MMDG-DTI: Drug–target interaction prediction via multimodal feature fusion and domain generalization

Abstract

Recently, deep learning has become the essential methodology for Drug–Target Interaction (DTI) prediction. However, the existing learning-based representation methods embed the prior knowledge encapsulated by the training data and, as such, acquire redundant domain information irrelevant to the DTI prediction, compromising the generalization capability of a deep network to unfamiliar instances. To tackle this limitation, we propose a novel DTI prediction method using Multi-Modal feature fusion and Domain Generalization (MMDG-DTI). Specifically, we first use pre-trained Large Language Models (LLMs) to obtain generalized textual features covering nearly the whole biological text vocabulary, with the capacity to handle unseen samples and extract robust and discriminative features. In parallel, we propose a unified structural feature extractor based on a hybrid Graph Neural Network (GNN). The extractor improves the performance of MMDG-DTI by extracting features from another modality and discarding the representation of domain-specific prior substructures. Then, we integrate the complementary information of LLM and GNN features using an innovative classifier, while enhancing the generalization ability with the help of Domain Adversarial Training (DAT) and contrastive learning. Last, we propose a novel cross-domain evaluation protocol to enhance the predication fidelity in practical applications. The quantitative and visualization results obtained on several benchmarking datasets demonstrate that MMDG-DTI achieves state-of-the-art performance under both single-domain and cross-domain settings, confirming the superiority of the proposed method. The datasets and codes will be available on the project homepage: https://github.com/JU-HuaY/MMDG-DTI.