VADR is a suite of tools for classifying and analyzing sequences homologous to a set of reference models of viral genomes or gene families. It has been mainly tested for analysis of Norovirus, Dengue, and SARS-CoV-2 virus sequences in preparation for submission to the GenBank database.
The VADR v-annotate.pl script is used to classify a sequence, by
determining which in a set of reference models it is most similar to,
and then annotate that sequence based on that most similar model.
Example usage of v-annotate.pl can be found
here. Another VADR script,
v-build.pl, is used to create the models from NCBI RefSeq sequences
or from input multiple sequence alignments, potentially with secondary
structure annotation. v-build.pl stores the RefSeq feature
annotation in the model, and v-annotate.pl maps that annotation
(e.g. CDS coordinates) onto the sequences it annotates. VADR includes
205 prebuilt models of Flaviviridae and Caliciviridae viral RefSeq
genomes, created with a process similar to the one described
here. Example usage of
v-build.pl can be found here. To use
v-annotate.pl with viruses other than the default set of 205, see
'Available VADR models'. For instructions on using VADR for
SARS-CoV-2 annotation see this
page.
v-annotate.pl identifies unexpected or divergent attributes of the
sequences it annotates (e.g. invalid or early stop codons in CDS
features) and reports them to the user in the form of alerts. A
subset of alerts are fatal and cause a sequence to fail. A
sequence passes if zero fatal alerts are reported for it. VADR is
used by GenBank staff to evaluate incoming sequence submissions of
some viruses (currently Norovirus, Dengue virus, and SARS-CoV-2.
Submitted Norovirus and Dengue virus sequences that pass
v-annotate.pl are accepted into GenBank.
The homology search and alignment components of VADR scripts, the most computationally expensive steps, are performed by the Infernal and BLAST software packages, which are downloaded and installed with VADR installation.
The v-annotate.pl script in VADR v1.1 has some enhancements
specifically designed for SARs-CoV-2 annotation that increase speed
(-s option) and provide better annotation for sequences with
stretches of Ns (-r option). See this
page
for more information on using VADR to annotate SARS-CoV-2 sequences.
VADR installation includes a default set of Flaviviridae and
Caliciviridae models including Norovirus and Dengue virus. You can
download additional pre-built models to use to validate and
annotate viruses, including SARS-CoV-2, or cox1 genes as listed
below. Importantly, to use a set of models other than the default set
that is installed with VADR, you will need to use either the --mdir
and --mkey options, or the the -m, -i, -x and possibly -n
options as described here.
Pre-built models are available for:
- SARS-CoV-2 (NC_045512) and other Coronaviridae RefSeqs
- Norovirus and Dengue virus RefSeqs, along with other Flaviviridae and Caliciviridae RefSeqs (this is the "default" set of models that is installed with VADR)
- metazoan Cytochrome c oxidase I (COX1)
See this page for more information
- VADR installation instructions
v-build.plexample usage and command-line optionsv-annotate.plexample usage, command-line options and alert information- VADR output file formats
- Available VADR model files (github wiki)
- SARS-CoV-2 annotation (github wiki)
- Development notes and instructions (github wiki)
- The recommended citation for using VADR is: Alejandro A Schaffer, Eneida L Hatcher, Linda Yankie, Lara Shonkwiler, J Rodney Brister, Ilene Karsch-Mizrachi, Eric P Nawrocki; VADR: validation and annotation of virus sequence submissions to GenBank; bioRxiv 852657; doi: https://doi.org/10.1101/852657. (This paper is currently in press at BMC Bioinformatics.)