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Profiling SARS-CoV-2 mutation fingerprints that range from the viral pangenome to individual infection quasispecies

BACKGROUND: The genome of SARS-CoV-2 is susceptible to mutations during viral replication due to the errors generated by RNA-dependent RNA polymerases. These mutations enable the SARS-CoV-2 to evolve into new strains. Viral quasispecies emerge from de novo mutations that occur in individual patients...

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Autores principales: Lau, Billy T., Pavlichin, Dmitri, Hooker, Anna C., Almeda, Alison, Shin, Giwon, Chen, Jiamin, Sahoo, Malaya K., Huang, ChunHong, Pinsky, Benjamin A., Lee, HoJoon, Ji, Hanlee P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654905/
https://www.ncbi.nlm.nih.gov/pubmed/33173909
http://dx.doi.org/10.1101/2020.11.02.20224816
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author Lau, Billy T.
Pavlichin, Dmitri
Hooker, Anna C.
Almeda, Alison
Shin, Giwon
Chen, Jiamin
Sahoo, Malaya K.
Huang, ChunHong
Pinsky, Benjamin A.
Lee, HoJoon
Ji, Hanlee P.
author_facet Lau, Billy T.
Pavlichin, Dmitri
Hooker, Anna C.
Almeda, Alison
Shin, Giwon
Chen, Jiamin
Sahoo, Malaya K.
Huang, ChunHong
Pinsky, Benjamin A.
Lee, HoJoon
Ji, Hanlee P.
author_sort Lau, Billy T.
collection PubMed
description BACKGROUND: The genome of SARS-CoV-2 is susceptible to mutations during viral replication due to the errors generated by RNA-dependent RNA polymerases. These mutations enable the SARS-CoV-2 to evolve into new strains. Viral quasispecies emerge from de novo mutations that occur in individual patients. In combination, these sets of viral mutations provide distinct genetic fingerprints that reveal the patterns of transmission and have utility in contract tracing. METHODS: Leveraging thousands of sequenced SARS-CoV-2 genomes, we performed a viral pangenome analysis to identify conserved genomic sequences. We used a rapid and highly efficient computational approach that relies on k-mers, short tracts of sequence, instead of conventional sequence alignment. Using this method, we annotated viral mutation signatures that were associated with specific strains. Based on these highly conserved viral sequences, we developed a rapid and highly scalable targeted sequencing assay to identify mutations, detect quasispecies and identify mutation signatures from patients. These results were compared to the pangenome genetic fingerprints. RESULTS: We built a k-mer index for thousands of SARS-CoV-2 genomes and identified conserved genomics regions and landscape of mutations across thousands of virus genomes. We delineated mutation profiles spanning common genetic fingerprints (the combination of mutations in a viral assembly) and rare ones that occur in only small fraction of patients. We developed a targeted sequencing assay by selecting primers from the conserved viral genome regions to flank frequent mutations. Using a cohort of SARS-CoV-2 clinical samples, we identified genetic fingerprints consisting of strain-specific mutations seen across populations and de novo quasispecies mutations localized to individual infections. We compared the mutation profiles of viral samples undergoing analysis with the features of the pangenome. CONCLUSIONS: We conducted an analysis for viral mutation profiles that provide the basis of genetic fingerprints. Our study linked pangenome analysis with targeted deep sequenced SARS-CoV-2 clinical samples. We identified quasispecies mutations occurring within individual patients, mutations demarcating dominant species and the prevalence of mutation signatures, of which a significant number were relatively unique. Analysis of these genetic fingerprints may provide a way of conducting molecular contact tracing.
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spelling pubmed-76549052020-11-11 Profiling SARS-CoV-2 mutation fingerprints that range from the viral pangenome to individual infection quasispecies Lau, Billy T. Pavlichin, Dmitri Hooker, Anna C. Almeda, Alison Shin, Giwon Chen, Jiamin Sahoo, Malaya K. Huang, ChunHong Pinsky, Benjamin A. Lee, HoJoon Ji, Hanlee P. medRxiv Article BACKGROUND: The genome of SARS-CoV-2 is susceptible to mutations during viral replication due to the errors generated by RNA-dependent RNA polymerases. These mutations enable the SARS-CoV-2 to evolve into new strains. Viral quasispecies emerge from de novo mutations that occur in individual patients. In combination, these sets of viral mutations provide distinct genetic fingerprints that reveal the patterns of transmission and have utility in contract tracing. METHODS: Leveraging thousands of sequenced SARS-CoV-2 genomes, we performed a viral pangenome analysis to identify conserved genomic sequences. We used a rapid and highly efficient computational approach that relies on k-mers, short tracts of sequence, instead of conventional sequence alignment. Using this method, we annotated viral mutation signatures that were associated with specific strains. Based on these highly conserved viral sequences, we developed a rapid and highly scalable targeted sequencing assay to identify mutations, detect quasispecies and identify mutation signatures from patients. These results were compared to the pangenome genetic fingerprints. RESULTS: We built a k-mer index for thousands of SARS-CoV-2 genomes and identified conserved genomics regions and landscape of mutations across thousands of virus genomes. We delineated mutation profiles spanning common genetic fingerprints (the combination of mutations in a viral assembly) and rare ones that occur in only small fraction of patients. We developed a targeted sequencing assay by selecting primers from the conserved viral genome regions to flank frequent mutations. Using a cohort of SARS-CoV-2 clinical samples, we identified genetic fingerprints consisting of strain-specific mutations seen across populations and de novo quasispecies mutations localized to individual infections. We compared the mutation profiles of viral samples undergoing analysis with the features of the pangenome. CONCLUSIONS: We conducted an analysis for viral mutation profiles that provide the basis of genetic fingerprints. Our study linked pangenome analysis with targeted deep sequenced SARS-CoV-2 clinical samples. We identified quasispecies mutations occurring within individual patients, mutations demarcating dominant species and the prevalence of mutation signatures, of which a significant number were relatively unique. Analysis of these genetic fingerprints may provide a way of conducting molecular contact tracing. Cold Spring Harbor Laboratory 2020-11-04 /pmc/articles/PMC7654905/ /pubmed/33173909 http://dx.doi.org/10.1101/2020.11.02.20224816 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Lau, Billy T.
Pavlichin, Dmitri
Hooker, Anna C.
Almeda, Alison
Shin, Giwon
Chen, Jiamin
Sahoo, Malaya K.
Huang, ChunHong
Pinsky, Benjamin A.
Lee, HoJoon
Ji, Hanlee P.
Profiling SARS-CoV-2 mutation fingerprints that range from the viral pangenome to individual infection quasispecies
title Profiling SARS-CoV-2 mutation fingerprints that range from the viral pangenome to individual infection quasispecies
title_full Profiling SARS-CoV-2 mutation fingerprints that range from the viral pangenome to individual infection quasispecies
title_fullStr Profiling SARS-CoV-2 mutation fingerprints that range from the viral pangenome to individual infection quasispecies
title_full_unstemmed Profiling SARS-CoV-2 mutation fingerprints that range from the viral pangenome to individual infection quasispecies
title_short Profiling SARS-CoV-2 mutation fingerprints that range from the viral pangenome to individual infection quasispecies
title_sort profiling sars-cov-2 mutation fingerprints that range from the viral pangenome to individual infection quasispecies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654905/
https://www.ncbi.nlm.nih.gov/pubmed/33173909
http://dx.doi.org/10.1101/2020.11.02.20224816
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