A robust protein language model for SARS-CoV-2 protein–protein interaction network prediction

Protein-protein interaction is one of the ways viruses interact with their hosts. Therefore, identifying protein interactions between viruses and hosts helps explain how virus proteins work, how they replicate, and how they cause disease. SARS-CoV-2 is a new type of virus that emerged from the coronavirus family in 2019 and caused a worldwide pandemic. Detection of human proteins interacting with this novel virus strain plays an important role in monitoring the cellular process of virus-associated infection. Within the scope of the study, a natural language processing-based collective learning method is proposed for the prediction of potential SARS-CoV-2-human PPIs. Protein language models were obtained with the prediction-based word2Vec and doc2Vec embedding methods and the frequency-based tf-idf method. Known interactions were represented by proposed language models and traditional feature extraction methods (conjoint triad and repeat pattern), and their performances were compared. The interaction data were trained with support vector machine, artificial neural network (ANN), k-nearest neighbor (KNN), naive Bayes (NB), decision tree (DT), and ensemble algorithms. Experimental results show that protein language models are a promising protein representation method for protein-protein interaction prediction. The term frequency-inverse document frequency-based language model performed the SARS-CoV-2 protein-protein interaction estimation with an error of 1.4%. Additionally, the decisions of high-performing learning models for different feature extraction methods were combined with a collective voting approach to make new interaction predictions. For 10,000 human proteins, 285 new potential interactions were predicted, with models combining decisions.