VADR: validation and annotation of virus sequence submissions to GenBank

Alejandro A Schäffer; Eneida Hatcher; Linda Yankie; Lara Shonkwiler; J Rodney Brister; Ilene Karsch-Mizrachi; Eric P Nawrocki

VADR compares each input sequence to a library of homology models of viral species built from reference sequences from the RefSeq database [12] , identifies the most similar model, and uses that model to compute an alignment to the RefSeq from which feature annotation boundaries (e.g. coding sequences (denoted CDS), mature peptides, ncRNAs) are derived. Finally, CDS features that encode proteins are validated for protein-coding potential using blastx. Submitted sequences that are confidently aligned and annotated with VADR pass and are cleared for automatic entry into GenBank. In contrast, when a submitted sequence is evaluated by VADR and the comparison to its matching RefSeq reveals the input sequence is divergent in various ways (e.g. early stop codon, regions of low nucleotide similarity), then the sequence fails. Failure means that the sequence is flagged for manual review by an NCBI expert curator, called a "GenBank indexer", and the sequence is prevented from automatic entry into GenBank. If all sequences in a submission pass, all sequences will automatically be deposited into GenBank. If at least one sequence fails, a report with sequence-specific errors is generated and reported to the submitter or reviewed by the indexer, who can clear sequences for submission or contact the submitter for further investigation of the apparent problems.