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Expand Up @@ -21,7 +21,7 @@ <h2 class="project-tagline">Resources for comparative genomic analysis of parvov

<a href="./website/html/viruses.html" class="btn">Viruses</a>
<a href="./website/html/paleoviruses.html" class="btn">Paleoviruses</a>
<a href="./website/html/highlights.html" class="btn">Highlights</a>
<!--<a href="./website/html/highlights.html" class="btn">Highlights</a>-->
<!-- <a href="./website/html/tutorial.html" class="btn">Tutorial</a> -->
<a href="https://github.com/giffordlabcvr/Parvovirus-GLUE/zipball/master" class="btn">Download</a>
<a href="https://github.com/giffordlabcvr/Parvovirus-GLUE/tree/master" class="btn">GitHub</a>
Expand Down Expand Up @@ -82,343 +82,6 @@ <h3>
</blockquote>


<br>
<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>


<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>

<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>

<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>


<p><img src="./website/assets/images/github-hosting.jpg" alt="GitHub hosting figure"/></p>



<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>


<p>
<a target="_blank" href="http://glue-tools.cvr.gla.ac.uk/"><b>GLUE</b></a> is an open, integrated
software toolkit that provides functionality for storage and interpretation of
sequence data.
</p>

<p>
<b>GLUE</b> 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>


<p><img src="./website/assets/images/parvovirus-glue-project.jpg" alt="Parvovirus GLUE project figure"/></p>


<p>
Projects are loaded into the <b>GLUE "engine"</b>, creating a relational database
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>.
</p>


<p><img src="./website/assets/images/parvovirus-glue-usage.jpg" alt="Using Parvovirus GLUE"/></p>



<p>
The core schema of this database can be extended to accommodate
the idiosyncrasies of different projects, and
GLUE provides a scripting layer (based on JavaScript) for developing custom
analysis tools.
</p>

<p>
Some examples of '<b>sequence-based resources</b>' built for viruses using GLUE include:

</p>



<p>

<ul>

<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>

<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>

<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>

</ul>


</p>



<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 Parvovirus-GLUE project offer?</strong>
</h3>
<hr>



<p>

Parvovirus-GLUE offers a number of advantages for performing comparative sequence
analysis of parvoviruses:

<ol>

<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>

<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>


<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>

<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>

<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>

<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>

</ol>


</p>



<br>
<h3>
<a id="glueProject" class="anchor" href="#glueProject" aria-hidden="true"><span aria-hidden="true" class="octicon octicon-link"></span></a><strong>Building this GLUE project</strong>
</h3>
<hr>



<p>

On computers with the GLUE software framework
<a target="_blank" href="http://glue-tools.cvr.gla.ac.uk/#/installation"><b>installed</b></a>,
the <b>Parvovirus-GLUE</b> project can be instantiated by navigating to the project folder,
initiating GLUE, and issuing the following command in the GLUE shell:

<pre>
<code>Mode path: /
GLUE> run file buildCoreProject.glue</code></pre>

This will build the Parvovirus-GLUE core project by executing the commands in
<a href="https://github.com/giffordlabcvr/Parvovirus-GLUE/blob/master/buildCoreProject.glue"><b>this file</b></a>.

</p>

<p>
The core project comprises a
dataset designed to represent the phylum in a minimal way (i.e. by including
only one or a handful of annotated reference sequences for each major lineage).
</p>


<p>
We have also created genus-level, extension projects individual genera within the
subfamily <i>Parvovirinae</i>.
These extensions incorporate a more extensive set of species for this virus family.
Once the core project has been built, the parvoviridae extension project can be
constructed, by executing the commands in
<a href="https://github.com/giffordlabcvr/Parvovirus-GLUE/blob/master/buildGenusLevelProjects.glue"><b>this file</b></a>,
as follows.

<pre>
<code>Mode path: /
GLUE> run file buildGenusLevelProjects.glue</code></pre>

</p>
<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>

<p>

Campbell M, Loncar S, Gifford RJ, Kotin R, and RJ Gifford
<b>(2022)</b>
<br>
Comparative analysis reveals the long-term co-evolutionary history of parvoviruses and vertebrates.
<br>
<i>PLoS Biology</i>
<a href="https://doi.org/10.1371/journal.pbio.3001867">[view]</a>
<br>
<br>

Hildebrandt E, Penzes J, Gifford RJ, Agbandje-Mckenna M, and R Kotin
<b>(2020)</b>
<br>
Evolution of dependoparvoviruses across geological timescales – implications for design of AAV-based gene therapy vectors.
<br>
<i>Virus Evolution</i>
<a href="https://academic.oup.com/ve/article/doi/10.1093/ve/veaa043/5842153">[view]</a>
<br>
<br>

Pénzes JJ, de Souza WM, Agbandje-Mckenna M, and RJ Gifford
<b>(2019)</b>
<br>
An ancient lineage of highly divergent parvoviruses infects both vertebrate and invertebrate hosts.
<br>
<i>Viruses</i>
<a href="https://www.mdpi.com/1999-4915/11/6/525" target="_blank">[view]</a>
<br>
<br>

Callaway HM, Subramanian S, Urbina C, Barnard K, Dick R, Hafentein SL, Gifford RJ, and CR Parrish
<b>(2019)</b>
<br>
Examination and reconstruction of three ancient endogenous parvovirus capsid proteins in rodent genomes.
<br>
<i>Journal of Virology</i>
<a href="https://jvi.asm.org/content/93/6/e01542-18.long" target="_blank">[view]</a>
<br>
<br>

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>

Pénzes JJ, Marsile-Medun S, Agbandje-McKenna M, and RJ Gifford
<b>(2018)</b>
<br>
Endogenous amdoparvovirus-related elements reveal insights into the biology and evolution of vertebrate parvoviruses.
<br>
<i>Virus Evolution</i>
<a href="https://academic.oup.com/ve/article/4/2/vey026/5179240" target="_blank">[view]</a>
<br>
<br>

de Souza WM, Tristan TPW, Fumagalli MJ, Araujo J, Sabino-Santos Jr. G, Maia FGM, Acrani GO, Carrasco AOT, Romeiro MF, Modha S, Vieira LC, Ometto TL, Queiroz LH, Durigon EL, Nunes MRT, Figueiredo LTM, and RJ Gifford
<b>(2018)</b>
<br>
Whole-genome sequencing of parvoviruses from wild and domestic animals in Brazil provides new insights into parvovirus distribution and diversity.
<br>
<i>Viruses</i>
<a href="http://www.mdpi.com/1999-4915/10/4/143" target="_blank">[view]</a>

<br>
<br>
Souza WM, Romeiro MF, Fumagalli MJ, Modha S, de Araujo J, Queiroz LH, Durigon EL, Figueiredo LT, Murcia PR, Gifford RJ.
<b>(2017)</b>
<br>
Chapparvoviruses occur in at least three vertebrate classes and have a broad biogeographic distribution.
<br>
<i>J Gen Virol.</i>
<a href="http://jgv.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.000671" target="_blank">[view]</a>

</p>


<br>



<h3>
<a id="license" class="anchor" href="#license" aria-hidden="true"><span aria-hidden="true" class="octicon octicon-link"></span></a><strong>License</strong>
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2 changes: 1 addition & 1 deletion website/html/paleoviruses.html
View file
Original file line number Diff line number Diff line change
Expand Up @@ -21,7 +21,7 @@ <h2 class="project-tagline">Resources for comparative genomic analysis of parvov

<a href="../../index.html" class="btn">Home</a>
<a href="./viruses.html" class="btn">Viruses</a>
<a href="./highlights.html" class="btn">Highlights</a>
<!-- <a href="./highlights.html" class="btn">Highlights</a>-->
<!-- <a href="./tutorial.html" class="btn">Tutorial</a>-->
<a href="https://github.com/giffordlabcvr/Parvovirus-GLUE-EVE/zipball/master" class="btn">Download</a>
<a href="https://github.com/giffordlabcvr/Parvovirus-GLUE-EVE/tree/master" class="btn">GitHub</a>
Expand Down
2 changes: 1 addition & 1 deletion website/html/viruses.html
View file
Original file line number Diff line number Diff line change
Expand Up @@ -23,7 +23,7 @@ <h2 class="project-tagline">Resources for comparative genomic analysis of parvov
<a href="../../index.html" class="btn">Home</a>
<a href="./paleoviruses.html" class="btn">Paleoviruses</a>
<!-- <a href="./tutorial.html" class="btn">Tutorial</a>-->
<a href="./highlights.html" class="btn">Highlights</a>
<!-- <a href="./highlights.html" class="btn">Highlights</a>-->
<a href="https://github.com/giffordlabcvr/Parvovirus-GLUE/zipball/master" class="btn">Download</a>
<a href="https://github.com/giffordlabcvr/Parvovirus-GLUE/tree/master" class="btn">GitHub</a>

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