Hepatitis Virus Projects
Hepatitis viruses are a diverse group of pathogens that primarily affect the liver, leading to inflammation and a range of clinical outcomes, including acute and chronic liver disease, cirrhosis, and hepatocellular carcinoma. The main types of hepatitis viruses include hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV). Each virus has distinct transmission routes, with HAV and HEV primarily spread through contaminated food and water, while HBV, HCV, and HDV are transmitted through blood and bodily fluids. The global burden of hepatitis virus infections is significant, with millions of people affected worldwide, particularly in regions with inadequate healthcare infrastructure, increasing the risk of severe liver complications and posing substantial public health challenges.
Control and prevention strategies for hepatitis viruses are critical in mitigating their impact on global health. Vaccination is effective for hepatitis A and B, significantly reducing the incidence of these infections in vaccinated populations. For hepatitis C, antiviral therapies have advanced significantly, with direct-acting antivirals achieving high cure rates in infected individuals. Despite these advancements, many hepatitis virus infections remain undiagnosed and untreated, particularly in low-resource settings. Continued research is essential to enhance understanding of hepatitis viruses, their epidemiology, and the development of new diagnostic tools and therapeutic options. By improving awareness and access to care, public health initiatives can address the growing challenge of hepatitis virus infections, ultimately reducing the burden of liver disease globally.
During the development of GLUE at the University of Glasgow Centre for Virus Research (CVR), particular emphasis was placed on hepatitis viruses, reflecting the CVR's focus on hepatitis research at that time. Several hepatitis-related projects were initiated as part of this effort, showcasing the flexibility of the GLUE framework in managing virus genomic data and supporting collaborative research. While web interfaces were created for some of these projects, the CVR continues to host and maintain online instances for certain hepatitis viruses to this day, providing ongoing access to these resources for the research community.
This page provides a comprehensive list of GLUE projects developed for viruses that cause hepatitis in humans:
Hepatitis B virus (HBV) is a member of the Hepadnaviridae family and is a major global health concern, causing both acute and chronic liver disease. With a circular, partially double-stranded DNA genome of approximately 3.2 kb, HBV replicates via reverse transcription, a unique feature among DNA viruses. It is highly infectious and transmitted through blood, sexual contact, and from mother to child during childbirth. Chronic HBV infection is a leading cause of liver cirrhosis and hepatocellular carcinoma (HCC), contributing to an estimated 820,000 deaths per year worldwide. The virus displays significant genetic diversity, classified into at least nine genotypes (A-I) and several subgenotypes, which exhibit distinct geographical distributions and are associated with different clinical outcomes and responses to treatment.
Efforts to control HBV have been aided by the availability of a highly effective prophylactic vaccine, which has significantly reduced the incidence of new infections in countries with high vaccine coverage. However, challenges remain, as chronic infections persist in approximately 296 million individuals globally, particularly in low- and middle-income countries. Antiviral therapies, including nucleos(t)ide analogs, can suppress viral replication but rarely achieve a complete cure, necessitating lifelong treatment for many patients. Research continues to focus on understanding HBV pathogenesis, immune evasion mechanisms, and the development of novel therapeutic strategies, including immune-modulatory treatments and functional cure approaches aimed at eliminating or controlling the virus in chronically infected individuals.
HBV-GLUE is a bioinformatics resource for HBV genome sequence data. A web version has been developed and an instance of this is hosted by the University of Glasgow CVR. The web version can be used for basic analysis, while the offline version can be installed by bioinformaticians and used for more advanced work.
HBV-GLUE addresses a key challenge to the development of HBV genomics resources: the circular genome. The circular nature of HBV's genome complicates genomic analysis due to varying definitions of the "start" position, leading to inconsistencies in nucleotide numbering across different studies. This lack of standardization makes sequence alignment, mutation mapping, and gene annotation more difficult, especially given the genome's overlapping genes and compact structure. Tools designed for circular genomes and standardized reference sequences help address these issues by providing a common framework for consistent nucleotide numbering and accurate comparisons across datasets. GLUE provides commands for rotating sequences that can address the complications arising from different "start" positions.
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HBV Sequence Database:
- Daily updated database of HBV sequences and metadata from NCBI, organized by clades (genotypes, subgenotypes).
- Annotated reference sequences for detailed comparative genomic analysis, including conservation, adaptation, structural context, and genotype-to-phenotype associations.
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Pre-built Alignments:
- Comprehensive multiple-sequence alignments of HBV sequences from NCBI, available for use, export, or download in customizable sections.
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Sequence Analysis Tools:
- Automated Genotyping: Performs automated genotyping of HBV sequences, including subgenomic regions, using GLUE's maximum likelihood clade assignment (MLCA) algorithm.
- Deep Sequencing Data Analysis: Supports the analysis of next-generation sequencing (NGS) data (SAM/BAM files), enabling high-resolution analysis of sequence variation and drug resistance.
- Phylogenetic Analysis: Tools for exploring evolutionary relationships of HBV sequences, supporting genotyping and comparative genomic studies.
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Exploratory Bioinformatics Tools:
- A rich set of bioinformatics functions for private data exploration, including tools for filtering, querying, and analyzing HBV sequence and metadata.
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Automated Data Updates:
- Continuously updated HBV sequence data, ensuring access to the latest information for genomic and evolutionary analysis.
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Web User Interface (Optional):
- A web-based interface for browsing the HBV sequence database, running sequence analysis tasks (e.g., genotyping, drug resistance analysis), and visualizing phylogenetic relationships and other results online in real-time.
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Operational Applications:
- Designed for both research and operational settings, providing standardized sequence analysis reports (e.g., genotyping, drug resistance analysis) and supporting HBV-related research and public health initiatives.
| Virus | Hepatitis B virus (HBV) |
|---|---|
| Development Period | 2016-2019 |
| Lead Developer | Josh Singer |
| Main Objectives | Genotyping, Drug Resistance Analysis |
| Data Sources | NCBI |
| Associated Tools | BLAST+, MAFFT, RAXML |
| Offline Project | GitHub |
| Online Access | University of Glasgow CVR |
| Status | Mature. Not currently being developed |
| User Guide | None yet |
- NCBI-HBV-GLUE: extends HBV-GLUE through the incorporation of all HBV sequence data published in NCBI GenBank.
- HBV-DRUG-RESISTANCE : a drug resistance-focused extension incorporating an analysis tool that provides genotypic assessment of drug resistance/susceptibility.
- HBV-GLUE-WEB: a web interface that can be used to create a HBV-GLUE web-server.
Hepatitis C virus (HCV) is a bloodborne RNA virus that primarily targets the liver, causing both acute and chronic hepatitis. Classified under the Hepacivirus genus within the Flaviviridae family, HCV is mainly transmitted through contact with infected blood. If left untreated, infection can lead to serious liver complications, such as cirrhosis and liver cancer. Direct-acting antiviral medications have dramatically improved cure rates and hold the potential to eliminate the virus. However, achieving global elimination faces significant challenges
HCV-GLUE was developed between 2015 and 2020 in response to an internal need for computational resources to support CVR HCV research. The project led to the implementation of a web-based HCV-GLUE resource that remains hosted by the CVR, although active development has now slowed. HCV-GLUE continues to offer an essential toolset for HCV researchers globally, though it has perhaps been underutilized, possibly due to limited promotion and dissemination.
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HCV Sequence Database:
- Daily updated database of HCV sequences and metadata from NCBI, organized by clades (genotypes, subtypes).
- Annotated reference sequences for detailed comparative genomic analysis of conservation, adaptation, structural context, and genotype-to-phenotype associations.
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Drug Resistance Database: Curated database of direct-acting antiviral (DAA)-resistant polymorphisms, developed with the Virus Reference Department (now the UK Health Security Agency).
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Sequence Analysis Tools:
- Automated Genotyping: Performs automated genotyping of HCV sequences, including subgenomic regions, using GLUE's maximum likelihood clade assignment (MLCA) algorithm.
- Resistance Analysis: Tools for genotyping and drug resistance analysis for submitted FASTA sequences.
- NGS Sequence Analysis: Supports the analysis of next-generation sequencing (NGS) data (SAM/BAM files), including drug resistance analysis.
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Automated Data Updates: Continuously updated HCV sequence data, ensuring access to the latest information for genomic analysis.
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Pre-built Alignments: Multiple-sequence alignments of NCBI sequences available for use/export/download in user-defined sections.
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Exploratory Bioinformatics Tools: Rich set of bioinformatics functions for data exploration, including phylogenetic analysis to examine evolutionary relationships.
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Web User Interface: A web interface for browsing the HCV sequence database, running sequence analysis (e.g., genotyping, drug resistance), and visualizing results online.
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Operational Applications: Useful in both research and operational settings for generating standardized sequence analysis reports (e.g., drug resistance analysis) and supporting HCV research.
| Virus | Hepatitis C virus (HCV) |
|---|---|
| Development Period | 2016-2020 |
| Lead Developer | Josh Singer |
| Main Objectives | Genotyping, Drug Resistance Analysis, Vaccine Development |
| Data Sources | NCBI |
| Associated Tools | BLAST+, MAFFT, RAXML |
| Offline Project | GitHub |
| Online Access | University of Glasgow CVR |
| Status | Mature. Not currently being developed |
| User Guide | GitHub Link |
HCV-GLUE can be extended with additional layers, openly available via GitHub, including:
- NCBI-HCV-GLUE: extends HCV-GLUE through the incorporation of all HCV sequence data published in NCBI GenBank.
- PHE-HCV-DRUG-RESISTANCE: a drug resistance-focused extension incorporating an analysis tool that provides genotypic assessment of drug resistance/susceptibility.
- HCV-NABS: an extension for analysing neutralising antibody binding sites in HCV.
Hepatitis E virus (HEV)is an important cause of viral hepatitis, primarily transmitted through the fecal-oral route, especially in regions with inadequate sanitation. It is a member of the Hepeviridae family and has four main genotypes, with genotypes 1 and 2 typically associated with outbreaks in developing countries, while genotypes 3 and 4 are linked to zoonotic transmission in developed countries. Symptoms of HEV infection include fatigue, jaundice, abdominal pain, and loss of appetite, with most cases resolving spontaneously. However, the virus can lead to severe complications, particularly in pregnant women, and chronic infection may occur in immunocompromised individuals. Continued research is vital to understand HEV's epidemiology and improve prevention and treatment strategies.
HEV-GLUE was developed at the University of Glasgow Centre for Virus Research (CVR) from 2015-2016. HEV was the first virus to which the GLUE software framework was applied. It provided a test of GLUE's capabilities, following the release of an early version of the framework. The project led to the implementation of a web-based HEV-GLUE resource, which was hosted by the CVR, but has now been discontinued.
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HEV Sequence Database:
- A curated database of HEV sequences from NCBI Nucleotide (GenBank), enriched with comprehensive metadata.
- Categorization of sequences into clades (genotypes, subtypes) for organized comparative genomic analysis.
- Annotated reference sequences that support in-depth investigations of HEV genomic variation and evolution.
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Pre-built Alignments:
- Curated multiple-sequence alignments of HEV sequences from NCBI, organized by clade, available for export and download in user-defined sections.
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Sequence Analysis Tools:
- Automated Genotyping: Provides automated genotyping of HEV sequences, assigning genotypes and subgenotypes using GLUE's maximum likelihood clade assignment (MLCA) algorithm.
- Comparative Genomics: Supports interpretation of submitted consensus FASTA sequences, allowing users to explore HEV's genetic diversity and evolutionary relationships.
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Exploratory Bioinformatics Tools:
- A set of tools for private data exploration, enabling filtering, querying, and visualization of metadata and sequence data for detailed genomic research.
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Automated Data Updates:
- Regular updates to HEV sequence data from NCBI, ensuring continuous access to the latest information for genomic analysis.
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Web User Interface (Historical):
- The project initially featured a web interface that allowed browsing of the HEV sequence database and running sequence analysis tasks, but this online resource has since been discontinued.
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Operational Applications:
- Useful in both research and public health contexts for generating standardized sequence analysis reports and supporting studies into HEV transmission, zoonotic links, and epidemiology.
| Virus | Hepatitis E virus (HEV) |
|---|---|
| Development Period | 2016-2019 |
| Lead Developer | Josh Singer |
| Main Objectives | Genotyping |
| Data Sources | NCBI |
| Associated Tools | BLAST+, MAFFT, RAXML |
| Offline Project | GitHub Link |
| Online Access | University of Glasgow CVR, (Discontinued) |
| Status | Mature. Not currently being developed |
| User Guide | None yet |
GLUE by Robert J. Gifford Lab.
For questions, issues, or feedback, please open an issue on the GitHub repository.