A Grid-based Simulation Model for the Evolution of Influenza A Viruses

We propose a simulation approach for analyzing and predicting the evolution of influenza A viruses (IAVs). The simulation is conducted in a sequence-based space to constrain the evolutionary trends within a grid of clusters of protein sequences. The simulated trajectories enable the investigation into point mutations on a protein strain of IAVs in evolution, which cannot be accomplished easily by analyses of phylogenetic trees. We tested the simulation model on three IAV internal proteins, NP, PB1 and PB2. The produced evolutionary pathways were consistent with previous studies of the reassortment history of the 2009 human pandemic. In addition, the chronological analysis of host-associated signature mutations on NP, PB1 and PB2 also agreed with the previous findings.