) for cell line 501MEL at high dose, the assay with the lowest R² in this dataset

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