Reusability report: exploring the utility of variational graph encoders for predicting molecular toxicity in drug design

Variational graph encoders effectively combine graph convolutional networks with variational autoencoders, and have been widely employed for biomedical graph-structured data. Lam and colleagues developed a framework based on the variational graph encoder, NYAN, to facilitate the prediction of molecular properties in computer-assisted drug design. In NYAN, the low-dimensional latent variables derived from the variational graph autoencoder are leveraged as a universal molecular representation, yielding remarkable performance and versatility throughout the drug discovery process. In this study we assess the reusability of NYAN and investigate its applicability within the context of specific chemical toxicity prediction. The prediction accuracy—based on NYAN latent representations and other popular molecular feature representations—is benchmarked across a broad spectrum of toxicity datasets, and the adaptation of NYAN latent representation to other surrogate models is also explored. NYAN, equipped with common surrogate models, shows competitive or better performance in toxicity prediction compared with other state-of-the-art molecular property prediction methods. We also devise a multi-task learning strategy with feature enhancement and consensus inference by leveraging the low dimensionality and feature diversity of NYAN latent space, further boosting the multi-endpoint acute toxicity estimation. The analysis delves into the adaptability of the generic graph variational model, showcasing its aptitude for tailored tasks within the realm of drug discovery.