Evidence map›Paper›PMID 35745516›Full record

ArticlePathogens (Basel, Switzerland)2022

SARS-CoV-2 Mutant Spectra at Different Depth Levels Reveal an Overwhelming Abundance of Low Frequency Mutations.

Brenda Martínez-González, María Eugenia Soria, Lucía Vázquez-Sirvent, Cristina Ferrer-Orta, Rebeca Lobo-Vega, Pablo Mínguez, Lorena de la Fuente, Carlos Llorens, Beatriz Soriano, Ricardo Ramos-Ruíz and 22 more

Abstract read
In one paragraph

Article in Pathogens (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed.

  1. Article
  2. Article
  3. Methods to Characterize Mutant Spectra of RNA Viruses: The Case of SARS-CoV-2.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  4. SARS-CoV-2 mutant spectrum complexity is an epidemiologically evolvable trait.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  5. Article
  6. Review
  7. Review
  8. Point mutations at specific sites of the nsp12-nsp8 interface dramatically affect the RNA polymerization activity of SARS-CoV-2.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  9. Incipient functional SARS-CoV-2 diversification identified through neural network haplotype maps.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. The Mutational Landscape of SARS-CoV-2.International journal of molecular sciences · 2023
    Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

32 authors.

Brenda Martínez-GonzálezDepartment of Clinical Microbiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain.ORCID 0000-0002-4482-5181
María Eugenia SoriaDepartment of Clinical Microbiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain.ORCID 0000-0002-4719-3351
Lucía Vázquez-SirventDepartment of Clinical Microbiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain.
Cristina Ferrer-OrtaStructural Biology Department, Institut de Biología Molecular de Barcelona CSIC, 08028 Barcelona, Spain.
Rebeca Lobo-VegaDepartment of Clinical Microbiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain.ORCID 0000-0002-4882-6763
Pablo MínguezDepartment of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain.ORCID 0000-0003-4099-9421
Lorena de la FuenteDepartment of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain.
Carlos LlorensBiotechvana, "Scientific Park", Universidad de Valencia, 46980 Valencia, Spain.ORCID 0000-0003-1402-4743
Beatriz SorianoBiotechvana, "Scientific Park", Universidad de Valencia, 46980 Valencia, Spain.
Ricardo Ramos-RuízUnidad de Genómica, "Scientific Park of Madrid", Campus de Cantoblanco, 28049 Madrid, Spain.ORCID 0000-0002-6331-9786
Marta CortónDepartment of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain.ORCID 0000-0003-0087-1626
Rosario López-RodríguezDepartment of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain.
Carlos García-CrespoCentro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, 28049 Madrid, Spain.ORCID 0000-0001-6561-5389
Pilar SomovillaCentro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, 28049 Madrid, Spain.
Antoni Durán-PastorCentro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, 28049 Madrid, Spain.ORCID 0000-0002-4248-0554
Isabel GallegoCentro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, 28049 Madrid, Spain.
Ana Isabel de ÁvilaCentro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, 28049 Madrid, Spain.
Soledad DelgadoDepartamento de Sistemas Informáticos, Escuela Técnica Superior de Ingeniería de Sistemas Informáticos (ETSISI), Universidad Politécnica de Madrid, 28031 Madrid, Spain.ORCID 0000-0003-4868-3712
Federico MoránDepartamento de Bioquímica y Biología Molecular, Universidad Complutense de Madrid, 28005 Madrid, Spain.
Cecilio López-GalíndezUnidad de Virología Molecular, Laboratorio de Referencia e Investigación en Retrovirus, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, 28222 Madrid, Spain.ORCID 0000-0002-2324-9584
Jordi GómezCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain.
Luis EnjuanesDepartment of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, 28049 Madrid, Spain.ORCID 0000-0002-0854-0226
Llanos Salar-VidalDepartment of Clinical Microbiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain.ORCID 0000-0002-3052-0176
Mario Esteban-MuñozDepartment of Clinical Microbiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain.
Jaime EstebanDepartment of Clinical Microbiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain.ORCID 0000-0002-8971-3167
Ricardo Fernández-RoblasDepartment of Clinical Microbiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain.
Ignacio GadeaDepartment of Clinical Microbiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain.
Carmen AyusoDepartment of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain.ORCID 0000-0002-9242-7065
Javier Ruíz-HornillosAllergy Unit, Hospital Infanta Elena, Valdemoro, 28342 Madrid, Spain.
Nuria VerdaguerStructural Biology Department, Institut de Biología Molecular de Barcelona CSIC, 08028 Barcelona, Spain.ORCID 0000-0001-8826-7129
Esteban DomingoCentro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, 28049 Madrid, Spain.
Celia PeralesDepartment of Clinical Microbiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain.ORCID 0000-0003-1618-1937

Funding

Comunidad de Madrid PEJD-2019-PRE/BMD-16414Comunidad de Madrid S2018/BAA-4370Fundacio La Marato TV3 525/C/2021Instituto de Salud Carlos III COV20/00181Instituto de Salud Carlos III CP16/00116Instituto de Salud Carlos III CPII17/00006Instituto de Salud Carlos III CPII19/00001Instituto de Salud Carlos III PFIS FI19/00119Instituto de Salud Carlos III PI18/00210Instituto de Salud Carlos III PI21/00139Ministerio de Ciencia e Innovación PID2020-113888RB-I00Ministerio de Ciencia, Innovación y Universidades BFU2017-91384-EXPMinisterio de Ciencia, Innovación y Universidades PRE2018-083422Ministry of Economy, Industry and Competitiveness DI-17-09134Spanish National Research Council CSIC-COV19-014
6 · The paper itself

Abstract

Populations of RNA viruses are composed of complex and dynamic mixtures of variant genomes that are termed mutant spectra or mutant clouds. This applies also to SARS-CoV-2, and mutations that are detected at low frequency in an infected individual can be dominant (represented in the consensus sequence) in subsequent variants of interest or variants of concern. Here we briefly review the main conclusions of our work on mutant spectrum characterization of hepatitis C virus (HCV) and SARS-CoV-2 at the nucleotide and amino acid levels and address the following two new questions derived from previous results: (i) how is the SARS-CoV-2 mutant and deletion spectrum composition in diagnostic samples, when examined at progressively lower cut-off mutant frequency values in ultra-deep sequencing; (ii) how the frequency distribution of minority amino acid substitutions in SARS-CoV-2 compares with that of HCV sampled also from infected patients. The main conclusions are the following: (i) the number of different mutations found at low frequency in SARS-CoV-2 mutant spectra increases dramatically (50- to 100-fold) as the cut-off frequency for mutation detection is lowered from 0.5% to 0.1%, and (ii) that, contrary to HCV, SARS-CoV-2 mutant spectra exhibit a deficit of intermediate frequency amino acid substitutions. The possible origin and implications of mutant spectrum differences among RNA viruses are discussed.

Indexed as

COVID-19deletionmutationnsp12 (polymerase)RNA virusspikeultra-deep sequencingviral quasispecies

Identifiers

PMID35745516
PMCPMC9227345

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