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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 &lt;0.1%, and those at 0.1\u20131%), and a fourth fraction that we term emerging haplotypes, present at frequencies &gt;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.<\/jats:p>","DOI":"10.3390\/ijms232314654","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T03:24:09Z","timestamp":1669260249000},"page":"14654","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Quasispecies Fitness Partition to Characterize the Molecular Status of a Viral Population. 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[1st ed.]."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1093\/bioinformatics\/btt768","article-title":"Inference with viral quasispecies diversity indices: Clonal and NGS approaches","volume":"30","author":"Gregori","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.virol.2016.03.017","article-title":"Viral quasispecies complexity measures","volume":"493","author":"Gregori","year":"2016","journal-title":"Virology"},{"key":"ref_5","first-page":"139.e5","article-title":"Influence of treatment with neutralizing monoclonal antibodies on the SARS-CoV-2 nasopharyngeal load and quasispecies","volume":"28","author":"Vellas","year":"2022","journal-title":"Clin. Microbiol. Infect. Off. Publ. Eur. Soc. Clin. Microbiol. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.jmb.2004.10.066","article-title":"Monitoring sequence space as a test for the target of selection in viruses","volume":"345","author":"Perales","year":"2005","journal-title":"J. Mol. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Gregori, J., Soria, M.E., Gallego, I., Guerrero-Murillo, M., Esteban, J.I., Quer, J., Perales, C., and Domingo, E. (2018). Rare haplotype load as marker for lethal mutagenesis. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0204877"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.4155\/fmc-2018-0457","article-title":"The increasing impact of lethal mutagenesis of viruses","volume":"11","author":"Perales","year":"2019","journal-title":"Future Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s13577-017-0168-8","article-title":"Advantages of genome sequencing by long-read sequencer using SMRT technology in medical area","volume":"30","author":"Nakano","year":"2017","journal-title":"Hum. Cell"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Bull, R.A., Eltahla, A.A., Rodrigo, C., Koekkoek, S.M., Walker, M., Pirozyan, M.R., Betz-Stablein, B., Toepfer, A., Laird, M., and Oh, S. (2016). A method for near full-length amplification and sequencing for six hepatitis C virus genotypes. BMC Genom., 17.","DOI":"10.1186\/s12864-016-2575-8"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e129","DOI":"10.1093\/nar\/gkv630","article-title":"Multiplexed highly-accurate DNA sequencing of closely-related HIV-1 variants using continuous long reads from single molecule, real-time sequencing","volume":"43","author":"Dilernia","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"lqab019","DOI":"10.1093\/nargab\/lqab019","article-title":"Sequencing error profiles of Illumina sequencing instruments","volume":"3","author":"Stoler","year":"2021","journal-title":"NAR Genom. Bioinforma."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s13059-020-1935-5","article-title":"Opportunities and challenges in long-read sequencing data analysis","volume":"21","author":"Amarasinghe","year":"2020","journal-title":"Genome Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1038\/s41587-019-0217-9","article-title":"Accurate circular consensus long-read sequencing improves variant detection and assembly of a human genome","volume":"37","author":"Wenger","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"427","DOI":"10.2307\/1934352","article-title":"Diversity and Evenness: A Unifying Notation and Its Consequences","volume":"54","author":"Hill","year":"1973","journal-title":"Ecology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"11756","DOI":"10.1021\/acs.est.1c03589","article-title":"Monitoring Emergence of the SARS-CoV-2 B.1.1.7 Variant through the Spanish National SARS-CoV-2 Wastewater Surveillance System (VATar COVID-19)","volume":"55","author":"Carcereny","year":"2021","journal-title":"Environ. Sci. Technol."},{"key":"ref_17","unstructured":"(2022, November 12). Twist Synthetic SARS-CoV-2 RNA Control 2 MN908947.3. Available online: https:\/\/www.twistbioscience.com\/es\/resources\/product-sheet\/twist-synthetic-sars-cov-2-rna-controls."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1111\/liv.12362","article-title":"Identification of host and viral factors involved in a dissimilar resolution of a hepatitis C virus infection","volume":"34","author":"Cubero","year":"2014","journal-title":"Liver Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1093\/bioinformatics\/17.1.16","article-title":"PAQ: Partition Analysis of Quasispecies","volume":"17","author":"Baccam","year":"2001","journal-title":"Bioinformatics"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"T\u00f6pfer, A., Marschall, T., Bull, R.A., Luciani, F., Sch\u00f6nhuth, A., and Beerenwinkel, N. (2014). Viral quasispecies assembly via maximal clique enumeration. PLoS Comput. Biol., 10.","DOI":"10.1371\/journal.pcbi.1003515"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1093\/bioinformatics\/btx402","article-title":"QUENTIN: Reconstruction of disease transmissions from viral quasispecies genomic data","volume":"34","author":"Skums","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"i23","DOI":"10.1093\/bioinformatics\/bty291","article-title":"Viral quasispecies reconstruction via tensor factorization with successive read removal","volume":"34","author":"Ahn","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"vez028","DOI":"10.1093\/ve\/vez028","article-title":"DISSEQT-DIStribution-based modeling of SEQuence space Time dynamics","volume":"5","author":"Henningsson","year":"2019","journal-title":"Virus Evol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.coviro.2011.07.008","article-title":"Ultra-deep sequencing for the analysis of viral populations","volume":"1","author":"Beerenwinkel","year":"2011","journal-title":"Curr.Opin.Virol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lorenzo-Redondo, R., Delgado, S., Mor\u00e1n, F., and Lopez-Galindez, C. (2014). Realistic three dimensional fitness landscapes generated by self organizing maps for the analysis of experimental HIV-1 evolution. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0088579"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e0145921","DOI":"10.1128\/Spectrum.01459-21","article-title":"A Two-Level, Intramutant Spectrum Haplotype Profile of Hepatitis C Virus Revealed by Self-Organized Maps","volume":"9","author":"Delgado","year":"2021","journal-title":"Microbiol. Spectr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1080\/22221751.2021.1969868","article-title":"Host-dependent editing of SARS-CoV-2 in COVID-19 patients","volume":"10","author":"Gregori","year":"2021","journal-title":"Emerg. Microbes Infect."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Gonz\u00e1lez, B., Soria, M.E., V\u00e1zquez-Sirvent, L., Ferrer-Orta, C., Lobo-Vega, R., M\u00ednguez, P., de la Fuente, L., Llorens, C., Soriano, B., and Ramos-Ru\u00edz, R. (2022). SARS-CoV-2 Mutant Spectra at Different Depth Levels Reveal an Overwhelming Abundance of Low Frequency Mutations. Pathogens, 11.","DOI":"10.3390\/pathogens11060662"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"De Avila, A.I., Gallego, I., Soria, M.E., Gregori, J., Quer, J., Ignacio Esteban, J., Rice, C.M., Domingo, E., and Perales, C. (2016). Lethal mutagenesis of hepatitis C virus induced by favipiravir. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0164691"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Perales, C., Agudo, R., Tejero, H., Manrubia, S.C., and Domingo, E. (2009). Potential benefits of sequential inhibitor-mutagen treatments of RNA virus infections. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000658"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"11779322221085076","DOI":"10.1177\/11779322221085077","article-title":"Molnupiravir Does Not Induce Mutagenesis in Host Lung Cells during SARS-CoV-2 Treatment","volume":"16","author":"Githaka","year":"2022","journal-title":"Bioinform. Biol. Insights"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"100770","DOI":"10.1016\/j.jbc.2021.100770","article-title":"Molnupiravir promotes SARS-CoV-2 mutagenesis via the RNA template","volume":"297","author":"Gordon","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1097\/00001432-200112000-00015","article-title":"The mechanism of action of ribavirin: Lethal mutagenesis of RNA virus genomes mediated by the viral RNA-dependent RNA polymerase","volume":"14","author":"Cameron","year":"2001","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6172","DOI":"10.1128\/JVI.02778-12","article-title":"Deep sequencing reveals mutagenic effects of ribavirin during monotherapy of hepatitis C virus genotype 1-infected patients","volume":"87","author":"Dietz","year":"2013","journal-title":"J. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5760","DOI":"10.1128\/JVI.00201-09","article-title":"Effect of ribavirin on the mutation rate and spectrum of hepatitis C virus in vivo","volume":"83","author":"Cuevas","year":"2009","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.coviro.2018.10.001","article-title":"Hepatitis E virus treatment and ribavirin therapy: Viral mechanisms of nonresponse","volume":"32","author":"Todt","year":"2018","journal-title":"Curr. Opin. Virol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1136\/gutjnl-2015-311000","article-title":"In vivo evidence for ribavirin-induced mutagenesis of the hepatitis E virus genome","volume":"65","author":"Todt","year":"2016","journal-title":"Gut"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1053\/j.gastro.2014.08.040","article-title":"A mutation in the hepatitis E virus RNA polymerase promotes its replication and associates with ribavirin treatment failure in organ transplant recipients","volume":"147","author":"Debing","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1128\/AAC.02496-15","article-title":"Mutation in the Hepatitis E Virus Polymerase and Outcome of Ribavirin Therapy","volume":"60","author":"Lhomme","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.jhep.2016.05.002","article-title":"Hepatitis E virus mutations associated with ribavirin treatment failure result in altered viral fitness and ribavirin sensitivity","volume":"65","author":"Debing","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_41","unstructured":"(2022, November 12). ARTIC Network. Available online: https:\/\/artic.network\/ncov-2019."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1080\/22221751.2020.1806735","article-title":"Naturally occurring SARS-CoV-2 gene deletions close to the spike S1\/S2 cleavage site in the viral quasispecies of COVID19 patients","volume":"9","author":"Gregori","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.virol.2018.07.030","article-title":"Resistance of high fitness hepatitis C virus to lethal mutagenesis","volume":"523","author":"Gallego","year":"2018","journal-title":"Virology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3786","DOI":"10.1128\/AAC.00581-16","article-title":"Barrier-independent, fitness-associated differences in sofosbuvir efficacy against hepatitis c virus","volume":"60","author":"Gallego","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1002\/hep.22550","article-title":"Cell culture-produced hepatitis C virus does not infect peripheral blood mononuclear cells","volume":"48","author":"Marukian","year":"2008","journal-title":"Hepatology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"7593","DOI":"10.1128\/JVI.02824-12","article-title":"Response of hepatitis C virus to long-term passage in the presence of alpha interferon: Multiple mutations and a common phenotype","volume":"87","author":"Perales","year":"2013","journal-title":"J. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e02505-16","DOI":"10.1128\/JVI.02505-16","article-title":"Internal Disequilibria and Phenotypic Diversification during Replication of Hepatitis C Virus in a Noncoevolving Cellular Environment","volume":"91","author":"Moreno","year":"2017","journal-title":"J. Virol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2957","DOI":"10.1093\/bioinformatics\/btr507","article-title":"FLASH: Fast length adjustment of short reads to improve genome assemblies","volume":"27","author":"Magoc","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1890\/13-0133.1","article-title":"Rarefaction and extrapolation with Hill numbers: A framework for sampling and estimation in species diversity studies","volume":"84","author":"Chao","year":"2014","journal-title":"Ecol. Monogr."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Gregori, J., Esteban, J.I., Cubero, M., Garcia-Cehic, D., Perales, C., Casillas, R., Alvarez-Tejado, M., Rodriguez-Frias, F., Guardia, J., and Domingo, E. (2013). Ultra-deep pyrosequencing (UDPS) data treatment to study amplicon HCV minor variants. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0083361"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Nei, M. (1987). Molecular Evolutionary Genetics, Columbia University Press.","DOI":"10.7312\/nei-92038"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1093\/bioinformatics\/18.11.1523","article-title":"V Euclidian space and grouping of biological objects","volume":"18","author":"Grishin","year":"2002","journal-title":"Bioinformatics"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0022-2836(66)80258-9","article-title":"An improved method of testing for evolutionary homology","volume":"16","author":"Fitch","year":"1966","journal-title":"J. Mol. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1126\/science.185.4154.862","article-title":"Amino acid difference formula to help explain protein evolution","volume":"185","author":"Grantham","year":"1974","journal-title":"Science"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1080\/STA-200066418","article-title":"A Similarity Measure Based on Species Proportions","volume":"34","author":"Yue","year":"2005","journal-title":"Commun. Stat.-Theory Methods"},{"key":"ref_56","unstructured":"R Core Team (2019). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing."},{"key":"ref_57","unstructured":"Pages, H., Aboyoun, P., Gentleman, R., and DebRoy, S. (2022, November 12). Biostrings: String Objects Representing Biological Sequences, and Matching Algorithms, R package 2.38.4; 2012. Available online: https:\/\/bioc.ism.ac.jp\/packages\/3.2\/bioc\/html\/Biostrings.html."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1093\/bioinformatics\/btp450","article-title":"ShortRead: A bioconductor package for input, quality assessment and exploration of high-throughput sequence data","volume":"25","author":"Morgan","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_59","unstructured":"Guerrero-Murillo, M., and Gregori, J. (2022, November 22). QSutils: Quasispecies Diversity. R Package Version 1.0.0. Available online: https:\/\/bioconductor.org\/packages\/release\/bioc\/html\/QSutils.html_2018."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"R80","DOI":"10.1186\/gb-2004-5-10-r80","article-title":"Bioconductor: Open software development for computational biology and bioinformatics","volume":"5","author":"Gentleman","year":"2004","journal-title":"Genome Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1093\/bioinformatics\/bty633","article-title":"ape 5.0: An environment for modern phylogenetics and evolutionary analyses in R","volume":"35","author":"Paradis","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Wickham, H. (2019). Welcome to Master the Tidyverse. J. Open Source Softw., 4.","DOI":"10.21105\/joss.01686"},{"key":"ref_63","first-page":"1","article-title":"ggplot2: Elegant Graphics for Data Analysis","volume":"35","year":"2010","journal-title":"J. Stat. Soft. Book Rev."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/23\/14654\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:25:45Z","timestamp":1760145945000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/23\/14654"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,24]]},"references-count":63,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232314654"],"URL":"https:\/\/doi.org\/10.3390\/ijms232314654","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,24]]}}}