MultiCTox: Empowering Accurate Cardiotoxicity Prediction through Adaptive Multimodal Learning.

Journal: Journal of chemical information and modeling
PMID:

Abstract

Cardiotoxicity refers to the inhibitory effects of drugs on cardiac ion channels. Accurate prediction of cardiotoxicity is crucial yet challenging, as it directly impacts the evaluation of cardiac drug efficacy and safety. Numerous methods have been developed to predict cardiotoxicity, yet their performance remains limited. A key limitation is that these methods often rely solely on single-modal data, making multimodal data integration challenging. As a result, we present a multimodal method integrating molecular SMILES, structure, and fingerprint to enhance cardiotoxicity prediction. First, we designed a fusion layer to unify representations from different modalities. During training, the model maximizes intramodal similarity for the same molecule while minimizing intermolecular similarity, ensuring consistent cross-modal representations. This study evaluates the inhibitory effects of candidate drugs on voltage-gated potassium (hERG), sodium (Nav1.5), and calcium (Cav1.2) channels. Experimental results demonstrate that the proposed model significantly outperforms existing state-of-the-art methods in cardiotoxicity prediction. We anticipate that this model will contribute significantly to the development and safety evaluation of cardiac drugs, reducing cardiotoxicity-related risks.

Authors

  • Lin Feng
    Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory of Animal Disease-Resistance Nutrition, Ministry of Education, Ministry of Agriculture and Rural Affairs, Key Laboratory of Sichuan Province, Sichuan 611130, China.
  • Xiangzheng Fu
  • Zhenya Du
    Guangzhou Xinhua University, 510520, Guangzhou, China.
  • Yuting Guo
    State Key Laboratory of Virtual Reality Technology and Systems, Beihang University, Beijing, China.
  • Linlin Zhuo
    School of Data Science and Artificial Intelligence, Wenzhou University of Technology, Wenzhou, Zhejiang 325035, China; College of Computer Science and Electronic Engineering, Hunan University, Changsha 410082, China.
  • Yan Yang
    Department of Endocrinology and Metabolism, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
  • Dongsheng Cao
    School of Pharmaceutical Sciences, Central South University, Changsha, China. oriental-cds@163.com.
  • Xiaojun Yao
    Centre for Artificial Intelligence Driven Drug Discovery, Faculty of Applied Sciences, Macao Polytechnic University, Macao, 999078, PR China.