Experimental validation of the model predictions on the MDA-MB-231 cell line.

<p>(<b>A</b>) Distributions of cell growth inhibition percentages in single and pairwise siRNA screens targeting different groups of kinase targets. TIMMA identified eight target nodes, with a total of 20 kinase targets, the essentiality of which was evaluated both individually (n = 18) as well as in combination (n = 153) in the siRNA screens. Kinase target pairs with the predicted efficacy values higher or lower than the average (0.594) were further classified as high or low sensitivity groups, respectively. The kinome-wide single siRNA screen included a total of 704 kinases as a background reference distribution. (<b>B</b>) Scatterplot of synergy scores derived from the TIMMA model prediction versus synergy scores derived from the pairwise siRNA screen for a total of 68 drug pairs. A jitter function was applied for distinguishing the different drug pairs having the same synergy scores. The red dashed line indicates an empirical cut-off of predicted synergy score of 0.36 for the classification of highly synergistic drug pairs, for which the corresponding siRNA-measured synergy scores are higher than 37% (green dashed line). The blue curve is the logistic growth function fit where <i>a</i> = 41, <i>b</i> = 0.23, <i>c</i> = 0.02.