Biological Sequence Quality Control and Organization

NIH Pandemic-Era Grants

Pandemic Era Grants

2021

Document text

Principal Investigator: Eric  Nawrocki
Organization: NATIONAL LIBRARY OF MEDICINE
Fiscal Year: 2021
Award: $187,304
Funding agency: National Library of Medicine

During the past year, we improved our software package VADR
(https://github.com/nawrockie/vadr) for viral sequence annotation
using models based on RefSeq annotation. VADR aligns complete input
sequences to their nearest RefSeq sequence and uses that alignment to
map the RefSeq annotation onto the input sequences. VADR is now being
used by GenBank to help annotate Norovirus, Dengue virus, SARS-CoV-2
and metazoan cytochrome C oxidase subunit 1 (COX1) protein-coding gene
sequences. 

Most of the development of VADR in the past year was aimed at
facilitating and improving validation and annotation of SARS-CoV-2
sequences. In December 2020, we added a new reference model for the
B.1.1.7 variant. In February 2021, we adapted the software to perform
less stringent quality checks on ORF8 after observing a relative large
number of validated mutations in that protein coding region (VADR
v1.1.3). In April 2021, we added a new model for the B.1.525 variant
and released v1.2 which accelerated sequence processing by about
10-fold and reduced the memory requirement about 30-fold to cope with
the increasing size of sequence submissions from state public health
labs and from the CDC. Finally, in August 2021, we released a new
version (v1.3) that reduced the stringency of quality checks on ORF3a,
ORF6, ORF7a, ORF7b and ORF10 to allow additional sequences without
problems in more essential coding regions (e.g. the spike coding
region) to pass VADR and be deposited into GenBank. Version 1.3 also
reports positional information related to all errors to enable users
to more easily investigate the reasons any of their sequences failed
VADR and were not deposited into GenBank.

In February 2021, we released a new version of the Ribovore software
package used for ribosomal RNA sequence analysis in various contexts
at GenBank (v1.0). We also submitted a paper on Ribovore to BMC
Bioinformatics which has been accepted but not yet published. To date,
the ribosensor program, which is part of Ribovore, has been used to
screen more than 50 million ribosomal RNA sequences submitted to
GenBank.

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