Bridging the Modality Reliability Gap in Drug-Target Interaction Prediction via a Confidence-aware Multimodal Fusion Framework

Abstract

With the rapid advancement of deep learning, drug target interaction (DTI) prediction has seen substantial performance enhancements. However, existing methodologies face a critical, yet unaddressed challenge, i.e., the Modality Reliability Gap. Such a gap arises from the unpredictable variance in the informativeness and reliability of 1D sequence versus 3D structural data across different drug-target pairs, critically limiting model robustness and domain generalization capabilities. To overcome it, we introduce DrugCMF, a novel Drug-Target interaction prediction method via Confidence-aware Multimodal Fusion framework designed specifically to bridge the Modality Reliability Gap. Specifically, the DrugCMF employs a four-stage approach: (1) it extracts rich features by utilizing four pre-trained models to obtain token-level embeddings from both 1D sequences and 3D structures. (2) it preserves modality informativeness by independently learning interaction patterns within each modality through a Token-level Interaction module. (3) it explicitly quantifies the reliability gap by employing a novel confidence estimation mechanism to dynamically learn weights for each modality. (4) it bridges the gap by using these confidence scores to guide a learnable cross-modal fusion module, adaptively fusing information from the most trustworthy source. By methodically addressing the Modality Reliability Gap, DrugCMF significantly outperforms SOTA methods.