ABSTRACT
Since the emerge of the highly pathogenic avian H5N1 virus in Asia in 1996, the possibility for this virus to cross species barriers to infect humans and its ability to cause large outbreaks in birds have been a public health concern. This virus has been spreading from Asia to Europe and Africa by migratory birds with North America as its next possible stop. In this study, an ensemble of computational techniques including Random Forests, Informational Spectrum Method, Entropy, and Mutual Information were employed to unravel the distinct characteristics of Asian and North American avian H5N1 in comparison with human and swine H5N1. Critical differences were identified in the HA cleavage and binding sites, the HA receptor selection, the interaction patterns of HA and NA, and NP, PA, PB1, and PB2, and the important sites in the influenza proteins including HA, NA, M1, M2, NS1, NS2, NP, PA, PB1, PB1-F2, and PB2.