MultiCTox: Empowering Accurate Cardiotoxicity Prediction through Adaptive Multimodal Learning
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
- Linlin Zhuo (ORCID: https://orcid.org/0000-0002-6586-0533)
- Xiangxiang Zeng (ORCID: https://orcid.org/0000-0001-6201-0114)
- Dongsheng Cao (ORCID: https://orcid.org/0000-0003-3604-3785)
- Xiaojun Yao (ORCID: https://orcid.org/0000-0001-9958-8438)
- Yuting Guo (ORCID: https://orcid.org/0000-0003-0220-9599)
- Yan Yang (ORCID: https://orcid.org/0000-0003-2289-0182)
- Lin Feng
- Zhenya Du
Institutions
- Central South University (CN)
- Wenzhou University (CN)
- Hunan University (CN)
- Faculty (United Kingdom) (GB)
- Anhui Xinhua University (CN)
- Guangzhou Xinhua University
- Wenzhou University of Technology
- Macao Polytechnic University (MO)
Publication Details
- Journal
- Journal of Chemical Information and Modeling
- Published
- 2025-03-27
- DOI
- https://doi.org/10.1021/acs.jcim.5c00022
- Citations
- 6
- Primary Topic
- Computational Drug Discovery Methods
- Type
- article
- Field-Weighted Citation Impact
- 9.03