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.

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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
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article

TCN-RDP: Predicting Drug-Induced Liver Injury from Time-Series Toxicogenomic Data

Jie Geng, Leyi Wei, Changming Sun, Ran Su et al.
Journal of Chemical Information and Modeling
Computational Drug Discovery Methods
article

TCN-RDP: Predicting Drug-Induced Liver Injury from Time-Series Toxicogenomic Data

Jie Geng, Leyi Wei, Changming Sun, Ran Su, Ruibing Chen, Mingxiao Lang, Bin Li, Rui Deng, Haochen Zuo, Zhong‐Yan Zhao
article en

Abstract

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.

Journal of Chemical Information and ModelingVol. 65(20)
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)
Openalex Percentile: Top 71%
Computational Drug Discovery Methods
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