title: Viral quasispecies complexity measures.
abstract: Mutant spectrum dynamics (changes in the related mutants that compose viral populations) has a decisive impact on virus behavior. The several platforms of next generation sequencing (NGS) to study viral quasispecies offer a magnifying glass to study viral quasispecies complexity. Several parameters are available to quantify the complexity of mutant spectra, but they have limitations. Here we critically evaluate the information provided by several population diversity indices, and we propose the introduction of some new ones used in ecology. In particular we make a distinction between incidence, abundance and function measures of viral quasispecies composition. We suggest a multidimensional approach (complementary information contributed by adequately chosen indices), propose some guidelines, and illustrate the use of indices with a simple example. We apply the indices to three clinical samples of hepatitis C virus that display different population heterogeneity. Areas of virus biology in which population complexity plays a role are discussed.
authors.affiliation: Roche Diagnostics, Sant Cugat del Vallès, Spain; Liver Unit, Internal Medicine, Liver Disease Laboratory, Vall d'Hebron Institut Recerca-Hospital Universitari Vall d'Hebron (VHIR-HUVH), Universitat Autònoma de Barcelona, 08035 Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, 28029 Madrid, Spain. Electronic address: josep.gregori@vhir.org.
authors.forename: Josep
authors.initials: J
authors.lastname: Gregori
authors.affiliation: Liver Unit, Internal Medicine, Liver Disease Laboratory, Vall d'Hebron Institut Recerca-Hospital Universitari Vall d'Hebron (VHIR-HUVH), Universitat Autònoma de Barcelona, 08035 Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, 28029 Madrid, Spain; Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Campus de Cantoblanco, 28049 Madrid, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Perales
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, 28029 Madrid, Spain; Biochemistry Unit, Virology Unit, Microbiology Department, HUVH, 08035 Barcelona, Spain; Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Rodriguez-Frias
authors.affiliation: Liver Unit, Internal Medicine, Liver Disease Laboratory, Vall d'Hebron Institut Recerca-Hospital Universitari Vall d'Hebron (VHIR-HUVH), Universitat Autònoma de Barcelona, 08035 Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, 28029 Madrid, Spain; Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
authors.forename: Juan I
authors.initials: JI
authors.lastname: Esteban
authors.affiliation: Liver Unit, Internal Medicine, Liver Disease Laboratory, Vall d'Hebron Institut Recerca-Hospital Universitari Vall d'Hebron (VHIR-HUVH), Universitat Autònoma de Barcelona, 08035 Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, 28029 Madrid, Spain; Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Quer
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, 28029 Madrid, Spain; Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Campus de Cantoblanco, 28049 Madrid, Spain.
authors.forename: Esteban
authors.initials: E
authors.lastname: Domingo
mesh_terms: D044822:Biodiversity; D004463:Ecology / Q000379:methods; D016174:Hepacivirus / Q000145:classification; D006526:Hepatitis C / Q000821:virology; D006801:Humans; D015999:Multivariate Analysis; D013045:Species Specificity; D014780:Viruses / Q000145:classification*
keywords: Diversity indices; Gini-Simpson index; Hill numbers; Montserrat plots; Mutation frequency; Nucleotide diversity; Quasispecies profiles; Shannon entropy