Discrimination of Influenza Infection (A/2009 H1N1) from Prior Exposure by Antibody Protein Microarray Analysis
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{"title"=>"Discrimination of influenza infection (A/2009 H1N1) from prior exposure by antibody protein microarray analysis", "type"=>"journal", "authors"=>[{"first_name"=>"Dennis", "last_name"=>"Te Beest", "scopus_author_id"=>"35796485700"}, {"first_name"=>"Erwin", "last_name"=>"De Bruin", "scopus_author_id"=>"7004058831"}, {"first_name"=>"Sandra", "last_name"=>"Imholz", "scopus_author_id"=>"7801631471"}, {"first_name"=>"Jacco", "last_name"=>"Wallinga", "scopus_author_id"=>"7003807945"}, {"first_name"=>"Peter", "last_name"=>"Teunis", "scopus_author_id"=>"7003781978"}, {"first_name"=>"Marion", "last_name"=>"Koopmans", "scopus_author_id"=>"7006736989"}, {"first_name"=>"Michiel", "last_name"=>"Van Boven", "scopus_author_id"=>"7004419934"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"600550364", "sgr"=>"84913568733", "pmid"=>"25405997", "scopus"=>"2-s2.0-84913568733", "isbn"=>"1932-6203 (Electronic); 1932-6203 (Linking)", "doi"=>"10.1371/journal.pone.0113021", "issn"=>"19326203"}, "id"=>"390ecaee-eeac-3871-812e-b9d5c0e859b7", "abstract"=>"Reliable discrimination of recent influenza A infection from previous exposure using hemagglutination inhibition (HI) or virus neutralization tests is currently not feasible. This is due to low sensitivity of the tests and the interference of antibody responses generated by previous infections. Here we investigate the diagnostic characteristics of a newly developed antibody (HA1) protein microarray using data from cross-sectional serological studies carried out before and after the pandemic of 2009. The data are analysed by mixture models, providing a probabilistic classification of sera (susceptible, prior-exposed, recently infected). Estimated sensitivity and specificity for identifying A/2009 infections are low using HI (66% and 51%), and high when using A/2009 microarray data alone or together with A/1918 microarray data (96% and 95%). As a heuristic, a high A/2009 to A/1918 antibody ratio (>1.05) is indicative of recent infection, while a low ratio is indicative of a pre-existing response, even if the A/2009 titer is high. We conclude that highly sensitive and specific classification of individual sera is possible using the protein microarray, thereby enabling precise estimation of age-specific infection attack rates in the population even if sample sizes are small.", "link"=>"http://www.mendeley.com/research/discrimination-influenza-infection-a2009-h1n1-prior-exposure-antibody-protein-microarray-analysis", "reader_count"=>14, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>6, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>2, "Student > Master"=>2, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>6, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>2, "Student > Master"=>2, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1, "Mathematics"=>1, "Agricultural and Biological Sciences"=>6, "Medicine and Dentistry"=>1, "Immunology and Microbiology"=>4, "Economics, Econometrics and Finance"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>4}, "Economics, Econometrics and Finance"=>{"Economics, Econometrics and Finance"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>6}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Mathematics"=>{"Mathematics"=>1}}, "reader_count_by_country"=>{"Vietnam"=>2}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1799685"], "description"=>"<p>Data are stratified by study and age group (5–9, 10–19, 20–44, and 45–65 years). The bottom left corner in each panel shows the number of samples that tested negative in both assays. The top right corner shows Kendall's tau, a nonparametric correlation coefficient.</p>", "links"=>[], "tags"=>["classification", "sensitivity", "hi", "sample sizes", "ha", "data", "1N", "infection attack rates", "ratio", "Mixture Models", "Antibody Protein Microarray Analysis Reliable discrimination", "sera", "hemagglutination inhibition", "antibody responses", "influenza infection", "protein microarray", "virus neutralization tests"], "article_id"=>1246048, "categories"=>["Biological Sciences"], "users"=>["Dennis te Beest", "Erwin de Bruin", "Sandra Imholz", "Jacco Wallinga", "Peter Teunis", "Marion Koopmans", "Michiel van Boven"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0113021.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Standardised_hemagglutination_inhibition_titers_as_a_function_of_A_2009_microarray_titers_/1246048", "title"=>"Standardised hemagglutination inhibition titers as a function of A/2009 microarray titers.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-18 05:07:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/1799686"], "description"=>"<p>The data are aggregated as follows: <20, 20–40, 40–80, 80–160, 160–320, and 320–640. Grey and red bars represent pre- and post-pandemic data, respectively. The solid and dashed line represent the immune and infected component distribution, respectively. The cumulative probabilty density of the mixtures below the detection limit of 20 are marked with black dots.</p>", "links"=>[], "tags"=>["classification", "sensitivity", "hi", "sample sizes", "ha", "data", "1N", "infection attack rates", "ratio", "Mixture Models", "Antibody Protein Microarray Analysis Reliable discrimination", "sera", "hemagglutination inhibition", "antibody responses", "influenza infection", "protein microarray", "virus neutralization tests"], "article_id"=>1246049, "categories"=>["Biological Sciences"], "users"=>["Dennis te Beest", "Erwin de Bruin", "Sandra Imholz", "Jacco Wallinga", "Peter Teunis", "Marion Koopmans", "Michiel van Boven"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0113021.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_2009_H1N1_microarray_titers_bars_and_the_fitted_mixture_distributions_lines_/1246049", "title"=>"A/2009 (H1N1) microarray titers (bars) and the fitted mixture distributions (lines).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-18 05:07:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/1799687"], "description"=>"<p>Black and red dots represent the data, i.e. pre- and post-pandemic samples. Contours indicate the densities of the immune and infected distributions weighted by the the estimated age-specific infection probabilities (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0113021#pone-0113021-t003\" target=\"_blank\">Table 3</a>). The blue dots indicate that multiple samples are negative to both A/1918 and A/2009 (age-specific numbers in the pre-pandemic survey: 15, 20, 16, 19; post-pandemic survey: 9, 19, 19, 17). Grey areas indicate the regions with high probabilty that a post-pandemic sample is infected with A/2009. The susceptible component is placed largely placed beneath the detection limit and is not displayed.</p>", "links"=>[], "tags"=>["classification", "sensitivity", "hi", "sample sizes", "ha", "data", "1N", "infection attack rates", "ratio", "Mixture Models", "Antibody Protein Microarray Analysis Reliable discrimination", "sera", "hemagglutination inhibition", "antibody responses", "influenza infection", "protein microarray", "virus neutralization tests"], "article_id"=>1246050, "categories"=>["Biological Sciences"], "users"=>["Dennis te Beest", "Erwin de Bruin", "Sandra Imholz", "Jacco Wallinga", "Peter Teunis", "Marion Koopmans", "Michiel van Boven"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0113021.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Model_fit_of_bivariate_H1N1_microarray_data_A_2009_versus_A_1918_/1246050", "title"=>"Model fit of bivariate H1N1 microarray data (A/2009 versus A/1918).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-18 05:07:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/1799688"], "description"=>"<p>Shown are the estimated probabilty of infection in the univariate mixture (dots and solid line) with associated 95% confidence envelope (shaded area), and for each sample the corresponding estimates in the bivariate mixture (triangles) with associated 95% confidence intervals (bars).</p>", "links"=>[], "tags"=>["classification", "sensitivity", "hi", "sample sizes", "ha", "data", "1N", "infection attack rates", "ratio", "Mixture Models", "Antibody Protein Microarray Analysis Reliable discrimination", "sera", "hemagglutination inhibition", "antibody responses", "influenza infection", "protein microarray", "virus neutralization tests"], "article_id"=>1246051, "categories"=>["Biological Sciences"], "users"=>["Dennis te Beest", "Erwin de Bruin", "Sandra Imholz", "Jacco Wallinga", "Peter Teunis", "Marion Koopmans", "Michiel van Boven"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0113021.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Classification_of_sera_in_the_uni_and_bivariate_mixture_analyses_as_a_function_of_the_microarray_response_to_A_2009_H1N1_/1246051", "title"=>"Classification of sera in the uni- and bivariate mixture analyses as a function of the microarray response to A/2009 (H1N1).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-18 05:07:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/1799689"], "description"=>"<p>Maximum sensitivity plus specificity are 66% and 51% for HI (at a cut-off for standardised HI of 44), 91% and 84% for the univariate microarray (at a microarray titer of 97), and 96% and 95% for the bivariate microarray (at a A/1918 to A/2009 ratio of 0·95).</p>", "links"=>[], "tags"=>["classification", "sensitivity", "hi", "sample sizes", "ha", "data", "1N", "infection attack rates", "ratio", "Mixture Models", "Antibody Protein Microarray Analysis Reliable discrimination", "sera", "hemagglutination inhibition", "antibody responses", "influenza infection", "protein microarray", "virus neutralization tests"], "article_id"=>1246052, "categories"=>["Biological Sciences"], "users"=>["Dennis te Beest", "Erwin de Bruin", "Sandra Imholz", "Jacco Wallinga", "Peter Teunis", "Marion Koopmans", "Michiel van Boven"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0113021.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Receiver_operating_characteristic_ROC_diagram_of_the_univariate_model_based_on_HI_measurements_the_univariate_microarray_data_A_2009_and_the_bivariate_model_of_microarray_data_A_1918_and_A_2009_/1246052", "title"=>"Receiver operating characteristic (ROC) diagram of the univariate model based on HI measurements, the univariate microarray data (A/2009), and the bivariate model of microarray data (A/1918 and A/2009).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-18 05:07:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/1799690"], "description"=>"<p>Antigens in bold have been used for classification of persons as being susceptible to, immune against, or recently infected with pandemic virus (A/2009 H1N1).</p><p>Overview of HA1 antigens included in the protein microarray.</p>", "links"=>[], "tags"=>["classification", "sensitivity", "hi", "sample sizes", "ha", "data", "1N", "infection attack rates", "ratio", "Mixture Models", "Antibody Protein Microarray Analysis Reliable discrimination", "sera", "hemagglutination inhibition", "antibody responses", "influenza infection", "protein microarray", "virus neutralization tests"], "article_id"=>1246053, "categories"=>["Biological Sciences"], "users"=>["Dennis te Beest", "Erwin de Bruin", "Sandra Imholz", "Jacco Wallinga", "Peter Teunis", "Marion Koopmans", "Michiel van Boven"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0113021.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Overview_of_HA1_antigens_included_in_the_protein_microarray_/1246053", "title"=>"Overview of HA1 antigens included in the protein microarray.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-11-18 05:07:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/1799691"], "description"=>"<p>For each group the seroprevalence, i.e. the fraction with a titer higher than the cut-off, is shown. Also shown are the seroprevalence differences between the post-and pre-pandemic samples.</p><p>Overview of the microarray data, stratified by age, cut-off for seropositivity, and study period (pre- versus post-pandemic).</p>", "links"=>[], "tags"=>["classification", "sensitivity", "hi", "sample sizes", "ha", "data", "1N", "infection attack rates", "ratio", "Mixture Models", "Antibody Protein Microarray Analysis Reliable discrimination", "sera", "hemagglutination inhibition", "antibody responses", "influenza infection", "protein microarray", "virus neutralization tests"], "article_id"=>1246054, "categories"=>["Biological Sciences"], "users"=>["Dennis te Beest", "Erwin de Bruin", "Sandra Imholz", "Jacco Wallinga", "Peter Teunis", "Marion Koopmans", "Michiel van Boven"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0113021.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Overview_of_the_microarray_data_stratified_by_age_cut_off_for_seropositivity_and_study_period_pre_versus_post_pandemic_/1246054", "title"=>"Overview of the microarray data, stratified by age, cut-off for seropositivity, and study period (pre- versus post-pandemic).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-11-18 05:07:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/1799692"], "description"=>"<p>Three scenarios are considered, viz. a univariate model that uses A/2009 (H1N1) microarray data (‘Univariate microarray’), a bivariate model that uses A/2009 (H1N1) and A/1918 (H1N1) microarray data (‘Bivariate microarray’), and a univariate model of hemagglutination inhibition data using A/2009 (H1N1) (‘Univariate HI’). See <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0113021#pone.0113021.s002\" target=\"_blank\">Table S2</a> and <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0113021#pone.0113021.s003\" target=\"_blank\">Table S3</a> for estimates of the parameters of the distributions.</p>a)<p>one-sided confidence interval.</p><p>Age-specific estimated probabilities (weights) of the component distributions.</p>", "links"=>[], "tags"=>["classification", "sensitivity", "hi", "sample sizes", "ha", "data", "1N", "infection attack rates", "ratio", "Mixture Models", "Antibody Protein Microarray Analysis Reliable discrimination", "sera", "hemagglutination inhibition", "antibody responses", "influenza infection", "protein microarray", "virus neutralization tests"], "article_id"=>1246055, "categories"=>["Biological Sciences"], "users"=>["Dennis te Beest", "Erwin de Bruin", "Sandra Imholz", "Jacco Wallinga", "Peter Teunis", "Marion Koopmans", "Michiel van Boven"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0113021.t003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Age_specific_estimated_probabilities_weights_of_the_component_distributions_/1246055", "title"=>"Age-specific estimated probabilities (weights) of the component distributions.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-11-18 05:07:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/1799693", "https://ndownloader.figshare.com/files/1799694", "https://ndownloader.figshare.com/files/1799695"], "description"=>"<div><p>Reliable discrimination of recent influenza A infection from previous exposure using hemagglutination inhibition (HI) or virus neutralization tests is currently not feasible. This is due to low sensitivity of the tests and the interference of antibody responses generated by previous infections. Here we investigate the diagnostic characteristics of a newly developed antibody (HA1) protein microarray using data from cross-sectional serological studies carried out before and after the pandemic of 2009. The data are analysed by mixture models, providing a probabilistic classification of sera (susceptible, prior-exposed, recently infected). Estimated sensitivity and specificity for identifying A/2009 infections are low using HI (66% and 51%), and high when using A/2009 microarray data alone or together with A/1918 microarray data (96% and 95%). As a heuristic, a high A/2009 to A/1918 antibody ratio (>1.05) is indicative of recent infection, while a low ratio is indicative of a pre-existing response, even if the A/2009 titer is high. We conclude that highly sensitive and specific classification of individual sera is possible using the protein microarray, thereby enabling precise estimation of age-specific infection attack rates in the population even if sample sizes are small.</p></div>", "links"=>[], "tags"=>["classification", "sensitivity", "hi", "sample sizes", "ha", "data", "1N", "infection attack rates", "ratio", "Mixture Models", "Antibody Protein Microarray Analysis Reliable discrimination", "sera", "hemagglutination inhibition", "antibody responses", "influenza infection", "protein microarray", "virus neutralization tests"], "article_id"=>1246056, "categories"=>["Biological Sciences"], "users"=>["Dennis te Beest", "Erwin de Bruin", "Sandra Imholz", "Jacco Wallinga", "Peter Teunis", "Marion Koopmans", "Michiel van Boven"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0113021.s001", "https://dx.doi.org/10.1371/journal.pone.0113021.s002", "https://dx.doi.org/10.1371/journal.pone.0113021.s003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Discrimination_of_Influenza_Infection_A_2009_H1N1_from_Prior_Exposure_by_Antibody_Protein_Microarray_Analysis_/1246056", "title"=>"Discrimination of Influenza Infection (A/2009 H1N1) from Prior Exposure by Antibody Protein Microarray Analysis", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-11-18 05:07:48"}

PMC Usage Stats | Further Information

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Relative Metric

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