Virus Diversity Projects
The Gifford Lab has developed several GLUE projects that are designed to facilitate comparative genomic analysis across entire taxonomic groups, extending beyond a single virus to encompass entire genera or families.
These projects aim to support data sharing and re-use in comparative studies that address broader questions of viral ecology, evolution, and diversity. By integrating genomic data at this higher taxonomic level, researchers can explore evolutionary relationships and patterns of host-virus interactions that might not be apparent when focusing on individual viruses.
A key feature of these broader-scope projects is their incorporation of extension layers for endogenous viral elements (EVEs). This allows researchers to include ancient viral sequences in their analyses, providing deeper evolutionary context.
While these projects cover a wider range of viral diversity, they are also structured to serve as foundational resources. Researchers can build on these projects by developing extension layers that focus on more specific groups of viruses or even individual species, ensuring flexibility for a variety of research aims.
The following Gifford Lab GLUE projects focus on diversity across virus groups:
- Parvoviruses: Parvovirus-GLUE
- Flaviviruses: Flavivirus-GLUE
- Hepadnaviruses: Hepadnavirus-GLUE
- CRESS DNA viruses: CRESS-GLUE
- Filoviruses: Filovirus-GLUE
- Lentiviruses: Lentivirus-GLUE
- Deltaretroviruses: Deltaretrovirus-GLUE
Parvoviruses are a diverse group of small, non-enveloped DNA viruses that infect a wide variety of animal species, including many that are of significant medical and veterinary importance. The parvovirus family encompasses numerous pathogens affecting humans and domesticated animals, causing diseases such as canine parvoviral enteritis and parvovirus B19.
Beyond their role as pathogens, parvoviruses are also next-generation therapeutic tools. One group - the adeno-associated viruses (AAVs) - have been successfully developed as gene therapy vectors and are at the forefront of advancements in human gene therapy.
Parvovirus-GLUE was originally developed to support virus discovery and paleovirological investigations of the parvovirus 'fossil record'. The paleovirology components are contained within an extension layer. This layer connects to the gene therapy applications of parvoviruses, because the endogenous parvoviral element (EPV) loci mapped therein have been investigated as potential 'safe harbor' sites for targeted integration of AAV vectors.
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Comprehensive Genomic Database: Parvovirus-GLUE integrates a curated collection of parvovirus genome sequences from various species, providing a robust foundation for comparative genomics research.
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Standardized Data Formats: All genomic data, including sequences, alignments, and annotations, are standardized, ensuring consistency and interoperability across analyses.
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Standardization of the Virus Genome Coordinate Space: Parvovirus-GLUE includes fully annotated reference sequences for all known parvovirus species, providing a robust foundation for comparative research. All sequences use the coordinate space of a chosen reference sequence, maintaining consistency across analyses. Alignments constructed at distinct taxonomic levels are linked via a common set of reference sequences, facilitating genomic comparisons.
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Built for Comparative Genomics: Sequence data in Parvovirus-GLUE is organized in a phylogenetically-structured manner, allowing users to explore evolutionary relationships more completely. Richly annotated reference sequences enable rigorous comparative genomic analysis related to conservation, adaptation, structural context, and genotype-to-phenotype associations.
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Efficient and Reproducible Data Management: Parvovirus-GLUE enhances efficiency through the reuse of high-value data items, such as multiple sequence alignments, while ensuring reproducibility by providing a platform for sharing standardized analyses.
| Virus | Parvoviruses (family Parvoviridae) |
|---|---|
| Development Period | 2018-2024 |
| Lead Developers | Robert J. Gifford |
| Main Objectives | Comparative genomics |
| Data Sources | NCBI |
| Associated Tools | BLAST+, RAXML |
| Offline Access | GitHub |
| Status | Mature. Actively being developed |
| User Guide | GitHub Wiki |
Parvovirus-GLUE-EVE, which extends Parvovirus-GLUE through the incorporation of endogenous parvoviral elements.
Flavivirids (family Flaviviridae) are a group of positive-strand ribonucleic acid (RNA) viruses that pose serious risks to human and animal health on a global scale. These viruses are responsible for a wide range of diseases, including several that are transmitted by blood-feeding insects, and can lead to severe outbreaks, particularly in tropical and subtropical regions. Their impact is compounded by factors like climate change and global travel, making them a critical focus for public health efforts and scientific research.
Flavivirus-GLUE was developed to support the comparative genomic analysis of flavivirids, with a particular focus on paleovirological studies of endogenous viral elements (EVEs) derived from this group. Flaviviruses are ideal candidates for ecological and evolutionary research due to their global public health significance, diverse transmission routes, and wide geographical distribution. Their high mutation rates, rich genomic data, and importance in vaccine and drug development have driven extensive research into their evolution and ecology. Flavivirus-GLUE leverages these characteristics to facilitate deeper insights into flavivirus evolution, host-virus interactions, and viral persistence, while also providing a foundation for studying broader ecological and evolutionary patterns within this viral family.
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Comprehensive Genomic Database: Flavivirus-GLUE integrates a curated collection of flavivirid genome sequences from various species, providing a robust foundation for comparative genomics research.
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Standardized Data Formats: All genomic data, including sequences, alignments, and annotations, are standardized, ensuring consistency and interoperability across analyses.
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Relational Data Structure: The GLUE framework links sequences with complex metadata, allowing for rich, context-driven queries and analyses.
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Customizable Comparative Genomics Tools: Flavivirus-GLUE supports customizable genomic analyses tailored to specific research questions.
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Extensible Platform: Flavivirus-GLUE is highly extensible, allowing users to add their own data, annotations, and custom analysis tools, seamlessly integrating them into the core system.
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Reproducible Workflows: Designed to ensure reproducibility, Flavivirus-GLUE provides a platform for sharing standardized analyses, allowing for collaboration and transparent research practices.
| Virus | Flavivirids (family Flaviviridae) |
|---|---|
| Development Period | 2018-2022 |
| Lead Developers | Robert J. Gifford |
| Main Objectives | Comparative genomics |
| Data Sources | NCBI |
| Associated Tools | BLAST+, RAXML |
| Offline Access | GitHub |
| Status | Mature. Actively being developed |
| User Guide | GitHub Wiki |
Flavivirus-GLUE-EVE, which extends Flavivirus-GLUE through the incorporation of endogenous flaviviral elements.
Hepadnaviruses (family Hepadnaviridae) are a family of small, enveloped DNA viruses. They are unique among DNA viruses due to their replication process, which involves reverse transcription, a step more commonly associated with retroviruses. The most well-known member of this family is the hepatitis B virus (HBV), which causes hepatitis B in humans. HBV is estimated to infect ~300 million people worldwide, causing substantial morbidity and mortality. Recent studies have revealed that hepadnaviruses infect a diverse range of vertebrate species, ranging from fish to mammals. They are associated with disease in many of these species.
Hepadnavirus-GLUE is a specialized resource designed to facilitate comparative analysis of hepadnavirus genomes. It aims to provide researchers with tools to explore genetic diversity and functional genomics in a standardized, extensible environment. It was developed in the context of paleovirological investigations focussed on endogenous viral element (EVE) sequences derived from hepadnaviruses, often referred to as endogenous hepadnaviruses (eHBVs).
The study of eHBVs has been hindered not only by the degraded state of these sequences due to germline mutation, but also the circular hepadnavirus genome, which complicate the recovery of ancestral structures from eHBV insertions. Additional challenges arise from intra-genomic duplication and rearrangement, and the similarity between the hepadnaviral polymerase and reverse transcriptase genes of retroelements, which can obscure genomic interpretation.
Hepadnavirus-GLUE was developed to address these challenges by offering a novel, data-oriented approach. This resource not only compiles all relevant data—virus genome sequences, multiple sequence alignments, genome feature annotations, and other sequence-associated information—but also represents the semantic relationships between these data items. Through the GLUE engine, researchers can easily reproduce and build upon previous analyses, facilitating the study of eHBVs and enabling further comparative investigations across vertebrate species. This platform provides a robust foundation for advancing research into the evolutionary history and genomic impacts of hepadnaviruses.
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Comprehensive Genomic Database: Hepadnavirus-GLUE provides a robust foundation for comparative genomics research. It integrates a curated collection of hepadnavirus sequences from all known species and can be extended to incorporate sequences from endogenous hepadnaviruses.
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Standardized Data Formats: All genomic data, including sequences, alignments, and annotations, are standardized, ensuring consistency and interoperability across analyses.
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Relational Data Structure: The GLUE framework links sequences with complex metadata, allowing for rich, context-driven queries and analyses while minimizing manual pre-processing of datasets.
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Customizable Comparative Genomics Tools: Researchers can perform customizable genomic analyses, such as evolutionary studies, phylogenetic reconstruction, and genome feature comparisons, tailored to their specific research questions.
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Extensible Platform: The resource is highly extensible, allowing users to add their own data, annotations, and custom analysis tools, seamlessly integrating them into the core system.
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Reproducible Workflows: Designed to ensure reproducibility, Hepadnavirus-GLUE enables users to save and share their analyses, allowing for collaboration and transparent research practices.
| Virus | Hepadnaviruses (family Hepadnaviridae) |
|---|---|
| Development Period | 2018-Present |
| Lead Developers | Robert J. Gifford |
| Main Objectives | Comparative genomics |
| Data Sources | NCBI |
| Associated Tools | BLAST+, RAXML |
| Offline Access | GitHub |
| Status | Mature. Actively being developed |
| User Guide | GitHub Wiki |
Hepadnavirus-GLUE-EVE: extends Hepadnavirus-GLUE through the incorporation of endogenous hepadnaviral elements (eHBVs).
CRESS (circular rep-encoding single-stranded) DNA viruses are a diverse array of circular single-stranded DNA viruses. They have a broad host range, infecting animals, plants, fungi, diatoms, and other eukaryotes. They encompass circoviruses, geminiviruses, and nanoviruses, among others.
CRESS-GLUE is a specialized resource designed to support the comparative genomic analysis of circular Rep-encoding single-stranded DNA (CRESS DNA) viruses (phylum Cressdnaviricota). It was developed in the context of paleovirological investigations focussing on EVEs derived from this virus phylum.
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Comprehensive Genomic Database: CRESS-GLUE integrates a curated collection of CRESS DNA virus genome sequences from various species, providing a robust foundation for comparative genomics research.
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Standardized Data Formats: All genomic data, including sequences, alignments, and annotations, are standardized, ensuring consistency and interoperability across analyses. The resource includes fully annotated reference sequences for CRESS DNA virus species. All sequences use the coordinate space of a chosen reference sequence, maintaining consistency across analyses. Alignments constructed at distinct taxonomic levels are linked via a common set of reference sequences, facilitating genomic comparisons.
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Built for Comparative Genomics: Sequence data in CRESS-GLUE is organized in a phylogenetically-structured manner, allowing users to explore evolutionary relationships more completely. Richly annotated reference sequences enable rigorous comparative genomic analysis related to conservation, adaptation, structural context, and genotype-to-phenotype associations.
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Efficient and Reproducible Data Management: CRESS-GLUE enhances efficiency through the reuse of high-value data items, such as multiple sequence alignments, while ensuring reproducibility by providing a platform for sharing standardized analyses.
| Virus | CRESS DNA Viruses (phylum Cressdnaviricota) |
|---|---|
| Development Period | 2018-2021 |
| Lead Developers | Robert J. Gifford |
| Main Objectives | Comparative genomics |
| Data Sources | NCBI |
| Associated Tools | BLAST+, RAXML |
| Offline Access | GitHub |
| Status | Mature. Not currently being developed |
| User Guide | GitHub Wiki |
CRESS-GLUE-EVE: incorporates endogenous viral elements (EVEs) derived from CRESS DNA viruses.
The filoviruses (family Filoviridae) are enveloped, single-stranded RNA viruses known for their severe pathogenicity in humans and nonhuman primates. The two primary genera, Ebolavirus and Marburgvirus, include several species responsible for viral hemorrhagic fevers characterized by high mortality rates. Filoviruses are primarily zoonotic, with fruit bats and nonhuman primates identified as potential reservoirs. Transmission occurs through direct contact with infected bodily fluids or contaminated surfaces, leading to outbreaks that pose significant public health threats, particularly in sub-Saharan Africa.
EBOV-GLUE, a GLUE project for ebola virus (EBOV) was initially developed by Josh Singer ~2017. A GLUE project for all filoviruses was later developed by Rob Gifford and this project incorporated EBOV-GLUE. Filovirus-GLUE was developed in association with paleovirological investigations focussing on vertebrate genomes.
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Comprehensive Genomic Database: Filovirus-GLUE integrates a curated collection of filovirus genome sequences from various species, providing a robust foundation for comparative genomics research.
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Standardized Data Formats: All genomic data, including sequences, alignments, and annotations, are standardized, ensuring consistency and interoperability across analyses.
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Standardization of the Virus Genome Coordinate Space: Filovirus-GLUE includes fully annotated reference sequences for all known filovirus species, providing a robust foundation for comparative research. All sequences use the coordinate space of a chosen reference sequence, maintaining consistency across analyses. Alignments constructed at distinct taxonomic levels are linked via a common set of reference sequences, facilitating genomic comparisons.
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Built for Comparative Genomics: Sequence data in Filovirus-GLUE is organized in a phylogenetically-structured manner, allowing users to explore evolutionary relationships more completely. Richly annotated reference sequences enable rigorous comparative genomic analysis related to conservation, adaptation, structural context, and genotype-to-phenotype associations.
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Efficient and Reproducible Data Management: Filovirus-GLUE enhances efficiency through the reuse of high-value data items, such as multiple sequence alignments, while ensuring reproducibility by providing a platform for sharing standardized analyses.
| Virus | Filoviruses (family Filoviridae) |
|---|---|
| Development Period | 2018-2022 |
| Developers | Robert J. Gifford, Josh Singer |
| Main Objectives | Comparative genomics |
| Data Sources | NCBI |
| Associated Tools | BLAST+, RAXML |
| Offline Access | GitHub Link |
| Status | Mature. Not currently being developed |
| User Guide | GitHub Wiki |
Filovirus-GLUE-EVE: incorporates endogenous viral elements (EVEs) derived from filoviruses.
GLUE by Robert J. Gifford Lab.
For questions, issues, or feedback, please open an issue on the GitHub repository.