More than ten million deaths make influenza virus one of the deadliest of history. About half a million sever illnesses are annually reported consequent of influenza. Influenza is a parasite which needs the host cellular machinery to replicate its genome. To reach the host, viral proteins need to interact with the host proteins. Therefore, identification of host-virus protein interaction network (HVIN) is one of the crucial steps in treating viral diseases. Being expensive, time-consuming and laborious of HVIN experimental identification, force the researches to use computational methods instead of experimental ones to obtain a better understanding of HVIN. In this study, several features are extracted from physicochemical properties of amino acids, combined with different centralities of human protein-protein interaction network (HPPIN) to predict protein-protein interactions between human proteins and Alphainfluenzavirus proteins (HI-PPIs). Ensemble learning methods were used to predict such PPIs. Our model reached 0.93 accuracy, 0.91 sensitivity and 0.95 specificity. Moreover, a database including 694522 new PPIs was constructed by prediction results of the model. Further analysis showed that HPPIN centralities, gene ontology semantic similarity and conjoint triad of virus proteins are the most important features to predict HI-PPIs.

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