An End-to-end Knowledge Graph Fused Graph Neural Network for Accurate Protein-Protein Interactions Prediction.

Abstract

Protein-protein interactions (PPIs) are essential to understanding cellular mechanisms, signaling networks, disease processes, and drug development, as they represent the physical contacts and functional associations between proteins. Recent advances have witnessed the achievements of artificial intelligence (AI) methods aimed at predicting PPIs. However, these approaches often handle the intricate web of relationships and mechanisms among proteins, drugs, diseases, ribonucleic acid (RNA), and protein structures in a fragmented or superficial manner. This is typically due to the limitations of non-end-to-end learning frameworks, which can lead to sub-optimal feature extraction and fusion, thereby compromising the prediction accuracy. To address these deficiencies, this paper introduces a novel end-to-end learning model, the Knowledge Graph Fused Graph Neural Network (KGF-GNN). This model comprises three integral components: (1) Protein Associated Network (PAN) Construction: We begin by constructing a PAN that extensively captures the diverse relationships and mechanisms linking proteins with drugs, diseases, RNA, and protein structures. (2) Graph Neural Network for Feature Extraction: A Graph Neural Network (GNN) is then employed to distill both topological and semantic features from the PAN, alongside another GNN designed to extract topological features directly from observed PPI networks. (3) Multi-layer Perceptron for Feature Fusion: Finally, a multi-layer perceptron integrates these varied features through end-to-end learning, ensuring that the feature extraction and fusion processes are both comprehensive and optimized for PPI prediction. Extensive experiments conducted on real-world PPI datasets validate the effectiveness of our proposed KGF-GNN approach, which not only achieves high accuracy in predicting PPIs but also significantly surpasses existing state-of-the-art models. This work not only enhances our ability to predict PPIs with a higher precision but also contributes to the broader application of AI in Bioinformatics, offering profound implications for biological research and therapeutic development.