PolyLLM: polypharmacy side effect prediction via LLM-based SMILES encodings

Polypharmacy, the concurrent use of multiple drugs, is a common approach to treating patients with complex diseases or multiple conditions. Although consuming a combination of drugs can be beneficial in some cases, it can lead to unintended drug-drug interactions (DDI) and increase the risk of adverse side effects. Predicting these adverse side effects using state-of-the-art models like Large Language Models (LLMs) can greatly assist clinicians. In this study, we assess the impact of using different LLMs to predict polypharmacy. First, the chemical structure of drugs is vectorized using several LLMs such as ChemBERTa, GPT, etc., and are then combined to obtain a single representation for each drug pair. The drug pair representation is then fed into two separate models including a Multilayer Perceptron (MLP) and a Graph Neural Network (GNN) to predict the side effects. Our experimental evaluations show that integrating the embeddings of Deepchem ChemBERTa with the GNN architecture yields more effective results than other methods. Additionally, we demonstrated that utilizing complex models like LLMs to predict polypharmacy side effects using only chemical structures of drugs can be highly effective, even without incorporating other entities such as proteins or cell lines, which is particularly advantageous in scenarios where these entities are not available.