The Study of Hepatitis B Virus Using Bioinformatics

Bell, Trevor Graham; Kramvis, Anna

doi:10.5772/63076

Cited by 4 publications

(2 citation statements)

References 81 publications

(83 reference statements)

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“…A number of commercially available assays are available, for example, genotype‐specific probes assay (Smitest HBV Genotyping Kit, Genome Science, Fukushima, Japan), reverse hybridization of PCR products to probes on nitrocellulose strips (the line probe assay, LiPa™, Innogenetic Inc, Gent, Belgium) and enzyme linked immunosorbent assay (ELISA) (HBV Genotype EIA, Institute of Immunology, Tokyo, Japan). Each one has its advantages and disadvantages , which should be taken into account, when selecting the genotyping method appropriate for a particular study or application .…”

Section: Genotyping and Subgenotyping Methodsmentioning

confidence: 99%

The clinical implications of hepatitis B virus genotypes and HBeAg in pediatrics

Kramvis

2016

Rev. Med. Virol.

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SummaryAlthough a successful vaccine against HBV has been implemented in 184 countries, eradication of hepatitis B virus (HBV) is still not on the horizon. There are over 240 million chronic carriers of HBV globally. The risk of developing chronic hepatitis ranges from >90% in newborns of hepatitis Be antigen (HBeAg)‐positive mothers, 25%–35% in children under 5 years of age and <5% in adults. HBeAg, a non‐particulate viral protein, is a marker of HBV replication. This is the only HBV antigen to cross the placenta, leading to specific unresponsiveness of helper T cells to the capsid protein and HBeAg in newborns. HBeAg is tolerated in utero and acts as a tolerogen after birth. Perinatal transmission is frequent when mothers are HBeAg‐positive, whereas it occurs less frequently when mothers are HBeAg‐negative. Sequence heterogeneity is a feature of HBV. Based on an intergroup divergence >7.5% across the complete genome, HBV is classified phylogenetically into at least nine genotypes. With between ~4% and 8% intergroup nucleotide divergence, genotypes A–D, F, H and I are classified further into subgenotypes. HBV genotypes/subgenotypes may have distinct geographical distribution and can develop different mutations in the regions of the HBV genome that code for HBeAg. These differences can be related to the role of HBV genotypes to the natural history of infection and mode of transmission. Thus genotypes/subgenotypes of HBV can be responsible for the different natural history of infection and modes of transmission in children, found in various regions of the world, where different genotypes/subgenotypes prevail. Copyright © 2016 John Wiley & Sons, Ltd.

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Section: Genotyping and Subgenotyping Methodsmentioning

confidence: 99%

The clinical implications of hepatitis B virus genotypes and HBeAg in pediatrics

Kramvis

2016

Rev. Med. Virol.

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“…The evolution rate of HBV ranges from 1.8 × 10 − 2 to 1.5 × 10 − 5 nucleotide substitutions/site/year [ 61 – 63 ], while that of the human genome is 1.1–3 × 10 − 8 nucleotide substitutions/site/generation [ 64 ]. Furthermore, HBV has differences in genomic lengths among 10 HBV genotypes (from 3182 to 3248 base pairs), which could result in genotype alignments containing several regions of gaps [ 65 ].…”

Section: Introductionmentioning

confidence: 99%

Applications of next-generation sequencing analysis for the detection of hepatocellular carcinoma-associated hepatitis B virus mutations

Liu

Chang

2018

J Biomed Sci

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BackgroundNext-generation sequencing (NGS) is a powerful and high-throughput method for the detection of viral mutations. This article provides a brief overview about optimization of NGS analysis for hepatocellular carcinoma (HCC)-associated hepatitis B virus (HBV) mutations, and hepatocarcinogenesis of relevant mutations.Main bodyFor the application of NGS analysis in the genome of HBV, four noteworthy steps were discovered in testing. First, a sample-specific reference sequence was the most effective mapping reference for NGS. Second, elongating the end of reference sequence improved mapping performance at the end of the genome. Third, resetting the origin of mapping reference sequence could probed deletion mutations and variants at a certain location with common mutations. Fourth, using a platform-specific cut-off value to distinguish authentic minority variants from technical artifacts was found to be highly effective. One hundred and sixty-seven HBV single nucleotide variants (SNVs) were found to be studied previously through a systematic literature review, and 12 SNVs were determined to be associated with HCC by meta-analysis. From comprehensive research using a HBV genome-wide NGS analysis, 60 NGS-defined HCC-associated SNVs with their pathogenic frequencies were identified, with 19 reported previously. All the 12 HCC-associated SNVs proved by meta-analysis were confirmed by NGS analysis, except for C1766T and T1768A which were mainly expressed in genotypes A and D, but including the subgroup analysis of A1762T. In the 41 novel NGS-defined HCC-associated SNVs, 31.7% (13/41) had cut-off values of SNV frequency lower than 20%. This showed that NGS could be used to detect HCC-associated SNVs with low SNV frequency. Most SNV II (the minor strains in the majority of non-HCC patients) had either low (< 20%) or high (> 80%) SNV frequencies in HCC patients, a characteristic U-shaped distribution pattern. The cut-off values of SNV frequency for HCC-associated SNVs represent their pathogenic frequencies. The pathogenic frequencies of HCC-associated SNV II also showed a U-shaped distribution. Hepatocarcinogenesis induced by HBV mutated proteins through cellular pathways was reviewed.ConclusionNGS analysis is useful to discover novel HCC-associated HBV SNVs, especially those with low SNV frequency. The hepatocarcinogenetic mechanisms of novel HCC-associated HBV SNVs defined by NGS analysis deserve further investigation.

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Bioinformatic curation and alignment of genotyped hepatitis B virus (HBV) sequence data from the GenBank public database

2016

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Background Hepatitis B virus (HBV) DNA sequence data from thousands of samples are present in the public sequence databases. No publicly available, up-to-date, multiple sequence alignments, containing full-length and subgenomic fragments per genotype, are available. Such alignments are useful in many analysis applications, including data-mining and phylogenetic analyses.ResultsBy issuing a query, all HBV sequence data from the GenBank public database was downloaded (67,893 sequences). Full-length and subgenomic sequences, which were genotyped by the submitters (30,852 sequences), were placed into a multiple sequence alignment, for each genotype (genotype A: 5868 sequences, B: 4630, C: 7820, D: 8300, E: 2043, F: 985, G: 189, H: 108, I: 23), according to the results of offline BLAST searches against a custom reference library of full-length sequences. Further curation was performed to improve the alignment.Conclusions The algorithm described in this paper generates, for each of the nine HBV genotypes, multiple sequence alignments, which contain full-length and subgenomic fragments. The alignments can be updated as new sequences become available in the online public sequence databases. The alignments are available at http://hvdr.bioinf.wits.ac.za/alignments.

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The Study of Hepatitis B Virus Using Bioinformatics

Cited by 4 publications

References 81 publications

The clinical implications of hepatitis B virus genotypes and HBeAg in pediatrics

The clinical implications of hepatitis B virus genotypes and HBeAg in pediatrics

Applications of next-generation sequencing analysis for the detection of hepatocellular carcinoma-associated hepatitis B virus mutations

Bioinformatic curation and alignment of genotyped hepatitis B virus (HBV) sequence data from the GenBank public database

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