Drug Repurposing Using Deep Embedded Clustering and Graph Neural Networks

Abstract

Drug repurposing has historically been an economically infeasible process for identifying novel uses for abandoned drugs. Modern machine learning has enabled the identification of complex biochemical intricacies in candidate drugs; however, many studies rely on simplified datasets with known drug-disease similarities. We propose a machine learning pipeline that uses unsupervised deep embedded clustering, combined with supervised graph neural network link prediction to identify new drug-disease links from multi-omic data. Unsupervised autoencoder and cluster training reduced the dimensionality of omic data into a compressed latent embedding. A total of 9,022 unique drugs were partitioned into 35 clusters with a mean silhouette score of 0.8550. Graph neural networks achieved strong statistical performance, with a prediction accuracy of 0.901, receiver operating characteristic area under the curve of 0.960, and F1-Score of 0.901. A ranked list comprised of 477 per-cluster link probabilities exceeding 99 percent was generated. This study could provide new drug-disease link prospects across unrelated disease domains, while advancing the understanding of machine learning in drug repurposing studies.