Journal
CHEMICAL BIOLOGY & DRUG DESIGN
Volume 98, Issue 2, Pages 248-257Publisher
WILEY
DOI: 10.1111/cbdd.13894
Keywords
consensus model; deep learning; drug-induced ototoxicity; machine learning; structural alert
Funding
- National Natural Science Foundation of China [81803433]
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The study focused on in silico modeling of drug-induced ototoxicity, collecting a large dataset to develop a series of computational models, which performed well in external validation with high accuracy.
Drug-induced ototoxicity has become a serious global problem, because of leading to deafness in hundreds of thousands of people every year. It always results from exposure to drugs or environmental chemicals that cause the impairment and degeneration of the inner ear. Herein, we focused on the in silico modeling of drug-induced ototoxicity of chemicals. We collected 1,102 ototoxic medications and 1,705 non-ototoxic drugs. Based on the data set, a series of computational models were developed with different traditional machine learning and deep learning algorithms implemented on an online chemical database and modeling environment. Six ML models performed best on 5-fold cross-validation and test set. A consensus model was developed with the best individual models. These models were further validated with an external validation. The consensus model showed best predictive ability, with high accuracy of 0.95 on test set and 0.90 on validation set. The consensus model and the data sets used for model development are available at . Besides, 16 structural alerts responsible for drug-induced ototoxicity were identified. We hope the results could provide meaningful knowledge and useful tools for ototoxicity evaluation in drug discovery and environmental risk assessment.
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