Deep Learning Prediction of Drug-Induced Liver Toxicity by Manifold Embedding of Quantum Information of Drug Molecules.

Abstract

Purpose: Drug-induced liver injury, or DILI, affects numerous patients and also presents significant challenges in drug development. It has been attempted to predict DILI of a chemical by in silico approaches, including data-driven machine learning models. Herein, we report a recent DILI deep-learning effort that utilized our molecular representation concept by manifold embedding electronic attributes on a molecular surface.

Methods: Local electronic attributes on a molecular surface were mapped to a lower-dimensional embedding of the surface manifold. Such an embedding was featurized in a matrix form and used in a deep-learning model as molecular input. The model was trained by a well-curated dataset and tested through cross-validations.

Results: Our DILI prediction yielded superior results to the literature-reported efforts, suggesting that manifold embedding of electronic quantities on a molecular surface enables machine learning of molecular properties, including DILI.

Conclusions: The concept encodes the quantum information of a molecule that governs intermolecular interactions, potentially facilitating the deep-learning model development and training.