Multi-View Fused Nonnegative Matrix Completion Methods for Drug-Target Interaction Prediction.

Abstract

Accurate prediction of drug-target interactions (DTIs) is crucial for accelerating drug discovery and reducing experimental costs. However, challenges such as sparse interactions and heterogeneous datasets complicate this prediction. In this study, we hypothesize that leveraging nonnegative matrix completion and integrating heterogeneous similarity information from multiple biological views can improve the accuracy, interpretability, and scalability of DTI prediction. To validate this, we propose two multi-view fused nonnegative matrix completion methods that combine three key components: (1) a nonnegative matrix completion framework that avoids heuristic rank selection and ensures biologically interpretable predictions; (2) a linear multi-view fusion mechanism, where weights over multiple drug and target similarity matrices are jointly learned through linearly constrained quadratic programming; and (3) multi-graph Laplacian regularization to preserve structural properties within each view. The optimization is performed using two efficient proximal linearization-incorporated block coordinate descent algorithms. Extensive experiments on four gold-standard datasets and a larger real-world dataset demonstrate that our models consistently outperform state-of-the-art single-view, multi-view and deep learning-based DTI prediction methods. Furthermore, ablation studies confirm the contribution of each model component, and scalability analysis highlights the computational efficiency of our approach.