Abstract
Protein-protein interactions (PPIs) are extremely important for gaining mechanistic insights into the functional organization of the proteome. The resolution of PPI functions can help in the identification of novel diagnostic and therapeutic targets with medical utility, thus facilitating the development of new medications. However, the traditional methods for resolving PPI functions are mainly experimental methods, such as co-immunoprecipitation, pull-down assays, cross-linking, label transfer, and far-Western blot analysis, that are not only expensive but also time-consuming. In this study, we constructed an integrated feature selection scheme for the large-scale selection of the relevant functions of PPIs by using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotations of PPI participants. First, we encoded the proteins in each PPI with their gene ontologies and KEGG pathways. Then, the encoded protein features were refined as features of both positive and negative PPIs. Subsequently, Boruta was used for the initial filtering of features to obtain 5684 features. Three feature ranking algorithms, namely, least absolute shrinkage and selection operator, light gradient boosting machine, and max-relevance and min-redundancy, were applied to evaluate feature importance. Finally, the top-ranked features derived from multiple datasets were comprehensively evaluated, and the intersection of results mined by three feature ranking algorithms was taken to identify the features with high correlation with PPIs. Some functional terms were identified in our study, including cytokine-cytokine receptor interaction (hsa04060), intrinsic component of membrane (GO:0031224), and protein-binding biological process (GO:0005515). Our newly proposed integrated computational approach offers a novel perspective of the large-scale mining of biological functions linked to PPI.