Viral Quasispecies Inference from Single Observations-Mutagens as Accelerators of Quasispecies Evolution
Gregori i Font, Josep (Vall d'Hebron Institut de Recerca (VHIR))
Salicrú, Miquel (Universitat de Barcelona)
Ibañez Lligoña, Marta (Vall d'Hebron Institut de Recerca (VHIR))
Colomer-Castell, Sergi (Vall d'Hebron Institut de Recerca (VHIR))
Campos, Carolina (Vall d'Hebron Institut de Recerca (VHIR))
González-Camuesco, Alvaro (Vall d'Hebron Institut de Recerca (VHIR))
Quer, Josep 1965- (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Data:	2025
Resum:	RNA virus populations exist as quasispecies-complex, dynamic clouds of closely related but genetically diverse variants generated by high mutation rates during replication. Assessing quasispecies structure and diversity is crucial for understanding viral evolution, adaptation, and response to antiviral treatments. However, comparing single quasispecies observations from individual biosamples, especially at different infection or treatment time points, presents statistical challenges. Traditional inferential tests are inapplicable due to the lack of replicate observations, and resampling-based approaches such as the bootstrap and jackknife are limited by biases and non-independence, particularly for diversity indices sensitive to rare haplotypes. In this study, we address these limitations by applying the delta method to derive analytical variances for a set of quasispecies structure indicators specifically designed to assess the quasispecies maturation state. We demonstrate the utility of this approach using high-depth next-generation sequencing data from hepatitis C virus (HCV) quasispecies evolving in vitro under various conditions, including free evolution and exposure to antiviral or mutagenic treatments. Our results reveal that with highly fit HCV quasispecies, sofosbuvir inhibits quasispecies genetic diversity, while mutagenic treatments accelerate maturation, compared to untreated controls. We emphasize the interpretation of results through absolute differences, log-fold changes, and standardized effect sizes, moving beyond mere statistical significance. This framework enables robust, quantitative comparisons of quasispecies diversity from single observations, providing valuable insights into viral adaptation and treatment response. The R code and session info with required libraries and versions is provided in the supplementary material.
Ajuts:	Instituto de Salud Carlos III PI22/00258 Agencia Estatal de Investigación PID2023-148013OB-C22 Generalitat de Catalunya 2021SGR01421 "la Caixa" Foundation LCF/BQ/DR23/12000020
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Inference ; Quasispecies ; Single-observation ; RNA-virus ; Mutagens ; Inhibitors
Publicat a:	Microorganisms, Vol. 13 (august 2025) , ISSN 2076-2607

DOI: 10.3390/microorganisms13092029
PMID: 41011360

15 p, 311.5 KB

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