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Araujo","year":"2012","journal-title":"J Gen Virol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1159\/000227078","article-title":"Mutations on free and integrated hepatitis B virus DNA in a hepatocellular carcinoma: footprints of homologous recombination","volume":"49","author":"P Georgi-Geisberger","year":"1992","journal-title":"Oncology"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.virol.2012.01.030","article-title":"Identification of novel inter-genotypic recombinants of human hepatitis B viruses by large-scale phylogenetic analysis","volume":"427","author":"W Shi","year":"2012","journal-title":"Virology"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1099\/vir.0.81752-0","article-title":"Identification of Hepatitis B virus putative intergenotype recombinants by using fragment typing","volume":"87","author":"J Yang","year":"2006","journal-title":"J Gen 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J Hepatol","volume":"50","year":"2009","journal-title":"European Association for the Study of the Liver"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.antiviral.2013.03.007","article-title":"A comparative study of ultra-deep pyrosequencing and cloning to quantitatively analyze the viral quasispecies using hepatitis B virus infection as a model","volume":"98","author":"C Ram\u00edrez","year":"2013","journal-title":"Antiviral Res"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"e83361","DOI":"10.1371\/journal.pone.0083361","article-title":"Ultra-Deep Pyrosequencing (UDPS) Data Treatment to Study Amplicon HCV Minor Variants","volume":"8","author":"J Gregori","year":"2013","journal-title":"PLoS One"},{"key":"ref28","unstructured":"R: The R Project for Statistical Computing [Internet]. [Accessed 14 Apr 2015]. Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.r-project.org\/\" xlink:type=\"simple\">http:\/\/www.r-project.org\/<\/ext-link>"},{"key":"ref29","unstructured":"Pages H, Aboyoun P, Gentleman R, DebRoy S. Bioconductor\u2014Biostrings [Internet]. [Accessed 14 Apr 2015]. Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.bioconductor.org\/packages\/release\/bioc\/html\/Biostrings.html\" xlink:type=\"simple\">http:\/\/www.bioconductor.org\/packages\/release\/bioc\/html\/Biostrings.html<\/ext-link>"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1093\/bioinformatics\/btg412","article-title":"APE: Analyses of Phylogenetics and Evolution in R language","volume":"20","author":"E Paradis","year":"2004","journal-title":"Bioinformatics"},{"key":"ref31","first-page":"459","article-title":"Statistical AData analysis and Interference","author":"C Cuadras","year":"1989"},{"key":"ref32","unstructured":"Cuadras C. A distance approach to discriminant analysis and its properties. Mathematics preprint series. Barcelona; 1991."},{"key":"ref33","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/BF01731581","article-title":"A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences","volume":"16","author":"M Kimura","year":"1980","journal-title":"J Mol Evol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1007\/s002390010118","article-title":"Efficiency of the neighbor-joining method in reconstructing deep and shallow evolutionary relationships in large phylogenies","volume":"51","author":"S Kumar","year":"2000","journal-title":"J Mol Evol"},{"key":"ref35","author":"I Borg","year":"2005"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jcv.2007.05.009","article-title":"Central African Republic is part of the West-African hepatitis B virus genotype E crescent","volume":"40","author":"C Bekondi","year":"2007","journal-title":"J Clin Virol"},{"key":"ref37","first-page":"86","article-title":"Genotypes, mutations, and viral load of hepatitis B virus and the risk of hepatocellular carcinoma: HBV properties and hepatocarcinogenesis","volume":"11","author":"Q Zhang","year":"2011","journal-title":"Hepat Mon"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"15467","DOI":"10.1128\/JVI.79.24.15467-15476.2005","article-title":"Recombination in the genesis and evolution of hepatitis B virus genotypes","volume":"79","author":"P Simmonds","year":"2005","journal-title":"J Virol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"2729","DOI":"10.1099\/vir.0.053041-0","article-title":"Role of the line probe assay INNO-LiPA HBV DR and ultradeep pyrosequencing in detecting resistance mutations to nucleoside\/nucleotide analogues in viral samples isolated from chronic hepatitis B patients","volume":"94","author":"S Mese","year":"2013","journal-title":"J Gen Virol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1002\/hep.20831","article-title":"Hepatitis B viral kinetics: A dynamic puzzle still to be resolved","volume":"42","author":"AU Neumann","year":"2005","journal-title":"Hepatology"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0144816","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T10:38:52Z","timestamp":1540291132000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0144816"}},"subtitle":[],"editor":[{"given":"Golo","family":"Ahlenstiel","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2015,12,29]]},"references-count":40,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2015,12,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0144816","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,29]]}}}