Comprehensive hepatotoxicity prediction: ensemble model integrating machine learning and deep learning
Muhammad Zafar Irshad Khan, Jia-Nan Ren, Cheng Cao, Hong-Yu-Xiang Ye, Hao Wang, Ya-Min Guo, Jinrong Yang, Jian‐Zhong Chen
Abstract
Background: Chemicals may lead to acute liver injuries, posing a serious threat to human health. Achieving the precise safety profile of a compound is challenging due to the complex and expensive testing procedures. In silico approaches will aid in identifying the potential risk of drug candidates in the initial stage of drug development and thus mitigating the developmental cost. Methods: In current studies, QSAR models were developed for hepatotoxicity predictions using the ensemble strategy to integrate machine learning (ML) and deep learning (DL) algorithms using various molecular features. A large dataset of 2588 chemicals and drugs was randomly divided into training (80%) and test (20%) sets, followed by the training of individual base models using diverse machine learning or deep learning based on three different kinds of descriptors and fingerprints. Feature selection approaches were employed to proceed with model optimizations based on the model performance. Hybrid ensemble approaches were further utilized to determine the method with the best performance. Results: The voting ensemble classifier emerged as the optimal model, achieving an excellent prediction accuracy of 80.26%, AUC of 82.84%, and recall of over 93% followed by bagging and stacking ensemble classifiers method. The model was further verified by an external test set, internal 10-fold cross-validation, and rigorous benchmark training, exhibiting much better reliability than the published models. Conclusion: The proposed ensemble model offers a dependable assessment with a good performance for the prediction regarding the risk of chemicals and drugs to induce liver damage.