In silico assessment on TdP risks of drug combinations under CiPA paradigm

Figure 1. Features (APD90, qNet, and CaD90) as a function of drug concentrations for hydroxychloroquine, diltiazem, and combined hydroxychloroquine-diltiazem. Panel (A) shows the result of APD90, panel (B) for qNet, and panel (C) for CaD90. The labels in \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mathrm{x}$$\end{document}x axis represent the concentration of each compound incorporated in the simulation. For example, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$3\times \mathrm{cmax}$$\end{document}3×cmax for the combination of compound A and B means that the concentration for each A and B is \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$3\times…

Figure 2. Distribution of qNet for 12 CiPA drugs (single drug effects). The qNet values shown in the figure were the average qNet values from drug concentration of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$1-4\times \mathrm{cmax}$$\end{document}1-4×cmax as in Li et al.39. The upper horizontal grey dashed line represents the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\mathrm{threshold}}_{1}=0.0652\mathrm{ \mu C}/\mathrm{\mu F}$$\end{document}threshold1=0.0652μC/μF and the lower one for \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\mathrm{threshold}}_{2}=0.0516\mathrm{ \mu C}/\mathrm{\mu F}$$\end{document}threshold2=0.0516μC/μF. The black…

Figure 3. The maps of TdP risk prediction. Panel 1 show the an example of detailed description of the combination maps. There are three unique combinations (blue boxes) that each contains various drug concentration pairs ranging from \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$0-4\times \mathrm{cmax}$$\end{document}0-4×cmax. Each blue box represents a map with a vertical and horizontal axis of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$0-4\times \mathrm{cmax}$$\end{document}0-4×cmax drug concentration variations. The axis value of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$0\times \mathrm{cmax}$$\end{document}0×cmax indicates the drug-free…

Figure 4. Bar chart of TdP risks of compounds from the combination of high, intermediate, and low-risk drugs. The horizontal axis represents the pairs of initial TdP risks of combined drugs, the vertical axis is the number of samples or compounds resulting from drug combinations, and the colored bars represent the predicted risk of compounds resulting from a combination of initial TdP risks of drugs. The value above each bar indicates number of samples of the corresponding bar.