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

Another limitation of the current usage of VADR is that each model is built from a single RefSeq sequence. Valid sequences that are sufficiently dissimilar from all RefSeq-based models will fail because alerts designed to identify dissimilar sequences will be reported. The failures of some sequences from the test datasets that pass VAPiD and/or VIGOR can be attributed to this, as discussed in the Results section. During testing with incoming norovirus sequence submissions, three additional RefSeqs, included in the nine norovirus RefSeqs used for the tests described herein, were created to address this issue. Stimulated by some recent norovirus submissions with sequences dissimilar from the nine RefSeqs in the VADR 1.0 library and by a newly published norovirus genotyping paradigm [32] that suggested additional candidate RefSeqs more similar to the new sequences, we selected and curated 11 additional norovirus RefSeqs to reach a total of 20. Ten of the additional 11 RefSeqs are being tested on norovirus submissions since early 2020. VADR can be run on such sequences with 19 or 20 models for norovirus instead of nine models. Whichever ones of the additional 11 norovirus RefSeqs prove useful in internal testing will have their models included in a future released version of VADR and be used in automated processing of submissions.