Bioinformatics Methods Of Hepatitis B Virus Genotyping And Reorganization Of Detection,

One of basic mechanisms of evolution is the recombination which plays an important role in the process of evolution. The study of recombination also makes it possible for the researchers to have further understanding in the complexity of the evolution.Considering the importance of the recombination in the evolutional biology, the bioinformatics tools to detect recombination such as RDP3 package and Simplot program have been developed for the researchers to understand phylogenetics analysis.I studied the Hepatitis B virus in the past two years including its genotype and recombination. HBV is the pathogen of a widely distribution and more than 350 million people in the world were infected. It has high prevalence in South and East Asia including China.The data set of 829 HBV complete genome sequence was obtained from Hepatitis Virus Database. In Chapter 2, I classified HBV genotype according their genetic heterogeneity by using bioinformatics tools. First, the genotype information was gotten from text mining both NCBI entries and reference. Others are through BLASTn on the basis on the sequence similarity between different genotypes. Finally, the phylogenetic relationship using 791 human HBV full genome sequences was reconstructed to verify the genotype classification. There are 791 human HBV genomes plus 38 non-human primate HBV genomes were categorized into 8 genotypes A-H.In chapter 3, I tried to detect potential recombination events of 829 HBV genome sequences by five recombination methods in RDP3 Package: RDP, GENECONV, MaxChi, Chimaera and Siscan. To get more reliable results, the results of different five methods were combined by using a Perl script and 61 recombinants which were from 9 recombination events were obtained. six of nine events that have both two parental sequences were available for the Simplot program to determine the breakpoints precisely. We presented 61 putative intergenotype recombination found in 829 complete genome sequences supported by five recombination methods. And 53 of 61 recombinants were found for the first time to our knowledge. We also found the recombination between the human HBV and chimpanzee HBV. Our work also suggests that the PreC/C gene region and the position near gene boundaries show high frequency to recombine. Our findings provide new data on the study of the role of the recombination in the HBV evolution and differentiation of current HBV genotypes.In chapter 4,I discussed the further work: the adaptive selection of HBV genes, immune escape of HBV antigenic protein and evolution of HBV genotypes.