The rapid mutation of influenza viruses especially on the two surface proteins hemagglutinin (HA) and neuraminidase (NA) has made them capable to escape from population immunity, which has become a key challenge for influenza vaccine design. Thus, it is crucial to predict influenza antigenic evolution and identify new antigenic variants in a timely manner. However, traditional experimental methods like hemagglutination inhibition (HI) assay to select vaccine strains are time and labor-intensive, while popular computational methods are less sensitive, which presents the need for more accurate algorithms. In this study, we have proposed a novel low-rank matrix completion model MCAAS to infer antigenic distances between antigens and antisera based on partially revealed antigenic distances, virus similarity based on HA protein sequences, and vaccine similarity based on vaccine strains. The model exploits the correlations of viruses and vaccines in serological tests as well as the ability of HAs from viruses and vaccine strains in inferring influenza antigenicity. We also compared the effects of comprehensive 65 amino acids substitution matrices in predicting influenza antigenicity. As a result, we applied MCAAS into H3N2 seasonal influenza virus data. Our model achieved a 10-fold cross validation root-mean-squared error (RMSE) of 0.5982, significantly outperformed existing computational methods like antigenic cartography, AntigenMap and BMCSI. We also constructed the antigenic map and studied the association between genetic and antigenic evolution of H3N2 influenza viruses. Finally, our analyses showed that homologous structure derived amino acid substitution matrix (HSDM) is most powerful in predicting influenza antigenicity, which is consistent with previous studies.
Keywords: HA protein sequence information; antigenic map; hemagglutination inhibition assay; influenza antigenicity; low-rank matrix completion.