Modelling the Evolutionary Dynamics of Viruses within Their Hosts: A Case Study Using High-Throughput Sequencing
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{"title"=>"Modelling the evolutionary dynamics of viruses within their hosts: A case study using high-throughput sequencing", "type"=>"journal", "authors"=>[{"first_name"=>"Frédéric", "last_name"=>"Fabre", "scopus_author_id"=>"7006630128"}, {"first_name"=>"Josselin", "last_name"=>"Montarry", "scopus_author_id"=>"24449474900"}, {"first_name"=>"Jérôme", "last_name"=>"Coville", "scopus_author_id"=>"6603036201"}, {"first_name"=>"Rachid", "last_name"=>"Senoussi", "scopus_author_id"=>"56032256700"}, {"first_name"=>"Vincent", "last_name"=>"Simon", "scopus_author_id"=>"38862906800"}, {"first_name"=>"Benoît", "last_name"=>"Moury", "scopus_author_id"=>"6601981412"}], "year"=>2012, "source"=>"PLoS Pathogens", "identifiers"=>{"pui"=>"364837099", "issn"=>"15537366", "isbn"=>"1553-7374 (Electronic) 1553-7366 (Linking)", "doi"=>"10.1371/journal.ppat.1002654", "scopus"=>"2-s2.0-84861208697", "pmid"=>"22532800", "sgr"=>"84861208697"}, "id"=>"156a028f-96ec-30c5-9a59-f48f1c8bcef2", "abstract"=>"Uncovering how natural selection and genetic drift shape the evolutionary dynamics of virus populations within their hosts can pave the way to a better understanding of virus emergence. Mathematical models already play a leading role in these studies and are intended to predict future emergences. Here, using high-throughput sequencing, we analyzed the within-host population dynamics of four Potato virus Y (PVY) variants differing at most by two substitutions involved in pathogenicity properties. Model selection procedures were used to compare experimental results to six hypotheses regarding competitiveness and intensity of genetic drift experienced by viruses during host plant colonization. Results indicated that the frequencies of variants were well described using Lotka-Volterra models where the competition coefficients β(ij) exerted by variant j on variant i are equal to their fitness ratio, r(j)/r(i). Statistical inference allowed the estimation of the effect of each mutation on fitness, revealing slight (s = -0.45%) and high (s = -13.2%) fitness costs and a negative epistasis between them. Results also indicated that only 1 to 4 infectious units initiated the population of one apical leaf. The between-host variances of the variant frequencies were described using Dirichlet-multinomial distributions whose scale parameters, closely related to the fixation index F(ST), were shown to vary with time. The genetic differentiation of virus populations among plants increased from 0 to 10 days post-inoculation and then decreased until 35 days. Overall, this study showed that mathematical models can accurately describe both selection and genetic drift processes shaping the evolutionary dynamics of viruses within their hosts.", "link"=>"http://www.mendeley.com/research/modelling-evolutionary-dynamics-viruses-within-hosts-case-study-using-highthroughput-sequencing-5", "reader_count"=>62, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Researcher"=>23, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>18, "Student > Postgraduate"=>2, "Student > Master"=>5, "Other"=>1, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>4}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Researcher"=>23, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>18, "Student > Postgraduate"=>2, "Student > Master"=>5, "Other"=>1, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>4}, "reader_count_by_subject_area"=>{"Engineering"=>3, "Unspecified"=>5, "Environmental Science"=>2, "Biochemistry, Genetics and Molecular Biology"=>6, "Mathematics"=>1, "Agricultural and Biological Sciences"=>37, "Medicine and Dentistry"=>2, "Physics and Astronomy"=>1, "Chemical Engineering"=>1, "Social Sciences"=>2, "Computer Science"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>3}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Social Sciences"=>{"Social Sciences"=>2}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>37}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>6}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>5}, "Environmental Science"=>{"Environmental Science"=>2}, "Chemical Engineering"=>{"Chemical Engineering"=>1}}, "reader_count_by_country"=>{"United States"=>1, "Japan"=>1, "United Kingdom"=>2, "Slovenia"=>1, "France"=>1, "Chile"=>1, "India"=>1}, "group_count"=>5}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/650871"], "description"=>"<p><b>). </b><b>A</b>: Relative fitness of the four PVY variants (NN, NH, DN and DH) estimated by their intrinsic rates of increase <i>r</i>. The mean fitness of the population was arbitrarily set to 1 due to identifiability constraints (<a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002654#ppat.1002654.s004\" target=\"_blank\">Text S1</a>). In both graphs, dots indicate the mean values of the parameter whereas segments stand for the 95% confidence interval. Arrows indicate the most likely pathway leading to the resistance-breaking variant. <b>B</b>: <i>F</i><sub>ST</sub> indices as a function of time (dpi). <i>F</i><sub>ST</sub> characterizes the degree of genetic differentiation of the virus populations between plants. For each sampling date , was assessed as where is the scale parameter of a Dirichlet-multinomial distribution. For illustration purposes, a spline function (full line) is fitted to data.</p>", "links"=>[], "tags"=>["estimates", "supported"], "article_id"=>321360, "categories"=>["Virology", "Mathematics", "Biological Sciences", "Ecology", "Evolutionary Biology"], "users"=>["Frédéric Fabre", "Josselin Montarry", "Jérôme Coville", "Rachid Senoussi", "Vincent Simon", "Benoît Moury"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1002654.g003", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Parameter_estimates_of_the_model_that_is_best_supported_by_the_data_model_/321360", "title"=>"Parameter estimates of the model that is best supported by the data (model", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-19 00:22:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/334430", "https://ndownloader.figshare.com/files/334484", "https://ndownloader.figshare.com/files/334539", "https://ndownloader.figshare.com/files/334593", "https://ndownloader.figshare.com/files/334673"], "description"=>"<div><p>Uncovering how natural selection and genetic drift shape the evolutionary dynamics of virus populations within their hosts can pave the way to a better understanding of virus emergence. Mathematical models already play a leading role in these studies and are intended to predict future emergences. Here, using high-throughput sequencing, we analyzed the within-host population dynamics of four <em>Potato virus Y</em> (PVY) variants differing at most by two substitutions involved in pathogenicity properties. Model selection procedures were used to compare experimental results to six hypotheses regarding competitiveness and intensity of genetic drift experienced by viruses during host plant colonization. Results indicated that the frequencies of variants were well described using Lotka-Volterra models where the competition coefficients <em>β<sub>ij</sub></em> exerted by variant <em>j</em> on variant <em>i</em> are equal to their fitness ratio, <em>r<sub>j</sub></em>/<em>r<sub>i</sub></em>. Statistical inference allowed the estimation of the effect of each mutation on fitness, revealing slight (s = −0.45%) and high (s = −13.2%) fitness costs and a negative epistasis between them. Results also indicated that only 1 to 4 infectious units initiated the population of one apical leaf. The between-host variances of the variant frequencies were described using Dirichlet-multinomial distributions whose scale parameters, closely related to the fixation index <em>F</em><sub>ST</sub>, were shown to vary with time. The genetic differentiation of virus populations among plants increased from 0 to 10 days post-inoculation and then decreased until 35 days. Overall, this study showed that mathematical models can accurately describe both selection and genetic drift processes shaping the evolutionary dynamics of viruses within their hosts.</p> </div>", "links"=>[], "tags"=>["evolutionary", "viruses", "high-throughput", "sequencing"], "article_id"=>126069, "categories"=>["Mathematics", "Biological Sciences", "Cancer", "Ecology", "Evolutionary Biology"], "users"=>["Frédéric Fabre", "Josselin Montarry", "Jérôme Coville", "Rachid Senoussi", "Vincent Simon", "Benoît Moury"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1002654.s001", "https://dx.doi.org/10.1371/journal.ppat.1002654.s002", "https://dx.doi.org/10.1371/journal.ppat.1002654.s003", "https://dx.doi.org/10.1371/journal.ppat.1002654.s004", "https://dx.doi.org/10.1371/journal.ppat.1002654.s005"], "stats"=>{"downloads"=>6, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Modelling_the_Evolutionary_Dynamics_of_Viruses_within_Their_Hosts_A_Case_Study_Using_High_Throughput_Sequencing/126069", "title"=>"Modelling the Evolutionary Dynamics of Viruses within Their Hosts: A Case Study Using High-Throughput Sequencing", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-04-19 01:41:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/650776"], "description"=>"<p><b>). </b><b>A</b>: Correlation between the 20 (4 variants×5 dates) observed mean frequencies of the four PVY variants and their estimated mean values. <b>B</b>: Correlation between the 20 observed standard deviations of the frequencies of the four PVY variants and their estimated standard deviations. The full line is the first diagonal (<i>i.e.</i> line <i>y</i> = <i>x</i>).</p>", "links"=>[], "tags"=>["supported"], "article_id"=>321268, "categories"=>["Virology", "Mathematics", "Biological Sciences", "Ecology", "Evolutionary Biology"], "users"=>["Frédéric Fabre", "Josselin Montarry", "Jérôme Coville", "Rachid Senoussi", "Vincent Simon", "Benoît Moury"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1002654.g002", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Goodness_of_fit_of_the_model_that_is_best_supported_by_the_data_model_/321268", "title"=>"Goodness of fit of the model that is best supported by the data (model", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-19 00:21:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/650975"], "description"=>"a<p>Six models are obtained by crossing 2 hypotheses regarding the genetic differentiation of virus populations between plants (D<sub>1</sub> and D<sub>2</sub>) with 3 hypotheses regarding the competition issue between virus variants (C<sub>1</sub> to C<sub>3</sub>). They include four to 14 parameters and were compared using Akaike information criterion (AIC) and Bayesian information criterion (BIC) to identify the model that is best supported by the data.</p>b<p>The process of genetic differentiation of the virus populations between plants, described by the scale parameter <i>θ</i> of a Dirichlet-multinomial distribution, was allowed either to be constant (<i>θ<sup>s</sup></i> = <i>θ</i>) or time varying (, for the five sampling dates ).</p>c<p>The process of virus competition within plants included the intrinsic rates of variant increase (given that ) as parameters but might undergo one of three hypotheses specifying the type of Lotka-Volterra competition coefficients .</p>d<p>−2log(Likelihood).</p>", "links"=>[], "tags"=>["Virology", "ecology", "Computational biology", "Evolutionary biology", "mathematics"], "article_id"=>321460, "categories"=>["Virology", "Mathematics", "Biological Sciences", "Ecology", "Evolutionary Biology"], "users"=>["Frédéric Fabre", "Josselin Montarry", "Jérôme Coville", "Rachid Senoussi", "Vincent Simon", "Benoît Moury"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1002654.t001", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Models_description_and_selection_criteria_/321460", "title"=>"Models description and selection criteria.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-04-19 00:24:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/650628"], "description"=>"<p><b>A</b>: Description of the four PVY variants used (NN, NH, DN and DH). Variants are named according to the amino acids at positions 119 and 121 of the VPg pathogenicity factor. All variants infect the pepper genotype Yolo Wonder (YW) but only DH infects the genotype Florida VR2 which carries the <i>pvr2<sup>2</sup></i> resistance gene. <b>B–F</b>: Frequencies of the four PVY variants in the eight plant samples collected 6, 10, 15, 24 and 35 dpi. Additionally, for each date, a bar with the mean frequencies of the variants for the eight samples is provided. <b>G</b>: Mean (± standard deviation) frequencies of the four PVY variants as a function of time (dpi). <b>H</b>: Standard deviation of the frequencies of the four PVY variants as a function of time (dpi).</p>", "links"=>[], "tags"=>["intra-host", "pvy"], "article_id"=>321119, "categories"=>["Virology", "Mathematics", "Biological Sciences", "Ecology", "Evolutionary Biology"], "users"=>["Frédéric Fabre", "Josselin Montarry", "Jérôme Coville", "Rachid Senoussi", "Vincent Simon", "Benoît Moury"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1002654.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Observed_intra_host_dynamics_of_four_PVY_variants_/321119", "title"=>"Observed intra-host dynamics of four PVY variants.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-19 00:18:39"}

PMC Usage Stats | Further Information

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Relative Metric

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