GHGPR-PPIS: A graph convolutional network for identifying protein-protein interaction site using heat kernel with Generalized PageRank techniques and edge self-attention feature processing block

Abstract

Accurately pinpointing protein-protein interaction site (PPIS) on the molecular level is of utmost significance for annotating protein function and comprehending the mechanisms underpinning various diseases. While numerous computational methods for predicting PPIS have emerged, they have indeed mitigated the labor and time constraints associated with traditional experimental methods. However, the predictive accuracy of these methods has yet to reach the desired threshold. In this context, we proposed a groundbreaking graph-based computational model called GHGPR-PPIS. This innovative model leveraged a graph convolutional network using heat kernel (GraphHeat) in conjunction with Generalized PageRank techniques (GHGPR) to predict PPIS. Additionally, building upon the GHGPR framework, we devised an edge self-attention feature processing block, further augmenting the performance of the model. Experimental findings conclusively demonstrated that GHGPR-PPIS surpassed all competing state-of-the-art models when evaluated on the benchmark test set. Impressively, on two distinct independent test sets and a specific protein chain, GHGPR-PPIS consistently demonstrated superior generalization performance and practical applicability compared to the comparative model, AGAT-PPIS. Lastly, leveraging the t-SNE dimensionality reduction algorithm and clustering visualization technique, we delved into an interpretability analysis of the effectiveness of GHGPR-PPIS by meticulously comparing the outputs from different stages of the model.