CardiOT: Towards Interpretable Drug Cardiotoxicity Prediction Using Optimal Transport and Kolmogorov--Arnold Networks

文献类型： 外文期刊

第一作者： Zhang, Xinyu

作者： Zhang, Xinyu;Zhuo, Linlin;Wang, Hao;Du, Zhenya;Fu, Xiangzheng;Cao, Dongsheng;Xie, Boqia;Li, Keqin

作者机构：

关键词： Drugs; Compounds; Predictive models; Ions; Chemicals; Safety; Data models; Accuracy; Toxicology; Prediction algorithms; Cardiac drug safety; compound cardiotoxicity (CCT); inhibitory effects of drugs; Kolmogorov--Arnold networks (KANs); optimal transport (OT); uneven distribution and data scarcity

期刊名称：IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS （ 影响因子：6.8； 五年影响因子：7.0 ）

ISSN： 2168-2194

年卷期： 2025 年 29 卷 3 期

页码：

收录情况： SCI

摘要： Investigating the inhibitory effects of compounds on cardiac ion channels is essential for assessing cardiac drug safety. Consequently, researchers have developed computational models to evaluate combined cardiotoxicity (CCT) on cardiac ion channels. However, limitations in experimental data often cause issues like uneven data distribution and scarcity. Additionally, existing models primarily emphasize atomic information flow within graph neural networks (GNNs) while overlooking chemical bonds, leading to inadequate recognition of key structures. Therefore, this study integrates optimal transport (OT), structure remapping (SR), and Kolmogorov-Arnold networks (KANs) into a GNN-based CCT prediction model, CardiOT. First, the proposed CardiOT model employs OT pooling to optimize sample-feature joint distribution using expectation maximization, identifying "important" sample-feature pairs. Additionally, SR technology is used to emphasize the role of chemical bond information in message propagation. KAN technology is integrated to greatly enhance model interpretability. In summary, the model mitigates challenges related to uneven data distribution and scarcity. Multiple experiments on public datasets confirm the model's robust performance. We anticipate that this model will provide deeper insights into compound inhibition mechanisms on cardiac ion channels and reduce toxicity risks.

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