Inference of Genotype–Phenotype Relationships in the Antigenic Evolution of Human Influenza A (H3N2) Viruses

Lars Steinbrück, Alice Carolyn McHardy, Neil Ferguson
2012 PLoS Computational Biology  
Distinguishing mutations that determine an organism's phenotype from (near-) neutral 'hitchhikers' is a fundamental challenge in genome research, and is relevant for numerous medical and biotechnological applications. For human influenza viruses, recognizing changes in the antigenic phenotype and a strains' capability to evade pre-existing host immunity is important for the production of efficient vaccines. We have developed a method for inferring 'antigenic trees' for the major viral surface
more » ... otein hemagglutinin. In the antigenic tree, antigenic weights are assigned to all tree branches, which allows us to resolve the antigenic impact of the associated amino acid changes. Our technique predicted antigenic distances with comparable accuracy to antigenic cartography. Additionally, it identified both known and novel sites, and amino acid changes with antigenic impact in the evolution of influenza A (H3N2) viruses from 1968 to 2003. The technique can also be applied for inference of 'phenotype trees' and genotype-phenotype relationships from other types of pairwise phenotype distances.
doi:10.1371/journal.pcbi.1002492 pmid:22532796 pmcid:PMC3330098 fatcat:3cn4p26z75g27dnj2gqhxd6yqq