HepSEQ: International Public Health Repository for Hepatitis B

Gnaneshan, Saravanamuttu; Ijaz, Samreen; Moran, Joanne; Ramsay, Mary; Green, Jonathan

doi:10.1093/nar/gkl874

Cited by 18 publications

(15 citation statements)

References 21 publications

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“…Thus, HBV and several other viruses can currently be genotyped using the NCBI web-based HBV genotyping tool [25] . To further facilitate HBV genotype determination, several experts in the field have introduced different online HBV genotyping tools, such as the hepatitis B virus database (HBVdb) [26] , HBV STAR [27] , BioAfrica-Oxford HBV Automated Subtyping Tool [28] , HepSEQ Genotyper [29,30] and the jumping profile Hidden Markov Model (jpHMM) [31] .…”

Section: Online Methods To Genotype Hbvmentioning

confidence: 99%

Molecular identification of hepatitis B virus genotypes/subgenotypes: Revised classification hurdles and updated resolutions

Pourkarim¹

2014

WJG

163

177

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The clinical course of infections with the hepatitis B virus (HBV) substantially varies between individuals, as a consequence of a complex interplay between viral, host, environmental and other factors. Due to the high genetic variability of HBV, the virus can be categorized into different HBV genotypes and subgenotypes, which considerably differ with respect to geographical distribution, transmission routes, disease progression, responses to antiviral therapy or vaccination, and clinical outcome measures such as cirrhosis or hepatocellular carcinoma. However, HBV (sub)genotyping has caused some controversies in the past due to misclassifications and incorrect interpretations of different genotyping methods. Thus, an accurate, holistic and dynamic classification system is essential. In this review article, we aimed at highlighting potential pitfalls in genetic and phylogenetic analyses of HBV and suggest novel terms for HBV classification. Analyzing full-length genome sequences when classifying genotypes and subgenotypes is the foremost prerequisite of this classification system. Careful attention must be paid to all aspects of phylogenetic analysis, such as bootstrapping values and meeting the necessary thresholds for (sub)genotyping. Quasi-subgenotype refers to subgenotypes that were incorrectly suggested to be novel. As many of these strains were misclassified due to genetic differences resulting from recombination, we propose the term "recombino-subgenotype". Moreover, immigration is an important confounding facet of global HBV distribution and substantially changes the geographic pattern of HBV (sub)genotypes. We therefore suggest the term "immigro-subgenotype" to distinguish exotic (sub)genotypes from native ones. We are strongly convinced that applying these two proposed terms in HBV classification will help harmonize this rapidly progressing field and allow for improved prophylaxis, diagnosis and treatment.

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Section: Online Methods To Genotype Hbvmentioning

confidence: 99%

Molecular identification of hepatitis B virus genotypes/subgenotypes: Revised classification hurdles and updated resolutions

Pourkarim¹

2014

WJG

163

177

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“…The accuracy of our genotyping tool is similar to Oxford (20,30), jpHMM (21) and NCBI (22) HBV genotyping tools, including recombinant genomes detection. The HepSEQ genotyping tool (17) uses only polymerase/surface genes in genotype computation and is less accurate in recombinant detection (Supplementary Tables S1 and S2). …”

Section: Genotypingmentioning

confidence: 99%

“…To allow researchers to investigate the genetic variability of HBV sequences and viral resistance to treatment, several databases and repositories (17–19) have been published to date. Moreover, tools specific to HBV genotyping (20–22) are available for virologists, as well as tools aimed at drug resistance mutations analysis, among which some are freely accessible (23) and others need a registration (24).…”

Section: Introductionmentioning

confidence: 99%

HBVdb: a knowledge database for Hepatitis B Virus

Hayer¹,

Jadeau²,

Deléage³

et al. 2012

Nucleic Acids Research

183

178

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We have developed a specialized database, HBVdb (http://hbvdb.ibcp.fr), allowing the researchers to investigate the genetic variability of Hepatitis B Virus (HBV) and viral resistance to treatment. HBV is a major health problem worldwide with more than 350 million individuals being chronically infected. HBV is an enveloped DNA virus that replicates by reverse transcription of an RNA intermediate. HBV genome is optimized, being circular and encoding four overlapping reading frames. Indeed, each nucleotide of the genome takes part in the coding of at least one protein. However, HBV shows some genome variability leading to at least eight different genotypes and recombinant forms. The main drugs used to treat infected patients are nucleos(t)ides analogs (reverse transcriptase inhibitors). Unfortunately, HBV mutants resistant to these drugs may be selected and be responsible for treatment failure. HBVdb contains a collection of computer-annotated sequences based on manually annotated reference genomes. The database can be accessed through a web interface that allows static and dynamic queries and offers integrated generic sequence analysis tools and specialized analysis tools (e.g. annotation, genotyping, drug resistance profiling).

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“…There are two HBV sequence databases that allow users to download genotype-specific alignments of different HBV genes (Gnaneshan et al, 2007; Shin et al, 2008). However, these databases do not contain information on the N(t)RTIs received by the individuals from whom the sequenced viruses were obtained.…”

Section: Introductionmentioning

confidence: 99%

Hepatitis B virus reverse transcriptase sequence variant database for sequence analysis and mutation discovery

et al. 2010

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Drug resistance resulting from reverse transcriptase (RT) mutations is one of the main obstacles to successful hepatitis B virus (HBV) therapy. Indeed, HBV treatment guidelines recommend HBV genotypic resistance testing for patients receiving nucleos(t)ide RT inhibitors (N(t)RTIs) who develop virological failure. N(t)RTI-resistance mutations at 10 RT positions have been well characterized in phenotypic studies, however, data are lacking on the relative frequency of these mutations in N(t)RTI-treated and untreated individuals. There are also few published data on the extent of amino acid variation at most of the 344 positions of HBV RT and the extent to which this variation is influenced by N(t)RTI treatment. We retrieved 23,871 HBV RT sequences from GenBank and reviewed the published reports of these sequences to ascertain the number of individuals from whom the sequences were obtained, the N(t)RTI treatments of these individuals, and the year and region of virus sampling. We then used these data to populate a relational database we named HBVrtDB. As of July 2010, HBVrtDB contained 6,811 sequences from 3,869 individuals reported in 281 references. Among these 3,869 individuals, 73% were N(t)RTI-naïve and 27% received one or more N(t)RTIs. Among the 10 well-characterized N(t)RTI-resistance mutations, L80I/V, V173L, L180M, A181T, T184S, S202G and M204I/V were significantly associated with treatment with lamivudine, an L-nucleoside analog, and A181S/T/V and N236T were significantly associated with treatment with adefovir, an acyclic nucleoside phosphonate. A similar analysis of ten additional less well-characterized resistance mutations demonstrated a significant association with N(t)RTI treatment for four of the mutations: L82M, S85A, A200V, and Q215S. We also created an interactive program, HBVseq, to enable users to identify mutations in submitted sequences and retrieve the prevalence of these mutations in HBVrtDB according to genotype and N(t)RTI treatment. HBVrtDB and HBVseq are available at http://hivdb.stanford.edu/HBV/releaseNotes/

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HepSEQ: International Public Health Repository for Hepatitis B

Cited by 18 publications

References 21 publications

Molecular identification of hepatitis B virus genotypes/subgenotypes: Revised classification hurdles and updated resolutions

Molecular identification of hepatitis B virus genotypes/subgenotypes: Revised classification hurdles and updated resolutions

HBVdb: a knowledge database for Hepatitis B Virus

Hepatitis B virus reverse transcriptase sequence variant database for sequence analysis and mutation discovery

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