Integrating (deep) machine learning and cheminformatics for predicting human intestinal absorption of small molecules

Abstract

The oral route is the most preferred route for drug delivery, due to which the largest share of the pharmaceutical market is represented by oral drugs. Human intestinal absorption (HIA) is closely related to oral bioavailability making it an important factor in predicting drug absorption. In this study, we focus on predicting drug permeability at HIA as a marker for oral bioavailability. A set of 2648 compounds were collected from some early as well as recent works and curated to build a robust dataset. Five machine learning (ML) algorithms have been trained with a set of molecular descriptors of these compounds which have been selected after rigorous feature engineering. Additionally, two deep learning models - graph convolution neural network (GCNN) and graph attention network (GAT) based model were developed using the same set of compounds to exploit the predictability with automated extracted features. The numerical analyses show that out the five ML models, Random forest and LightGBM could predict with an accuracy of 87.71 % and 86.04 % on the test set and 81.43 % and 77.30 % with the external validation set respectively. Whereas with the GCNN and GAT based models, the final accuracy achieved was 77.69 % and 78.58 % on test set and 79.29 % and 79.42 % on the external validation set respectively. We believe deployment of these models for screening oral drugs can provide promising results and therefore deposited the dataset and models on the GitHub platform (https://github.com/hridoy69/HIA).