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| <meta charset="UTF-8"> | ||
| <title>Flavivirus-GLUE by giffordlabcvr</title> | ||
| <meta name="viewport" content="width=device-width, initial-scale=1"> | ||
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| <link rel="stylesheet" type="text/css" href="website/assets/stylesheets/stylesheet.css" media="screen"> | ||
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| <body> | ||
| <section class="page-header"> | ||
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| <h1 class="project-name">Flavivirid-GLUE</h1> | ||
| <h2 class="project-tagline">Resources for comparative genomic analysis of flavivirids (family <i>Flaviviridae</i>)</h2> | ||
| <a href="./website/html/viruses.html" class="btn">Viruses</a> | ||
| <a href="./website/html/paleoviruses.html" class="btn">Paleoviruses</a> | ||
| <a href="./website/html/news.html" class="btn">News</a> | ||
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| <a href="https://github.com/giffordlabcvr/Flavivirus-GLUE/zipball/master" class="btn">Download</a> | ||
| <a target="_blank" href="https://github.com/giffordlabcvr/Flavivirus-GLUE/tree/master" class="btn">GitHub</a> | ||
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| </section> | ||
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| <section class="main-content"> | ||
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| <h3> | ||
| <a id="Background" class="anchor" href="#Background" aria-hidden="true"><span aria-hidden="true" class="octicon octicon-link"></span></a><strong>Comparative genomic analysis of flavivirids using GLUE</strong> | ||
| </h3> | ||
| <hr> | ||
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| <p> | ||
| This is <b>Flavivirid-GLUE</b>, a | ||
| <a target="_blank" href="http://glue-tools.cvr.gla.ac.uk/"><b>GLUE</b></a> | ||
| project for the | ||
| <a target="_blank" href="https://viralzone.expasy.org/43"><b>flavivirids</b></a> | ||
| (family <i>Flaviviridae</i>). | ||
| </p> | ||
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| <p> | ||
| The <i>Flaviviridae</i> comprise enveloped, positive-strand RNA viruses, | ||
| many of which pose serious risks to human health on a global scale. | ||
| Arthropod-borne flaviviruses such as Zika virus (<a target="_blank" href="https://www.cdc.gov/zika/index.html"><b>ZIKV</b></a>), | ||
| Dengue virus (<a target="_blank" href="https://www.cdc.gov/dengue/index.html"><b>DENV</b></a>), and | ||
| yellow fever virus (<a target="_blank" href="https://www.cdc.gov/yellowfever/index.html"><b>YFV</b></a>) | ||
| are the causative agents of large-scale outbreaks that result | ||
| in millions of human infections every year, while the bloodborne hepatitis C virus | ||
| (<a target="_blank" href="https://www.who.int/news-room/fact-sheets/detail/hepatitis-c"><b>HCV</b></a>) | ||
| is a major cause of chronic liver disease. | ||
| </p> | ||
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| <br> | ||
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| <p><img src="./website/assets/images/flavivirus-header.jpg" alt="Flaviviruses"/></p> | ||
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| <blockquote> | ||
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| <p> | ||
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| Projected urbanisation in 2027 (from <a target="_blank" href="https://www.economist.com/node/21642053">The Economist</a> magazine). | ||
| Urbanisation is often associated with the emergence and spread of mosquito-borne diseases | ||
| by creating favourable conditions for the survival of mosquito vector species. | ||
| Genome data can directly inform efforts to control diseases caused by mosquito-borne flaviviruses. | ||
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| </p> | ||
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| </blockquote> | ||
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| <br> | ||
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| <p> | ||
| Since the emergence of the SARS-COV2 pandemic, many have become familiar with | ||
| the use of <b>virus genome data</b> to track the spread and evolution of pathogenic viruses | ||
| - e.g. via tools such as <a target="_blank" href="https://nextstrain.org/ncov/gisaid/global""><b>NextStrain</b></a>. | ||
| However, it is less widely appreciated that the same kinds of data sets and comparative genomic approaches | ||
| can also be used to explore the structural and functional basis of virus adaptations. | ||
| </p> | ||
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| <p> | ||
| The <a target="_blank" href="https://github.com/giffordlabcvr/gluetools"><b>GLUE software framework</b></a> | ||
| provides an extensible platform for implementing computational genomic | ||
| analysis of viruses in an <b>efficient, standardised and reproducible</b> way. | ||
| <b>GLUE projects</b> can not only incorporate all of the data items typically used in | ||
| comparative genomic analysis | ||
| (e.g. sequences, alignments, genome feature annotations) but can also represent the complex | ||
| semantic links between these data items via a <b>relational database</b>. | ||
| This 'poises' sequences and associated data for application in computational | ||
| analysis, minimising the requirement for labour-intensive pre-processing of datasets. | ||
| </p> | ||
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| <p> | ||
| GLUE projects are equally suited for carrying out exploratory work | ||
| (e.g. using virus genome data to investigate structural and functional properties of viruses) | ||
| as they are for implementing operational procedures (e.g. producing | ||
| <a target="_blank" href="http://hcv-glue.cvr.gla.ac.uk/exampleReports/resistanceGeno1.html?hcvGlueVersion=0.1.68""><b>standardised reports</b></a> | ||
| in a public or animal health setting). | ||
| </p> | ||
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| <p> | ||
| Hosting of GLUE projects in an online version control system (e.g. <b>GitHub</b>) provides | ||
| a mechanism for their stable, collaborative development, as shown below. | ||
| </p> | ||
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| <p><img src="./website/assets/images/github-hosting.jpg" alt="GitHub illustration" /></p> | ||
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| <br> | ||
| <h3> | ||
| <a id="WhatGlueProject" class="anchor" href="#glueProject" aria-hidden="true"><span aria-hidden="true" class="octicon octicon-link"></span></a><strong>What is a GLUE project?</strong> | ||
| </h3> | ||
| <hr> | ||
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| <p> | ||
| <a target="_blank" href="https://github.com/giffordlabcvr/gluetools"><b>GLUE</b></a> is an open, integrated | ||
| software toolkit that provides functionality for storage and interpretation of | ||
| sequence data. It supports the development of <b>“projects”</b> containing the data items | ||
| required for comparative genomic analysis | ||
| (e.g. sequences, multiple sequence alignments, genome feature annotations, | ||
| and other sequence-associated data). | ||
| </p> | ||
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| <br> | ||
| <p><img src="./website/assets/images/glue-framework.jpg" alt="GLUE framework figure" /></p> | ||
| <br> | ||
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| <p> | ||
| Projects are loaded into the <b>GLUE "engine"</b>, creating a <b>relational database</b> | ||
| that represents the semantic relationships between data items. | ||
| This provides a robust foundation for the implementation of <b>systematic | ||
| comparative analyses</b> and the development of <b>sequence-based resources</b>. | ||
| The database schema can be extended to accommodate the idiosyncrasies of different projects. | ||
| GLUE provides a scripting layer (based on <a target="_blank" href="https://www.javascript.com/"><b>JavaScript</b></a>) | ||
| for developing custom analysis tools. | ||
| </p> | ||
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| <br> | ||
| <p><img src="./website/assets/images/glue-servers.png" alt="GLUE resources: server deployment illustration" /></p> | ||
| <br> | ||
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| <p> | ||
| Some examples of '<b>sequence-based resources</b>' built for viruses using GLUE include: | ||
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| </p> | ||
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| <br> | ||
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| <ul> | ||
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| <li> | ||
| <a target="_blank" href="http://cov-glue.cvr.gla.ac.uk/"><b>COV-GLUE</b></a>: | ||
| A GLUE resource for tracking genetic variation in SARS-COV2. | ||
| CoV-GLUE contains a database of amino acid replacements, insertions and | ||
| deletions which have been observed in GISAID hCoV-19 sequences sampled from the pandemic | ||
| </li> | ||
| <br> | ||
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| <li> | ||
| <a target="_blank" href="http://rabv-glue.cvr.gla.ac.uk/"><b>RABV-GLUE</b></a>: | ||
| Tailored toward epidemiological tracking of rabies virus (RABV). | ||
| Includes a database of RABV sequences and metadata from NCBI, updated daily and arranged into major and minor clades, and | ||
| an analysis tool providing genotyping, analysis and visualisation of submitted FASTA sequences. | ||
| </li> | ||
| <br> | ||
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| <li> | ||
| <a target="_blank" href="http://hcv-glue.cvr.gla.ac.uk/"><b>HCV-GLUE</b></a>: | ||
| This GLUE resource aims to support analysis of drug resistance and vaccine | ||
| escape in hepatitis C virus (HCV). | ||
| A database of HCV sequences and metadata from NCBI, updated daily and arranged | ||
| into clades (genotypes, subtypes). As well as pre-built multiple-sequence | ||
| alignments of NCBI sequences, it includes an analysis tool providing genotyping, | ||
| drug resistance analysis and visualisation of submitted FASTA sequences. | ||
| </li> | ||
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| </ul> | ||
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| </p> | ||
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| <br> | ||
| <h3> | ||
| <a id="WhyGlueProject" class="anchor" href="#glueProject" aria-hidden="true"><span aria-hidden="true" class="octicon octicon-link"></span></a><strong>What does building the Flavivirid-GLUE project offer?</strong> | ||
| </h3> | ||
| <hr> | ||
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| <p> | ||
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| <b>Flavivirid-GLUE</b> contains aligned, annotated reference genome sequences for all | ||
| <a href="./website/html/viruses.html">flavivirid</a> species and | ||
| <a href="./website/html/paleoviruses.html">endogenous viral elements (EVEs)</a> derived from flavivirids. | ||
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| It offers a number of advantages for performing comparative sequence | ||
| analysis of flavivirids: | ||
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| <ol> | ||
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| <li> <strong>Reproducibility</strong>. | ||
| For many reasons, bioinformatics analyses are notoriously difficult to reproduce. | ||
| The GLUE framework supports the implementation of fully reproducible | ||
| comparative genomics through the introduction of data standards and the use | ||
| of a relational database to capture the semantic links between data items. | ||
| </li> | ||
| <br> | ||
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| <li> <strong>Reusable data objects and analysis logic</strong>. | ||
| For many - if not most - comparative genomic analyses, data preparation is nine | ||
| tenths of the battle. The GLUE framework has been designed to ensure that | ||
| work spent preparing high-value data items such as multiple sequence alignments | ||
| need only be performed once. Hosting of GLUE projects in an online version control | ||
| system such as GitHub allows for collaborative management of important data items | ||
| and community testing of hypotheses. | ||
| </li> | ||
| <br> | ||
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| <li> <strong>Validation</strong>. | ||
| Building GLUE projects entails mapping the semantic links between data items | ||
| (e.g. sequences, tabular data, multiple sequence alignments). | ||
| This process provides an opportunity | ||
| for cross-validation, and thereby enforces a high level of data integrity. | ||
| </li> | ||
| <br> | ||
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| <li> <strong>Standardisation of the genomic co-ordinate space</strong>. GLUE | ||
| projects allow all sequences to utilise the coordinate space of a chosen | ||
| reference sequence. Contingencies associated with insertions and deletions | ||
| (indels) are handled in a systematic way. | ||
| </li> | ||
| <br> | ||
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| <li> <strong>Predefined, fully annotated reference sequences</strong>: | ||
| This project includes fully-annotated reference sequences for major lineages | ||
| within the <i>Hepadnaviridae</i> family. | ||
| </li> | ||
| <br> | ||
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| <li> <strong>Alignment trees</strong>: | ||
| GLUE allows linking of alignments constructed at distinct taxonomic levels | ||
| via an ""<b>alignment tree</b>" | ||
| data structure. In the alignment tree, each alignment | ||
| is constrained to a standard reference sequence, thus all multiple sequence | ||
| alignments are linked to one another via a standardised coordinate system. | ||
| </li> | ||
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| </ol> | ||
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| </p> | ||
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| <br> | ||
| <h3> | ||
| <a id="glueProject" class="anchor" href="#glueProject" aria-hidden="true"><span aria-hidden="true" class="octicon octicon-link"></span></a><strong>GLUE project</strong> | ||
| </h3> | ||
| <hr> | ||
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| <p> | ||
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| On computers with <a href="http://glue-tools.cvr.gla.ac.uk/#/installation">GLUE installed</a>, | ||
| the <b>Flavivirid-GLUE</b> project can be instantiated by navigating to the project folder, | ||
| initiating GLUE, and issuing the following command in the GLUE shell: | ||
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| <pre> | ||
| <code>Mode path: / | ||
| GLUE> run file buildCompleteProject.glue</code></pre> | ||
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| </p> | ||
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| <br> | ||
| <h3> | ||
| <a id="contributors" class="anchor" href="#contributors" aria-hidden="true"><span aria-hidden="true" class="octicon octicon-link"></span></a><strong>Contributors</strong> | ||
| </h3> | ||
| <hr> | ||
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| <p> | ||
| Robert J. Gifford (<a href="mailto:[email protected]">[email protected]</a>) | ||
| </p> | ||
| <p> | ||
| Rhys Parry | ||
| </p> | ||
| <p> | ||
| Connor Bamford | ||
| </p> | ||
| <p> | ||
| William Marciel de Souza | ||
| </p> | ||
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| <br> | ||
| <h3> | ||
| <a id="Publications" class="anchor" href="#Publications" aria-hidden="true"><span aria-hidden="true" class="octicon octicon-link"></span></a><strong>Related Publications</strong> | ||
| </h3> | ||
| <hr> | ||
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| <p> | ||
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| Bamford CGG, de Souza WM, Parry R and RJ Gifford | ||
| <b>(2021)</b> | ||
| <br> | ||
| Comparative analysis of genome-encoded viral sequences reveals the evolutionary history of the <i>Flaviviridae</i>. | ||
| <br> | ||
| <a href="https://www.biorxiv.org/content/10.1101/2021.09.19.460981v1" target="_blank">[preprint]</a> | ||
| <br> | ||
| <br> | ||
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| Singer JB, Thomson EC, McLauchlan J, Hughes J, and RJ Gifford | ||
| <b>(2018)</b> | ||
| <br> | ||
| GLUE: A flexible software system for virus sequence data. | ||
| <br> | ||
| <i>BMC Bioinformatics</i> | ||
| <a href="https://bmcbioinformatics.biomedcentral.com/articles/10.1186/s12859-018-2459-9" target="_blank">[view]</a> | ||
| <br> | ||
| <br> | ||
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| Zhu H, Dennis T, Hughes J, and RJ Gifford | ||
| <b>(2018)</b> | ||
| <br> | ||
| Database-integrated genome screening (DIGS): exploring genomes heuristically using sequence similarity search tools and a relational database. | ||
| <a href="https://www.biorxiv.org/content/early/2018/04/25/246835" target="_blank">[preprint]</a> | ||
| <br> | ||
| <br> | ||
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| </p> | ||
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| <h3> | ||
| <a id="license" class="anchor" href="#license" aria-hidden="true"><span aria-hidden="true" class="octicon octicon-link"></span></a><strong>License</strong> | ||
| </h3> | ||
| <hr> | ||
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| <p> | ||
| This project is licensed under the <a href="https://www.gnu.org/licenses/agpl-3.0.en.html">GNU Affero General Public License v. 3.0</a>. | ||
| </p> | ||
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| <br> | ||
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| <footer class="site-footer"> | ||
| <span class="site-footer-owner"><a href="https://github.com/giffordlabcvr/DIGS-tool">Flavivirid-GLUE</a> is maintained by <a href="https://github.com/giffordlabcvr">giffordlabcvr</a>.</span> | ||
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| <span class="site-footer-credits">This page was generated by <a href="https://pages.github.com">GitHub Pages</a> using the <a href="https://github.com/jasonlong/cayman-theme">Cayman theme</a> by <a href="https://twitter.com/jasonlong">Jason Long</a>.</span> | ||
| </footer> | ||
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