Development of classification models for predicting inhibition of mitochondrial fusion and fission using machine learning methods.
Journal:
Chemosphere
Published Date:
Oct 9, 2020
Abstract
Mitochondrial fusion and fission are processes to maintain mitochondrial function when cells respond to environment stresses. Disruption of mitochondrial fusion and fission influences cell health and can cause adverse events such as neurodegenerative disorders. It is critical to identify environmental chemicals that can disrupt mitochondrial fusion and fission. However, experimentally testing all the chemicals is not practical because experimental methods are time-consuming and costly. Quantitative structure-activity relationship (QSAR) modeling is an attractive approach for evaluation of chemicals disrupting potential on mitochondrial fusion and fission. In this study, QSAR models were developed for differentiating chemicals capable of inhibition of mitochondrial fusion and fission using machine learning algorithms (i.e. random forest, logistic regression, Bernoulli naive Bayes, and deep neural network). One hundred iterations of five-fold cross validations and external validations showed that the best model on mitochondrial fusion had area under the receiver operating characteristic curve (AUC) of 82.8% and 78.1%, respectively; and the best model for mitochondrial fission yielded AUC of 84.3% and 97.5%, respectively. Furthermore, 45 and 56 structural alerts were identified for inhibition of mitochondrial fusion and fission, respectively. The results demonstrated that the models and the structural alerts could be useful for screening chemicals that inhibit mitochondrial fusion and fission.
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