Fast polypharmacy side effect prediction using tensor factorization

Adverse reactions from drug combinations are increasingly common, making their accurate prediction a crucial challenge in modern medicine. Laboratory-based identification of these reactions is insufficient due to the combinatorial nature of the problem. While many computational approaches have been proposed, tensor factorization (TF) models have shown mixed results, necessitating a thorough investigation of their capabilities when properly optimized.

We demonstrate that TF models can achieve state-of-the-art performance on polypharmacy side effect prediction, with our best model (SimplE) achieving median scores of 0.978 area under receiver-operating characteristic curve, 0.971 area under precision-recall curve, and 1.000 AP@50 across 963 side effects. Notably, this model reaches 98.3% of its maximum performance after just two epochs of training (approximately 4 min), making it substantially faster than existing approaches while maintaining comparable accuracy. We also find that incorporating monopharmacy data as self-looping edges in the graph performs marginally better than using it to initialize embeddings.

All code used in the experiments is available in our GitHub repository (https://doi.org/10.5281/zenodo.10684402). The implementation was carried out using Python 3.8.12 with PyTorch 1.7.1, accelerated with CUDA 11.4 on NVIDIA GeForce RTX 2080 Ti GPUs.