Since 1999 we have developed two computational mutation approaches to ana-lyze the protein primary structure whose methodology and implications were re-viewed in 2002.Our first approach is the calculation of predictable and unpredict-able portions of amino-acid pairs in a protein,and the second is the calculation ofamino-acid distribution rank in a protein.Both approaches provide quantitativemeasures to present a protein,which we have used to study a number of proteinswith numerous mutations such as p53 proteins.More recently,we focussed ourefforts on analyzing the proteins mutating frequently over time such as hemagglu-tinins of influenza A viruses.In this review we summarise our findings and theirimplications for hemagglutinin mutations in combination with some newly avail-able data.Our approaches throw light on the true nature of genetic heterogeneityof influenza virus hemagglutinins;that is,the protein variability is highly relevantto its amino-acid construction.Using these approaches,we can monitor newmutations from influenza virus hemagglutinins and may predict their mutations inthe future. Since 1999 we have developed two computational mutation approaches to ana-lyze the protein primary structure who methodology and implications were re-viewed in 2002. Our first approach is the calculation of predictable and unpredict- able portions of amino-acid pairs in a protein, and the second is the calculation of amino-acid distribution rank in a protein. which we have used to study a number of proteins with more mutations such as p53 proteins. More recently, we focussed ourefforts on analyzing the proteins mutating frequently over time such as hemagglu-tinins of influenza A viruses. this review we summarise our findings and theimages for hemagglutinin mutations in combination with some newly avail-able data. Our approaches throw light on the true nature of genetic heterogeneity of influenza virus that is, the protein variability is highly relevant to its amino-acid construction. Use these approac hes, we can monitor new mutations from influenza virus hemagglutinins and may predict their mutations inthe future.