@article{3c8a62ddbca442708e59ed4c8a3b09b5,
title = "SARS-CoV-2 genomic diversity and the implications for qRT-PCR diagnostics and transmission",
abstract = "The COVID-19 pandemic has sparked an urgent need to uncover the underlying biology of this devastating disease. Though RNA viruses mutate more rapidly than DNA viruses, there are a relatively small number of single nucleotide polymorphisms (SNPs) that differentiate the main SARS-CoV-2 lineages that have spread throughout the world. In this study, we investigated 129 RNA-seq data sets and 6928 consensus genomes to contrast the intra-host and inter-host diversity of SARS-CoV-2. Our analyses yielded three major observations. First, the mutational profile of SARS-CoV-2 highlights intra-host single nucleotide variant (iSNV) and SNP similarity, albeit with differences in C > U changes. Second, iSNV and SNP patterns in SARS-CoV-2 are more similar to MERS-CoV than SARS-CoV-1. Third, a significant fraction of insertions and deletions contribute to the genetic diversity of SARS-CoV-2. Altogether, our findings provide insight into SARS-CoV-2 genomic diversity, inform the design of detection tests, and highlight the potential of iSNVs for tracking the transmission of SARS-CoV-2.",
keywords = "COVID-19/diagnosis, Genetic Variation, Genome, Viral, Host-Pathogen Interactions, Humans, Polymorphism, Single Nucleotide, Real-Time Polymerase Chain Reaction/methods, SARS-CoV-2/genetics",
author = "Nicolae Sapoval and Medhat Mahmoud and Jochum, {Michael D.} and Yunxi Liu and Elworth, {R. A.Leo} and Qi Wang and Dreycey Albin and Ogilvie, {Huw A.} and Lee, {Michael D.} and Sonia Villapol and Hernandez, {Kyle M.} and {Maljkovic Berry}, Irina and Jonathan Foox and Afshin Beheshti and Krista Ternus and Aagaard, {Kjersti M.} and David Posada and Mason, {Christopher E.} and Sedlazeck, {Fritz J.} and Treangen, {Todd J.}",
note = "Funding Information: The authors thank Jamie Purcell for feedback and discussion contributions on the effects of variants on the qRT-PCR detection methods. The authors also thank Dr. Luay Nakhleh for suggestions specific to comparative genomic analyses of SARS-CoV-1 and MERS-COV. The authors thank the GISAID contributors who provided the SARS-CoV-2 assemblies. Finally, the authors also thank all members of the COVID-19 International Research Team (www.cov-irt.org) for their helpful feedback during weekly meetings. N.S. and Y.L. are supported by the Department of Computer Science, Rice University. D.A., Q.W., N.S., R.A.L.E., T.J.T., and Y.L. are supported by startup funds from Rice University. N.S. and T.J.T. are partially supported by a C3.ai Digital Transformation Institute COVID-19 award (C3.ai DTI). M.D.J. is supported under National Institutes of Health (NIH) award No. R01HD091731 from the National Institute of Child Health and Human Development. F.J.S. acknowledges funding and part of the data was produced by Baylor College of Medicine under the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (U19AI144297-01). A.B. is supported by supplemental funds for COVID-19 research from Translational Research Institute for Space Health through National Aeronautics and Space Administration Cooperative Agreement NNX16AO69A (T-0404) and further funding was provided by KBR, Inc. D.P. is supported by the European Research Council (ERC-617457-PHYLOCANCER), Spanish Ministry of Economy and Competitiveness (PID2019-106247GB-I00), Fondo Supera COVID19 (EPICOVIGAL), and Xunta de Galicia (CT850A-2). This material has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation and/or publication. The views and conclusions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Army, Department of the Navy, Department of Defense, Office of the Director of National Intelligence, Army Research Office, or U.S. Government. Publisher Copyright: {\textcopyright} 2021 Sapoval et al. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = apr,
day = "1",
doi = "10.1101/gr.268961.120",
language = "English (US)",
volume = "31",
pages = "635--644",
journal = "Genome Research",
issn = "1088-9051",
publisher = "Cold Spring Harbor Laboratory Press",
number = "4",
}