b703c5f25fc3c92a5ca35e6a0fc6badd pmc_9739305.pdf 2cac0447b9d5e45dbb722cc0521f7a69dd6a827b pmc_9739305.pdf 9b25b5383e70a98dbb894a8de810905b9ffcae260fda238a13d5ba47494fd443 pmc_9739305.pdf Title: Quasispecies Fitness Partition to Characterize the Molecular Status of a Viral Population. Negative Effect of Early Ribavirin Discontinuation in a Chronically Infected HEV Patient Subject: The changes occurring in viral quasispecies populations during infection have been monitored using diversity indices, nucleotide diversity, and several other indices to summarize the quasispecies structure in a single value. In this study, we present a method to partition quasispecies haplotypes into four fractions according to their fitness: the master haplotype, rare haplotypes at two levels (those present at <0.1%, and those at 0.1–1%), and a fourth fraction that we term emerging haplotypes, present at frequencies >1%, but less than that of the master haplotype. We propose that by determining the changes occurring in the volume of the four quasispecies fitness fractions together with those of the Hill number profile we will be able to visualize and analyze the molecular changes in the composition of a quasispecies with time. To develop this concept, we used three data sets: a technical clone of the complete SARS-CoV-2 spike gene, a subset of data previously used in a study of rare haplotypes, and data from a clinical follow-up study of a patient chronically infected with HEV and treated with ribavirin. The viral response to ribavirin mutagenic treatment was selection of a rich set of synonymous haplotypes. The mutation spectrum was very complex at the nucleotide level, but at the protein (phenotypic/functional) level the pattern differed, showing a highly prevalent master phenotype. We discuss the putative implications of this observation in relation to mutagenic antiviral treatment. Keywords: quasispecies; deep-sequencing; variability; rare haplotypes; fitness; mutagens Author: Josep Gregori, Sergi Colomer-Castell, Carolina Campos, Marta Ibañez-Lligoña, Damir Garcia-Cehic, Ariadna Rando-Segura, Caroline Melanie Adombie, Rosa Pintó, Susanna Guix, Albert Bosch, Esteban Domingo, Isabel Gallego, Celia Perales, Maria Francesca Cortese, David Tabernero, Maria Buti, Mar Riveiro-Barciela, Juan Ignacio Esteban, Francisco Rodriguez-Frias and Josep Quer Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Nov 24 08:58:14 2022 CET ModDate: Thu Nov 24 09:04:38 2022 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 17 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2556678 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- SOZKOC+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 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Item: Title: Samples Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Processing the Sequencing Data Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Quasispecies Fitness Partitions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Hill Numbers Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Abundance Filter Effect on Haplotype Distribution Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Sample Size Dependence Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Distance between Quasispecies, Quasispecies Dendrograms, and Multidimensional Scale Plots (MDS) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Software and Statistics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Info: Title: Quasispecies Fitness Partition to Characterize the Molecular Status of a Viral Population. Negative Effect of Early Ribavirin Discontinuation in a Chronically Infected HEV Patient Author: Josep Gregori, Sergi Colomer-Castell, Carolina Campos, Marta Ibañez-Lligoña, Damir Garcia-Cehic, Ariadna Rando-Segura, Caroline Melanie Adombie, Rosa Pintó, Susanna Guix, Albert Bosch, Esteban Domingo, Isabel Gallego, Celia Perales, Maria Francesca Cortese, David Tabernero, Maria Buti, Mar Riveiro-Barciela, Juan Ignacio Esteban, Francisco Rodriguez-Frias and Josep Quer Subject: The changes occurring in viral quasispecies populations during infection have been monitored using diversity indices, nucleotide diversity, and several other indices to summarize the quasispecies structure in a single value. In this study, we present a method to partition quasispecies haplotypes into four fractions according to their fitness: the master haplotype, rare haplotypes at two levels (those present at <0.1%, and those at 0.1 1%), and a fourth fraction that we term emerging haplotypes, present at frequencies >1%, but less than that of the master haplotype. We propose that by determining the changes occurring in the volume of the four quasispecies fitness fractions together with those of the Hill number profile we will be able to visualize and analyze the molecular changes in the composition of a quasispecies with time. To develop this concept, we used three data sets: a technical clone of the complete SARS-CoV-2 spike gene, a subset of data previously used in a study of rare haplotypes, and data from a clinical follow-up study of a patient chronically infected with HEV and treated with ribavirin. The viral response to ribavirin mutagenic treatment was selection of a rich set of synonymous haplotypes. The mutation spectrum was very complex at the nucleotide level, but at the protein (phenotypic/functional) level the pattern differed, showing a highly prevalent master phenotype. We discuss the putative implications of this observation in relation to mutagenic antiviral treatment. 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