Predictive binary mixture toxicity modeling of fluoroquinolones (FQs) and the projection of toxicity of hypothetical binary FQ mixtures: a combination of 2D-QSAR and machine-learning approaches
Mainak Chatterjee, Kunal Roy
Abstract
(endpoint: log 1/IC50 in molar) have been utilized. We have used only 0D-2D descriptors to efficiently encode the structural features of mixture components without any additional complexities. The optimization of the class of mixture descriptors has been performed in this study by using three different mixing rules (linear combination of molecular contributions, the squared molecular contributions, and the norm of molecular contributions). Different machine-learning approaches namely, random forest (RF), ada boost, gradient boost (GB), extreme gradient boost (XGB), support vector machine (SVM), linear support vector machine (LSVM), and ridge regression (RR) have been employed here apart from the conventional partial least squares (PLS) regression to optimize the modeling approach. A rigorous validation protocol has been used for assessing the goodness-of-fit, robustness, and external predictability of the models. Finally, the toxicity of possible untested mixtures of different photodegradation products of fluoroquinolones has been predicted using the best model reported in this study.