Machine learning based dynamic consensus model for predicting blood-brain barrier permeability

Abstract

The blood-brain barrier (BBB) is an important defence mechanism that restricts disease-causing pathogens and toxins to enter the brain from the bloodstream. In recent years, many in silico methods were proposed for predicting BBB permeability, however, the reliability of these models is questionable due to the smaller and class-imbalance dataset which subsequently leads to a very high false positive rate. In this study, machine learning and deep learning-based predictive models were built using XGboost, Random Forest, Extra-tree classifiers and deep neural network. A dataset of 8153 compounds comprising both the BBB permeable and BBB non-permeable was curated and subjected to calculations of molecular descriptors and fingerprints for generating the features for machine learning and deep learning models. Three balancing techniques were then applied to the dataset to address the class-imbalance issue. A comprehensive comparison among the models showed that the deep neural network model generated on the balanced MACCS fingerprint dataset outperformed with an accuracy of 97.8% and a ROC-AUC score of 0.98 among all the models. Additionally, a dynamic consensus model was prepared with the machine learning models and validated with a benchmark dataset for predicting BBB permeability with higher confidence scores.