TCN-RDP: Predicting Drug-Induced Liver Injury from Time-Series Toxicogenomic Data
Drug-induced liver injury (DILI) is a major obstacle in drug development, often leading to high failure rates in clinical trials. Traditional toxicological assessments are slow and resource-intensive, making early prediction of hepatotoxicity a significant challenge. To address this, we propose TCN-RDP, a novel model that integrates Temporal Convolutional Networks (TCN) and Random Dimension Permutation (RDP). TCN captures temporal dependencies in gene expression data, while RDP enhances the modeling of high-dimensional gene interactions, allowing for better feature representation. Additionally, an XGBoost-based gene selection algorithm improves the model's interpretability by focusing on the most relevant genes. In comparison to conventional methods, TCN-RDP achieved a significant accuracy of 84.05%. This model provides a biologically interpretable framework for early stage hepatotoxicity prediction, offering a more efficient and precise approach to drug safety assessment. Future work aims to extend the model to human-derived data and further refine toxicity stratification, enhancing its potential for regulatory decision-making and early drug screening.
Authors
- Jie Geng (ORCID: https://orcid.org/0000-0003-4858-823X)
- Leyi Wei (ORCID: https://orcid.org/0000-0003-1444-190X)
- Changming Sun (ORCID: https://orcid.org/0000-0001-5943-1989)
- Ran Su
- Ruibing Chen (ORCID: https://orcid.org/0000-0002-1149-8049)
- Mingxiao Lang
- Bin Li (ORCID: https://orcid.org/0000-0002-8979-610X)
- Rui Deng (ORCID: https://orcid.org/0000-0002-0856-0796)
- Haochen Zuo
- Zhong‐Yan Zhao
Institutions
- Commonwealth Scientific and Industrial Research Organisation (AU)
- Tianjin University of Science and Technology (CN)
- Tianjin University of Technology (CN)
- Tianjin University (CN)
- Tianjin Medical University Cancer Institute and Hospital (CN)
- London Chest Hospital (GB)
- Chest Diseases Hospital (KW)
- Centre for Artificial Intelligence and Robotics (IN)
- Tianjin Chest Hospital (CN)
- Data61 (AU)
- Macao Polytechnic University (MO)
Publication Details
- Journal
- Journal of Chemical Information and Modeling
- Published
- 2025-10-07
- DOI
- https://doi.org/10.1021/acs.jcim.5c01678
- Primary Topic
- Computational Drug Discovery Methods
- Type
- article
- Field-Weighted Citation Impact
- 0.00