Key protein identification by integrating protein complex information and multi-biological features

Identifying key proteins based on protein-protein interaction networks has emerged as a prominent area of research in bioinformatics. However, current methods exhibit certain limitations, such as the omission of subcellular localization information and the disregard for the impact of topological structure noise on the reliability of key protein identification. Moreover, the influence of proteins outside a complex but interacting with proteins inside the complex on complex participation tends to be overlooked. Addressing these shortcomings, this paper presents a novel method for key protein identification that integrates protein complex information with multiple biological features. This approach offers a comprehensive evaluation of protein importance by considering subcellular localization centrality, topological centrality weighted by gene ontology (GO) similarity and complex participation centrality. Experimental results, including traditional statistical metrics, jackknife methodology metric and key protein overlap or difference, demonstrate that the proposed method not only achieves higher accuracy in identifying key proteins compared to nine classical methods but also exhibits robustness across diverse protein-protein interaction networks.