VADR: validation and annotation of virus sequence submissions to GenBank

Abstract

Background: GenBank contains over 3 million viral sequences. The National Center for Biotechnology Information (NCBI) previously made available a tool for validating and annotating influenza virus sequences that is used to check submissions to GenBank. Before this project, there was no analogous tool in use for non-influenza viral sequence submissions. Results: We developed a system called VADR (Viral Annotation DefineR) that validates and annotates viral sequences in GenBank submissions. The annotation system is based on analysis of the input nucleotide sequence using models built from curated RefSeqs. Hidden Markov models are used to classify sequences by determining the RefSeq they are most similar to, and feature annotation from the RefSeq is mapped based on a nucleotide alignment of the full sequence to a covariance model. Predicted proteins encoded by the sequence are validated with nucleotide-to-protein alignments using BLAST. The system identifies 43 types of "alerts" that (unlike the previous BLAST-based system) provide deterministic and rigorous feedback to researchers who submit sequences with unexpected characteristics. VADR has been integrated into GenBank's submission processing pipeline allowing for viral submissions passing all tests to be accepted and annotated automatically, without the need for any human (GenBank indexer) intervention. Unlike the previous submission-checking system, VADR is freely available (https://github.com/nawrockie/vadr) for local installation and use. VADR has been used for Norovirus submissions since May 2018 and for Dengue virus submissions since January 2019. Other viruses with high numbers of submissions will be added incrementally. Conclusion: VADR improves the speed with which non-flu virus submissions to GenBank can be checked and improves the content and quality of the GenBank annotations. The availability and portability of the software allows researchers to run the GenBank checks prior to submitting their viral sequences, and thereby gain confidence that their submissions will be accepted immediately without the need to correspond with GenBank staff. Reciprocally, the adoption of VADR frees GenBank staff to spend more time on services other than checking routine viral sequence submissions.

Computational strategies to combat COVID-19: useful tools to accelerate SARS-CoV-2 and coronavirus research

“…VADR validates and annotates viral sequences based on models built from reference sequences [ 85 ]. Coronavirus models, based on NCBI RefSeq [ 73 ] entries, including one for SARS-CoV-2 (NC_045512.2), are available for analyzing coronavirus sequences.…”

Computational Strategies to Combat COVID-19: Useful Tools to Accelerate SARS-CoV-2 and Coronavirus Research

“…VADR validates and annotates viral sequences based on models built from reference sequences [25]. 14 , tutorials, videos, a mailing list, and the dedicated wiki pages of the GitHub repository.…”

“…CORDITE integrates many functionalities to enable users to access, sort, and download relevant data to conduct meta-analyses, to design new clinical trials, or even to conduct a curated literature search. CORDITE automatically incorporates publications from PubMed 23 , bioRxiv 24 , chemRxiv 25 , and medRxiv 26 that report information on computational, in vitro, or case studies on potential drugs for COVID-19. Besides original research, reviews and comments are also included in the database.…”

“…https://www.ncbi.nlm.nih.gov/pubmed/24 https://www.biorxiv.org/25 https://www.chemrxiv.org/26 https://www.medrxiv.org/ 27 https://clinicaltrials.gov/…”

DBCOVP: A database of coronavirus virulent glycoproteins

“…A GenBank submissions tool, Viral Annotation DefineR (VADR, https://github.com/nawrockie/vadr ), was specifically designed to validate and annotate viral sequences. VADR has been used to check sequence submissions norovirus (May 2018), dengue virus (January 2019), and SARS-CoV-2 (March 2020) sequence submissions [ 30 ]. Likewise, the Viral Bioinformatics Resource Center (VBRC, https://4virology.net/ ) funded by the National Institute of Allergy and Infectious Diseases, holds information on curated viral genomes (belonging to the family Coronaviridae, Asfarviridae, Poxviridae) and a plethora of bioinformatics tools to perform genome analysis [ 31 ].…”