Advances in protein-protein interaction prediction: a deep learning perspective Alkhateeb and Awad 10.3389/fbinf.2025.1710937

Abstract

Protein-protein interactions (PPIs) are vital for regulating various cellular functions and understanding how diseases are developed. The traditional ways to identify the PPIs are costly and time-consuming. In recent years, the disruptive advances in deep learning (DL) have transformed computational PPI prediction by enabling automatic feature extraction from protein sequences and structures. This survey presents a comprehensive analysis of DL-based models developed for PPI prediction, including convolutional neural networks (CNNs), recurrent neural networks (RNNs), deep neural networks (DNNs), graph convolutional networks (GCNs), and ensemble architectures. The review compares their feature representations, learning strategies, and evaluation benchmarks, emphasizing their strengths and limitations in capturing complex dependencies and structural relationships. In addition, the paper elaborates on different benchmarks and biological databases that are commonly used in different experiments for performance comparison. Finally, we outline open challenges and future research directions to enhance model generalization, interpretability, and integration with biological knowledge for reliable PPI prediction.