LLM-Enhanced Multimodal Framework for Drug–Drug Interaction Prediction
Song Im, Younhee Ko · Biomedicines · 2025
Background: Drug–drug interactions (DDIs) involve pharmacokinetic or pharmacodynamic changes that occur when multiple drugs are co-administered, potentially leading to reduced efficacy or adverse effects. As polypharmacy becomes more prevalent, especially among patients with chronic diseases, scalable and accurate DDI prediction has become increasingly important. Although numerous computational approaches have been proposed to predict DDIs using various modalities such as chemical structure and biological networks, the intrinsic heterogeneity of these data complicates unified modeling; Methods: We address this challenge with a multimodal deep learning framework that integrates three complementary, heterogeneous modalities: (i) chemical structure, (ii) BioBERT-derived semantic embeddings (a domain-specific large language model, LLM), and (iii) pharmacological mechanisms through the CTET proteins. To incorporate indirect biological pathways within the PPI network, we apply a random walk with restart (RWR) algorithm. Results: Across features combinations, fusing structural feature with BioBERT embedding achieved the highest classification accuracy (0.9655), highlighting the value of readily available data and the capacity of domain-specific language models to encode pharmacological semantics from unstructured texts. Conclusions: BioBERT embeddings were particularly informative, capturing subtle pharmacological relationships between drugs and improving prediction of potential DDIs. Beyond predictive performance, the framework is readily applicable to real-world clinical workflows, providing rapid DDI references to support the polypharmacy decision-making.