Integration of protein sequence and protein–protein interaction data by hypergraph learning to identify novel protein complexes

Abstract

Abstract Protein–protein interactions (PPIs) are the basis of many important biological processes, with protein complexes being the key forms implementing these interactions. Understanding protein complexes and their functions is critical for elucidating mechanisms of life processes, disease diagnosis and treatment and drug development. However, experimental methods for identifying protein complexes have many limitations. Therefore, it is necessary to use computational methods to predict protein complexes. Protein sequences can indicate the structure and biological functions of proteins, while also determining their binding abilities with other proteins, influencing the formation of protein complexes. Integrating these characteristics to predict protein complexes is very promising, but currently there is no effective framework that can utilize both protein sequence and PPI network topology for complex prediction. To address this challenge, we have developed HyperGraphComplex, a method based on hypergraph variational autoencoder that can capture expressive features from protein sequences without feature engineering, while also considering topological properties in PPI networks, to predict protein complexes. Experiment results demonstrated that HyperGraphComplex achieves satisfactory predictive performance when compared with state-of-art methods. Further bioinformatics analysis shows that the predicted protein complexes have similar attributes to known ones. Moreover, case studies corroborated the remarkable predictive capability of our model in identifying protein complexes, including 3 that were not only experimentally validated by recent studies but also exhibited high-confidence structural predictions from AlphaFold-Multimer. We believe that the HyperGraphComplex algorithm and our provided proteome-wide high-confidence protein complex prediction dataset will help elucidate how proteins regulate cellular processes in the form of complexes, and facilitate disease diagnosis and treatment and drug development. Source codes are available at https://github.com/LiDlab/HyperGraphComplex.