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Hidden genomic diversity of SARS-CoV-2: implications for qRT-PCR diagnostics and transmission

Nicolae Sapoval, Medhat Mahmoud, Michael D. Jochum, Yunxi Liu, R. A. Leo Elworth, Qi Wang, Dreycey Albin, Huw Ogilvie, Michael D. Lee, Sonia Villapol, Kyle M. Hernandez, Irina Maljkovic Berry, Jonathan Foox, Afshin Beheshti, Krista Ternus, Kjersti M. Aagaard, David Posada, View ORCID ProfileChristopher E. Mason, View ORCID ProfileFritz Sedlazeck, View ORCID ProfileTodd J. Treangen
doi: https://doi.org/10.1101/2020.07.02.184481
Nicolae Sapoval
1Department of Computer Science, Rice University, Houston, TX, USA
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Medhat Mahmoud
2Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX
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Michael D. Jochum
3Baylor College of Medicine and Texas Children’s Hospital, Houston, TX
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Yunxi Liu
1Department of Computer Science, Rice University, Houston, TX, USA
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R. A. Leo Elworth
1Department of Computer Science, Rice University, Houston, TX, USA
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Qi Wang
4Systems, Synthetic, and Physical Biology (SSPB) Graduate Program, Houston, TX
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Dreycey Albin
4Systems, Synthetic, and Physical Biology (SSPB) Graduate Program, Houston, TX
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Huw Ogilvie
1Department of Computer Science, Rice University, Houston, TX, USA
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Michael D. Lee
5Exobiology Branch, NASA Ames Research Center, Mountain View, CA
6Blue Marble Space Institute of Science, Seattle, WA
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Sonia Villapol
7Houston Methodist Research Institute, Houston, TX
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Kyle M. Hernandez
8Department of Medicine, University of Chicago, Chicago, IL
16Center for Translational Data Science, University of Chicago, Chicago, IL
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Irina Maljkovic Berry
9Walter Reed Army Institute of Research, Silver Spring, MD
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Jonathan Foox
10Department of Physiology and Biophysics, Weill Cornell Medicine, New York, New York
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Afshin Beheshti
11KBR, Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA
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Krista Ternus
12Signature Science, LLC, 8329 North Mopac Expressway, Austin TX 78759
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Kjersti M. Aagaard
3Baylor College of Medicine and Texas Children’s Hospital, Houston, TX
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David Posada
13Biomedical Research Center (CINBIO), University of Vigo, 36310 Vigo, Spain
14Department of Biochemistry, Genetics and Immunology School of Biology, University of Vigo, Vigo, Spain
15Galicia Sur Health Research Institute, 36310 Vigo, Spain
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Christopher E. Mason
10Department of Physiology and Biophysics, Weill Cornell Medicine, New York, New York
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  • ORCID record for Christopher E. Mason
Fritz Sedlazeck
2Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX
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Todd J. Treangen
1Department of Computer Science, Rice University, Houston, TX, USA
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  • For correspondence: treangen@rice.edu
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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 clades that have spread throughout the world. In this study, we investigated over 7,000 SARS-CoV-2 datasets to unveil both intrahost and interhost diversity. Our intrahost and interhost diversity analyses yielded three major observations. First, the mutational profile of SARS-CoV-2 highlights iSNV and SNP similarity, albeit with high variability in C>T 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 small indels fuel 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.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted July 02, 2020.
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Hidden genomic diversity of SARS-CoV-2: implications for qRT-PCR diagnostics and transmission
Nicolae Sapoval, Medhat Mahmoud, Michael D. Jochum, Yunxi Liu, R. A. Leo Elworth, Qi Wang, Dreycey Albin, Huw Ogilvie, Michael D. Lee, Sonia Villapol, Kyle M. Hernandez, Irina Maljkovic Berry, Jonathan Foox, Afshin Beheshti, Krista Ternus, Kjersti M. Aagaard, David Posada, Christopher E. Mason, Fritz Sedlazeck, Todd J. Treangen
bioRxiv 2020.07.02.184481; doi: https://doi.org/10.1101/2020.07.02.184481
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Hidden genomic diversity of SARS-CoV-2: implications for qRT-PCR diagnostics and transmission
Nicolae Sapoval, Medhat Mahmoud, Michael D. Jochum, Yunxi Liu, R. A. Leo Elworth, Qi Wang, Dreycey Albin, Huw Ogilvie, Michael D. Lee, Sonia Villapol, Kyle M. Hernandez, Irina Maljkovic Berry, Jonathan Foox, Afshin Beheshti, Krista Ternus, Kjersti M. Aagaard, David Posada, Christopher E. Mason, Fritz Sedlazeck, Todd J. Treangen
bioRxiv 2020.07.02.184481; doi: https://doi.org/10.1101/2020.07.02.184481

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