Predicting Environmental Chemical Carcinogenicity using a Hybrid Machine-Learning Approach

ABSTRACT Determining environmental chemical carcinogenicity is an urgent need as humans are increasingly exposed to these chemicals. In this study, we determined the carcinogenicity of wide variety real-life exposure chemicals in large scale. To determine chemical carcinogenicity, we have developed carcinogenicity prediction models based on the hybrid neural network (HNN) architecture. In the HNN model, we included new SMILES feature representation method, by modifying our previous 3D array representation of 1D SMILES simulated by the convolutional neural network (CNN). We used 653 molecular descriptors modeled by feed forward neural network (FFNN), and SMILES as chemical features to train the models. We have developed three types of machine learning models: binary classification models to predict chemical is a carcinogenic or non-carcinogenic, multiclass classification models to predict severity of the chemical carcinogenicity, and regression models to predict median toxic dose of the chemicals. Along with the hybrid neural network (HNN) model that we developed, Random Forest (RF), Bootstrap Aggregating (Bagging) and Adaptive Boosting (AdaBoost) methods were also used for binary and multiclass classification. Regression models were developed using HNN, RF, Support Vector Regressor (SVR), Gradient Boosting (GB), Kernel Ridge (KR), Decision Tree with AdaBoost (DT), KNeighbors (KN), and a consensus method. For binary classification, our HNN model predicted with an average accuracy of 74.33% and an average AUC of 0.806, for multiclass classification, the HNN model predicted with an average accuracy of 50.58% and an average micro-AUC of 0.68, and for regression model, the consensus method achieved R 2 of 0.40. The predictive performance of our models based on a highly diverse chemicals is comparable to the literature reported models that included the similar and less diverse molecules. Our models can be used in identifying the potentially carcinogenic chemicals for a wide variety of chemical classes.