Characterization of the effect of drug combinations on KSHV reactivation.

Abstract

<p>(A) Distribution of the concentrations of the five drugs in the 50 drug combinations that lead to the highest KSHV reactivation rates simulated by the predictive reactivation model (blue bars). The drug concentration ranges in the optimal drug concentrations generated by the experiment-based cross entropy procedure are shaded in red. The bottom right figure shows a histogram of the reactivation rate of the top performing 50 samples. (B) Representative KSHV reactivation outputs for five-drug combinations. The results of the 1st (top graph) and 12th (middle graph) iterations in the first set of optimization iterations, and the 3rd (bottom graph) iteration in the second set of optimization iterations with smaller concentration ranges are shown. The x-axis represents the different drug combinations used in each iteration; the y-axis shows relative percentage of GFP-positive cells in the total cell population. The highest percentage of GFP-positive cells in individual iterations is set as 1.</p