Welcome to the GitHub repository for AAV-Atlas, an atlas of AAV genetic variants!

AAV-Atlas is a sequence-oriented resource for comparative genomic analysis of adeno-associated viruses (AAVs), developed using the GLUE software framework.

AAVs are small, non-pathogenic DNA viruses widely used in gene therapy due to their tissue-specific targeting, long-term gene expression, and mild immunogenicity. They have enabled groundbreaking treatments for genetic diseases, such as Luxturna for inherited retinal disorders, Zolgensma for spinal muscular atrophy, and therapies for hemophilia. Despite challenges like limited packaging capacity and immune responses, ongoing advancements in capsid engineering and production methods are enhancing their therapeutic potential.

GLUE is an open, integrated software toolkit that provides functionality for storage and interpretation of sequence data. It provides an extensible platform for implementing 'sequence-based resources' that represent the semantic links between sequences and other data items via a relational database. This minimises the requirement for labour-intensive pre-processing of data, and allows sequence-based analyses to be implemented in an efficient, standardised and reproducible way.

AAV-Atlas provides a command line interface (CLI) and can be installed locally, opting either for a Docker-based or native installation.

Please see the User Guide for more details.

• GLUE Framework Integration: Built on the GLUE software framework, AAV-Atlas offers an extensible platform for efficient, standardized, and reproducible computational genomic analysis of AAV virus.

• Phylogenetic Structure: Sequence data in AAV-Atlas is organized in a phylogenetically-structured manner, allowing users to explore evolutionary relationships comprehensively.

• Rich Annotations: Annotated reference sequences enable rigorous comparative genomic analysis related to conservation, adaptation, structural context, and genotype-to-phenotype associations.

• Automated Genotyping: Includes functionality for assigning AAV sequences to groups and subgroups using maximum likelihood clade assignment (MLCA).

• Variant Mapping: Maps amino acid substitutions across all published AAV sequences, facilitating comparative analysis.

To install AAV-Atlas, follow the instructions provided in the User Guide.

You can choose between:

• Docker-based installation for ease of deployment.
• Native installation for traditional setup.

AAV-Atlas can be installed as a prebuilt database for quick setup or constructed from scratch for more customization.

GLUE contains an interactive command line environment focused on the development and use of GLUE projects by bioinformaticians. This provides a range of productivity-oriented features such as automatic command completion, command history and interactive paging through tabular data.

For detailed instructions on how to use AAV-Atlas for your comparative genomic analysis, refer to the GLUE's reference documentation.

AAV-Atlas includes a fully reproducible analysis pipeline used to investigating horizontal transfer of AAV capsid genes among rep lineages. This analysis is located in analyses/ht_analysis/

The directory contains:

• Phylogenetic trees based on different taxon and partition sets
• Imported EVEs and outgroups
• Re-rooting strategies and visualisation metadata
• Orthogonal support from tools like GARD and SplitsTree

For details, see the ht_analysis/README.md.

The AAV-Atlas project is organized as follows:

aav_atlas.sql.gz                    # Compressed SQL database dump (GLUE project)
alignments/                         # Saved alignment files
analyses/                           # Reproducible comparative analyses (e.g., HT analysis)
  └── ht_analysis/                  # Horizontal transfer analysis workflow, trees, metadata
buildAavAtlas.glue                  # Master script for building AAV-Atlas from source
example/                            # Example input/output files
glue/                               # Core project scripts and source data
  ├── aavBuildCoreProject.glue      # Script: Initialize core schema and data
  ├── aavBuildNuccoreExt.glue       # Script: Import NCBI nuccore sequences
  ├── aavImportSources.glue         # Script: Handle import of sequence sources
  ├── aavModules.glue               # Script: Register module definitions
  ├── aavProjectSettings.glue       # Script: Set general project config
  ├── aavSchemaExtensions.glue      # Script: Define schema extensions
  └── ...                           # Subdirectories contain inputs and logic for specific domains
md/                                 # Markdown documentation files
modules/                            # GLUE module configuration XMLs
  ├── aavMaxLikelihoodGenotyper.xml # MLCA genotyping module config
  ├── ...                           # Additional utility and analysis modules
README.md                           # Main project description and usage instructions
sources/                            # Raw input sequence data (e.g. GenBank FASTA)
tabular/                            # Tabular metadata / side-data
trees/                              # Stored phylogenetic tree files

AAV-Atlas is constructed using public data obtained from the NCBI Nucleotide database.

We welcome contributions from the community! If you're interested in contributing to AAV-Atlas, please review our Contribution Guidelines.

The project is licensed under the GNU Affero General Public License v. 3.0

For questions, issues, or feedback, please open an issue on the GitHub repository.

For collaboration please contact Dr Robert Gifford.