Abstract：
The cardiotoxic effects of various pollutants have been a growing concern in environmental and material science. These effects encompass arrhythmias, myocardial injury, cardiac insufficiency, and pericardial inflammation. Compounds such as organic solvents and air pollutants disrupt the potassium, sodium, and calcium ion channels cardiac cell membranes, leading to the dysregulation of cardiac function. However, current cardiotoxicity models have disadvantages of incomplete data, ion channels, interpretability issues, and inability of toxic structure visualization. Herein, an interpretable deep-learning model known as CardioDPi was developed, which is capable of discriminating cardiotoxicity induced by the human Ether-à-go-go-related gene (hERG) channel, sodium channel (Na_v1.5), and calcium channel (Ca_v1.5) blockade. External validation yielded promising area under the ROC curve (AUC) values of 0.89, 0.89, and 0.94 for the hERG, Na_v1.5, and Ca_v1.5 channels, respectively. The CardioDPi can be freely accessed on the web server CardioDPipredictor (http://cardiodpi.sapredictor.cn/). Furthermore, the structural characteristics of cardiotoxic compounds were analyzed and structural alerts (SAs) can be extracted using the user-friendly CardioDPi-SAdetector web service (http://cardiosa.sapredictor.cn/). CardioDPi is a valuable tool for identifying cardiotoxic chemicals that are environmental and health risks. Moreover, the SA system provides essential insights for mode-of-action studies concerning cardiotoxic compounds.
摘要：
各种污染物的心脏毒性效应已成为环境和材料科学中日益关注的问题。这些影响包括心律失常，心肌损伤，心功能不全,和心包炎症.有机溶剂和空气污染物等化合物会破坏钾，钠,和钙离子通道心脏细胞膜，导致心脏功能失调.然而,目前的心脏毒性模型存在数据不完整的缺点，离子通道,可解释性问题，和无法进行毒性结构可视化。在这里，开发了一种称为CardioDPi的可解释深度学习模型，它能够区分由人Ether-à-go-go-go相关基因（hERG）通道诱导的心脏毒性，钠通道(Na_v1.5)，钙通道（Ca_v1.5）阻断。对于hERG，外部验证产生了有希望的ROC曲线下面积（AUC）值为0.89、0.89和0.94，Na_v1.5和Ca_v1.5通道，分别。CardioDPi可以在Web服务器CardioDPidornicator上自由访问（http://cardiodpi。Sapredictor.cn/)。此外，我们分析了心脏毒性化合物的结构特征,并使用用户友好的CardioDPi-SAdetector网络服务(http://cardiosa.Sapredictor.cn/)。CardioDPi是识别具有环境和健康风险的心脏毒性化学物质的有价值的工具。此外，SA系统为有关心脏毒性化合物的作用模式研究提供了必要的见解.
