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Recently, the H5N1 virus has had an increasingly important impact on human life. This is because more and more people are becoming infected with this virus, and the possibility of a serious pandemic with human to human transmission is looming. This might occur if the genome of this influenza virus mutates either by antigenic drift or by antigenic shift, especially if there is a mutation of the hemagglutinin (HA) glycoprotein. The HA is the surface glycoprotein, and it binds to sialic acid of the host cell surface receptor. Thus, the combination of HA and sialic acid are central to whether influenza virus infects humans. In this study, we selected 497 HA protein sequences from the National Center for Biotechnology Information (NCBI) Influenza Resource database, and used a decision tree method to identify discriminative amino acids in the HA protein sequences that may possibly influence the binding of HA to sialic acid. Four such amino acid positions at 54, 55, 241, and 281 were identified and these may play an important role in infection by H5N1 influenza virus.