Topological regression as an interpretable and efficient tool for quantitative structure-activity relationship modeling

Abstract

Abstract Quantitative structure-activity relationship (QSAR) modeling is a powerful tool for drug discovery, yet the lack of interpretability of commonly used QSAR models hinders their application in molecular design. We propose a similarity-based regression framework, topological regression (TR), that offers a statistically grounded, computationally fast, and interpretable technique to predict drug responses. We compare the predictive performance of TR on 530 ChEMBL human target activity datasets against the predictive performance of deep-learning-based QSAR models. Our results suggest that our sparse TR model can achieve equal, if not better, performance than the deep learning-based QSAR models and provide better intuitive interpretation by extracting an approximate isometry between the chemical space of the drugs and their activity space.