title: Quantification of HTLV-1 clonality and TCR diversity.
abstract: Estimation of immunological and microbiological diversity is vital to our understanding of infection and the immune response. For instance, what is the diversity of the T cell repertoire? These questions are partially addressed by high-throughput sequencing techniques that enable identification of immunological and microbiological "species" in a sample. Estimators of the number of unseen species are needed to estimate population diversity from sample diversity. Here we test five widely used non-parametric estimators, and develop and validate a novel method, DivE, to estimate species richness and distribution. We used three independent datasets: (i) viral populations from subjects infected with human T-lymphotropic virus type 1; (ii) T cell antigen receptor clonotype repertoires; and (iii) microbial data from infant faecal samples. When applied to datasets with rarefaction curves that did not plateau, existing estimators systematically increased with sample size. In contrast, DivE consistently and accurately estimated diversity for all datasets. We identify conditions that limit the application of DivE. We also show that DivE can be used to accurately estimate the underlying population frequency distribution. We have developed a novel method that is significantly more accurate than commonly used biodiversity estimators in microbiological and immunological populations.
authors.affiliation: Section of Immunology, Wright-Fleming Institute, Imperial College School of Medicine, London, United Kingdom.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Laydon
authors.affiliation: Section of Immunology, Wright-Fleming Institute, Imperial College School of Medicine, London, United Kingdom.
authors.forename: Anat
authors.initials: A
authors.lastname: Melamed
authors.affiliation: Centre for Integrative Systems Biology and Bioinformatics, South Kensington Campus, Imperial College, London, United Kingdom.
authors.forename: Aaron
authors.initials: A
authors.lastname: Sim
authors.affiliation: Section of Immunology, Wright-Fleming Institute, Imperial College School of Medicine, London, United Kingdom; Department of Molecular and Cellular Epigenetics, University of Liège, Liège, Belgium.
authors.forename: Nicolas A
authors.initials: NA
authors.lastname: Gillet
authors.affiliation: Section of Paediatrics, Wright-Fleming Institute, Imperial College School of Medicine, London, United Kingdom.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Sim
authors.affiliation: Vaccine Research Center, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Sam
authors.initials: S
authors.lastname: Darko
authors.affiliation: Section of Paediatrics, Wright-Fleming Institute, Imperial College School of Medicine, London, United Kingdom.
authors.forename: J Simon
authors.initials: JS
authors.lastname: Kroll
authors.affiliation: Vaccine Research Center, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
authors.affiliation: Vaccine Research Center, National Institutes of Health, Bethesda, Maryland, United States of America; Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, Wales, United Kingdom.
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.affiliation: Section of Immunology, Wright-Fleming Institute, Imperial College School of Medicine, London, United Kingdom.
authors.forename: Charles R M
authors.initials: CR
authors.lastname: Bangham
authors.affiliation: Section of Immunology, Wright-Fleming Institute, Imperial College School of Medicine, London, United Kingdom.
authors.forename: Becca
authors.initials: B
authors.lastname: Asquith
mesh_terms: D000465:Algorithms; D019295:Computational Biology; D030541:Databases, Genetic / Q000706:statistics & numerical data; D005243:Feces / Q000382:microbiology; D014644:Genetic Variation; D015490:HTLV-I Infections / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D007223:Infant; D064307:Microbiota / Q000235:genetics; D008957:Models, Genetic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D012623:Seawater / Q000382:microbiology; D018709:Statistics, Nonparametric
chemical_list: D011948:Receptors, Antigen, T-Cell