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

doi:10.1101/2020.07.02.184481

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

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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.

Original language	English (US)
Journal	bioRxiv
DOIs	https://doi.org/10.1101/2020.07.02.184481
State	Unpublished - Jul 2 2020

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Sapoval, N., Mahmoud, M., Jochum, M. D., Liu, Y., Leo Elworth, R. A., Wang, Q., Albin, D., Ogilvie, H., Lee, M. D., Villapol, S., Hernandez, K. M., Berry, I. M., Foox, J., Beheshti, A., Ternus, K., Aagaard, K. M., Posada, D., Mason, C. E., Sedlazeck, F., & Treangen, T. J. (2020). Hidden genomic diversity of SARS-CoV-2: implications for qRT-PCR diagnostics and transmission. Unpublished. https://doi.org/10.1101/2020.07.02.184481

Sapoval, N, Mahmoud, M, Jochum, MD, Liu, Y, Leo Elworth, RA, Wang, Q, Albin, D, Ogilvie, H, Lee, MD, Villapol, S, Hernandez, KM, Berry, IM, Foox, J, Beheshti, A, Ternus, K, Aagaard, KM, Posada, D, Mason, CE, Sedlazeck, F & Treangen, TJ 2020, 'Hidden genomic diversity of SARS-CoV-2: implications for qRT-PCR diagnostics and transmission', bioRxiv. https://doi.org/10.1101/2020.07.02.184481

@article{3c86785da3864bbbb9fd1bb059146680,

title = "Hidden genomic diversity of SARS-CoV-2: 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 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.",

author = "Nicolae Sapoval and Medhat Mahmoud and Jochum, {Michael D} and Yunxi Liu and {Leo Elworth}, {R A} and Qi Wang and Dreycey Albin and Huw Ogilvie and Lee, {Michael D} and Sonia Villapol and Hernandez, {Kyle M} and Berry, {Irina Maljkovic} and Jonathan Foox and Afshin Beheshti and Krista Ternus and Aagaard, {Kjersti M} and David Posada and Mason, {Christopher E} and Fritz Sedlazeck and Treangen, {Todd J}",

year = "2020",

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doi = "10.1101/2020.07.02.184481",

language = "English (US)",

journal = "bioRxiv",

publisher = "Cold Spring Harbor Laboratory Press",

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TY - JOUR

T1 - Hidden genomic diversity of SARS-CoV-2

T2 - implications for qRT-PCR diagnostics and transmission

AU - Sapoval, Nicolae

AU - Mahmoud, Medhat

AU - Jochum, Michael D

AU - Liu, Yunxi

AU - Leo Elworth, R A

AU - Wang, Qi

AU - Albin, Dreycey

AU - Ogilvie, Huw

AU - Lee, Michael D

AU - Villapol, Sonia

AU - Hernandez, Kyle M

AU - Berry, Irina Maljkovic

AU - Foox, Jonathan

AU - Beheshti, Afshin

AU - Ternus, Krista

AU - Aagaard, Kjersti M

AU - Posada, David

AU - Mason, Christopher E

AU - Sedlazeck, Fritz

AU - Treangen, Todd J

PY - 2020/7/2

Y1 - 2020/7/2

N2 - 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.

AB - 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.

U2 - 10.1101/2020.07.02.184481

DO - 10.1101/2020.07.02.184481

M3 - Article

C2 - 32637955

JO - bioRxiv

JF - bioRxiv

ER -

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

Abstract

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