Transformed Recombinant Enrichment Profiling Rapidly Identifies HMW1 as an Intracellular Invasion Locus in Haemophilus influenzae
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{"title"=>"Transformed Recombinant Enrichment Profiling Rapidly Identifies HMW1 as an Intracellular Invasion Locus in Haemophilus influenza", "type"=>"journal", "authors"=>[{"first_name"=>"Joshua Chang", "last_name"=>"Mell", "scopus_author_id"=>"6508248167"}, {"first_name"=>"Cristina", "last_name"=>"Viadas", "scopus_author_id"=>"28667448500"}, {"first_name"=>"Javier", "last_name"=>"Moleres", "scopus_author_id"=>"55348738100"}, {"first_name"=>"Sunita", "last_name"=>"Sinha", "scopus_author_id"=>"7403739105"}, {"first_name"=>"Ariadna", "last_name"=>"Fernández-Calvet", "scopus_author_id"=>"57189035283"}, {"first_name"=>"Eric A.", "last_name"=>"Porsch", "scopus_author_id"=>"18133972700"}, {"first_name"=>"Joseph W.", "last_name"=>"St. Geme", "scopus_author_id"=>"56686688800"}, {"first_name"=>"Corey", "last_name"=>"Nislow", "scopus_author_id"=>"6603107893"}, {"first_name"=>"Rosemary J.", "last_name"=>"Redfield", "scopus_author_id"=>"7006647017"}, {"first_name"=>"Junkal", "last_name"=>"Garmendia", "scopus_author_id"=>"7004009449"}], "year"=>2016, "source"=>"PLoS Pathogens", "identifiers"=>{"pmid"=>"27124727", "doi"=>"10.1371/journal.ppat.1005576", "pui"=>"610216797", "issn"=>"15537374", "sgr"=>"84964845763", "scopus"=>"2-s2.0-84964845763"}, "id"=>"96c9ffb3-b40e-31e0-8695-165d90148ed6", "abstract"=>"Many bacterial species actively take up and recombine homologous DNA into their genomes, called natural competence, a trait that offers a means to identify the genetic basis of naturally occurring phenotypic variation. Here, we describe \"transformed recombinant enrichment profiling\" (TREP), in which natural transformation is used to generate complex pools of recombinants, phenotypic selection is used to enrich for specific recombinants, and deep sequencing is used to survey for the genetic variation responsible. We applied TREP to investigate the genetic architecture of intracellular invasion by the human pathogen Haemophilus influenzae, a trait implicated in persistence during chronic infection. TREP identified the HMW1 adhesin as a crucial factor. Natural transformation of the hmw1 operon from a clinical isolate (86-028NP) into a laboratory isolate that lacks it (Rd KW20) resulted in ~1,000-fold increased invasion into airway epithelial cells. When a distinct recipient (Hi375, already possessing hmw1 and its paralog hmw2) was transformed by the same donor, allelic replacement of hmw2AHi375 by hmw1A86-028NP resulted in a ~100-fold increased intracellular invasion rate. The specific role of hmw1A86-028NP was confirmed by mutant and western blot analyses. Bacterial self-aggregation and adherence to airway cells were also increased in recombinants, suggesting that the high invasiveness induced by hmw1A86-028NP might be a consequence of these phenotypes. However, immunofluorescence results found that intracellular hmw1A86-028NP bacteria likely invaded as groups, instead of as individual bacterial cells, indicating an emergent invasion-specific consequence of hmw1A-mediated self-aggregation.", "link"=>"http://www.mendeley.com/research/transformed-recombinant-enrichment-profiling-rapidly-identifies-hmw1-intracellular-invasion-locus-ha", "reader_count"=>11, "reader_count_by_academic_status"=>{"Librarian"=>2, "Researcher"=>2, "Student > Ph. D. Student"=>1, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>1, "Unspecified"=>1}, "reader_count_by_user_role"=>{"Librarian"=>2, "Researcher"=>2, "Student > Ph. D. Student"=>1, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>1, "Unspecified"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>5, "Arts and Humanities"=>1, "Social Sciences"=>2, "Unspecified"=>1}, "reader_count_by_subdiscipline"=>{"Social Sciences"=>{"Social Sciences"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>1}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"Belgium"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/5030770"], "description"=>"<p>Bacteria self-aggregate and adhere to the epithelial cell surface in clumps, and HMW1-mediated attachments are maintained during uptake by cells into subcellular compartments with endosomal features.</p>", "links"=>[], "tags"=>["Natural transformation", "Intracellular Invasion Locus", "airway cells", "hmw 2A", "intracellular invasion rate", "TREP", "paralog hmw 2", "pathogen Haemophilus influenzae", "HMW 1 adhesin", "blot analyses", "Transformed Recombinant Enrichment Profiling Rapidly Identifies HMW 1", "Haemophilus influenza", "allelic replacement", "NP", "DNA", "intracellular invasion", "KW", "airway epithelial cells", "hmw 1A", "phenotypic variation", "immunofluorescence results", "hmw 1", "hmw 1 operon", "phenotypic selection"], "article_id"=>3205378, "categories"=>["Medicine", "Microbiology", "Cell Biology", "Genetics", "Evolutionary Biology", "Biological Sciences not elsewhere classified", "Cancer", "Infectious Diseases"], "users"=>["Joshua Chang Mell", "Cristina Viadas", "Javier Moleres", "Sunita Sinha", "Ariadna Fernández-Calvet", "Eric A. Porsch", "Joseph W. St. Geme III", "Corey Nislow", "Rosemary J. Redfield", "Junkal Garmendia"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005576.g012", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Model_of_enhanced_intracellular_invasion_by_HMW1_sub_86-028NP_sub_/3205378", "title"=>"Model of enhanced intracellular invasion by HMW1<sub>86-028NP</sub>.", "pos_in_sequence"=>13, "defined_type"=>1, "published_date"=>"2016-04-28 04:55:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/5030710"], "description"=>"<p>For A and B, blue boxes indicate 86-028NP annotations; red is for Rd annotations, and green is for Hi375 annotations. Darker coloring indicates that sense is on the top strand, whereas lighter indicates bottom strand. Genes with names are indicated. The thick black horizontal lines indicate the minimum interval at or near fixation in both the Nov<sup>R</sup> and Nal<sup>R</sup> recombinant pools. <b>(A)</b> RdS recipient. Triangle indicates site of the <i>hmw1</i> insertion. <b>(B)</b> HiT recipient.</p>", "links"=>[], "tags"=>["Natural transformation", "Intracellular Invasion Locus", "airway cells", "hmw 2A", "intracellular invasion rate", "TREP", "paralog hmw 2", "pathogen Haemophilus influenzae", "HMW 1 adhesin", "blot analyses", "Transformed Recombinant Enrichment Profiling Rapidly Identifies HMW 1", "Haemophilus influenza", "allelic replacement", "NP", "DNA", "intracellular invasion", "KW", "airway epithelial cells", "hmw 1A", "phenotypic variation", "immunofluorescence results", "hmw 1", "hmw 1 operon", "phenotypic selection"], "article_id"=>3205348, "categories"=>["Medicine", "Microbiology", "Cell Biology", "Genetics", "Evolutionary Biology", "Biological Sciences not elsewhere classified", "Cancer", "Infectious Diseases"], "users"=>["Joshua Chang Mell", "Cristina Viadas", "Javier Moleres", "Sunita Sinha", "Ariadna Fernández-Calvet", "Eric A. Porsch", "Joseph W. St. Geme III", "Corey Nislow", "Rosemary J. Redfield", "Junkal Garmendia"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005576.g006", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Genomic_map_at_the_enriched_invasion_locus_for_the_three_parental_strains_/3205348", "title"=>"Genomic map at the enriched invasion locus for the three parental strains.", "pos_in_sequence"=>7, "defined_type"=>1, "published_date"=>"2016-04-28 04:55:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/5030740"], "description"=>"<p>Sequencing grouped 16 clones into six genotypes, two RdS Nal<sup>R</sup> (A and B), one RdS Nov<sup>R</sup> (C), one HiT Nal<sup>R</sup> (D) and two HiT Nov<sup>R</sup> (E and F). Genome-wide donor allele frequencies of each clone are shown in <b>(A)</b>. The x-axis indicates the recipient genome coordinate and the y-axis shows donor allele frequency from 0 to 1. Blue arrows mark the antibiotic resistance sites; red arrows mark the invasion locus; and the green arrow marks the <i>hmw2</i> artifact. Clone assignments are in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005576#ppat.1005576.s020\" target=\"_blank\">S8 Table</a> and exact donor segment breakpoints are in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005576#ppat.1005576.s021\" target=\"_blank\">S9 Table</a>. All clones were phenotyped in triplicate and were aggregated by genotype for plots depicting their invasion <b>(B)</b> and adhesion <b>(C)</b> phenotypes. Different symbols within each genotype indicate the specific isolated colony tested (labeled 1–4, as in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005576#ppat.1005576.s020\" target=\"_blank\">S8 Table</a>).</p>", "links"=>[], "tags"=>["Natural transformation", "Intracellular Invasion Locus", "airway cells", "hmw 2A", "intracellular invasion rate", "TREP", "paralog hmw 2", "pathogen Haemophilus influenzae", "HMW 1 adhesin", "blot analyses", "Transformed Recombinant Enrichment Profiling Rapidly Identifies HMW 1", "Haemophilus influenza", "allelic replacement", "NP", "DNA", "intracellular invasion", "KW", "airway epithelial cells", "hmw 1A", "phenotypic variation", "immunofluorescence results", "hmw 1", "hmw 1 operon", "phenotypic selection"], "article_id"=>3205351, "categories"=>["Medicine", "Microbiology", "Cell Biology", "Genetics", "Evolutionary Biology", "Biological Sciences not elsewhere classified", "Cancer", "Infectious Diseases"], "users"=>["Joshua Chang Mell", "Cristina Viadas", "Javier Moleres", "Sunita Sinha", "Ariadna Fernández-Calvet", "Eric A. Porsch", "Joseph W. St. Geme III", "Corey Nislow", "Rosemary J. Redfield", "Junkal Garmendia"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005576.g007", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Genotype_and_phenotype_of_recombinant_clones_from_Pool_4_/3205351", "title"=>"Genotype and phenotype of recombinant clones from Pool 4.", "pos_in_sequence"=>8, "defined_type"=>1, "published_date"=>"2016-04-28 04:55:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/5030776"], "description"=>"<p>HMW adhesin paralog assignment.</p>", "links"=>[], "tags"=>["Natural transformation", "Intracellular Invasion Locus", "airway cells", "hmw 2A", "intracellular invasion rate", "TREP", "paralog hmw 2", "pathogen Haemophilus influenzae", "HMW 1 adhesin", "blot analyses", "Transformed Recombinant Enrichment Profiling Rapidly Identifies HMW 1", "Haemophilus influenza", "allelic replacement", "NP", "DNA", "intracellular invasion", "KW", "airway epithelial cells", "hmw 1A", "phenotypic variation", "immunofluorescence results", "hmw 1", "hmw 1 operon", "phenotypic selection"], "article_id"=>3205384, "categories"=>["Medicine", "Microbiology", "Cell Biology", "Genetics", "Evolutionary Biology", "Biological Sciences not elsewhere classified", "Cancer", "Infectious Diseases"], "users"=>["Joshua Chang Mell", "Cristina Viadas", "Javier Moleres", "Sunita Sinha", "Ariadna Fernández-Calvet", "Eric A. Porsch", "Joseph W. St. Geme III", "Corey Nislow", "Rosemary J. Redfield", "Junkal Garmendia"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005576.t001", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/HMW_adhesin_paralog_assignment_/3205384", "title"=>"HMW adhesin paralog assignment.", "pos_in_sequence"=>14, "defined_type"=>3, "published_date"=>"2016-04-28 04:55:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/5030749"], "description"=>"<p><b>(A)</b> Western blot detection of HMW adhesins with a guinea pig anti-HMW1A gp85 antibody. The 154 kDa protein corresponds to HMW1A<sub>86-028NP</sub>; the 168 kDa protein corresponds to HMW1A<sub>Hi375</sub>, and the 150 kDa protein corresponds to HMW2A<sub>Hi375</sub>. Expression of HMW2A<sub>86-028NP</sub> was not detectable with the antibody used. <b>(B)</b> Intracellular invasion and <b>(C)</b> adhesion by NpNN and HiT derivatives including mutant, recombinant and recombinant mutant strains. Blue indicates NpNN, green indicates the HiT recipient and mutant derivatives, and purple indicates the rHiT recombinant and mutant derivatives. Experiments were run in triplicate on three separate days, as indicated by the three distinct symbols.</p>", "links"=>[], "tags"=>["Natural transformation", "Intracellular Invasion Locus", "airway cells", "hmw 2A", "intracellular invasion rate", "TREP", "paralog hmw 2", "pathogen Haemophilus influenzae", "HMW 1 adhesin", "blot analyses", "Transformed Recombinant Enrichment Profiling Rapidly Identifies HMW 1", "Haemophilus influenza", "allelic replacement", "NP", "DNA", "intracellular invasion", "KW", "airway epithelial cells", "hmw 1A", "phenotypic variation", "immunofluorescence results", "hmw 1", "hmw 1 operon", "phenotypic selection"], "article_id"=>3205357, "categories"=>["Medicine", "Microbiology", "Cell Biology", "Genetics", "Evolutionary Biology", "Biological Sciences not elsewhere classified", "Cancer", "Infectious Diseases"], "users"=>["Joshua Chang Mell", "Cristina Viadas", "Javier Moleres", "Sunita Sinha", "Ariadna Fernández-Calvet", "Eric A. Porsch", "Joseph W. St. Geme III", "Corey Nislow", "Rosemary J. Redfield", "Junkal Garmendia"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005576.g008", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_i_hmw1A_i_sub_i_86-028NP_i_sub_gene_confers_increased_adhesion_and_intracellular_invasion_/3205357", "title"=>"The <i>hmw1A</i><sub><i>86-028NP</i></sub> gene confers increased adhesion and intracellular invasion.", "pos_in_sequence"=>9, "defined_type"=>1, "published_date"=>"2016-04-28 04:55:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/5030782"], "description"=>"<p>Intracellular bacteria immunofluorescence microscopy.</p>", "links"=>[], "tags"=>["Natural transformation", "Intracellular Invasion Locus", "airway cells", "hmw 2A", "intracellular invasion rate", "TREP", "paralog hmw 2", "pathogen Haemophilus influenzae", "HMW 1 adhesin", "blot analyses", "Transformed Recombinant Enrichment Profiling Rapidly Identifies HMW 1", "Haemophilus influenza", "allelic replacement", "NP", "DNA", "intracellular invasion", "KW", "airway epithelial cells", "hmw 1A", "phenotypic variation", "immunofluorescence results", "hmw 1", "hmw 1 operon", "phenotypic selection"], "article_id"=>3205390, "categories"=>["Medicine", "Microbiology", "Cell Biology", "Genetics", "Evolutionary Biology", "Biological Sciences not elsewhere classified", "Cancer", "Infectious Diseases"], "users"=>["Joshua Chang Mell", "Cristina Viadas", "Javier Moleres", "Sunita Sinha", "Ariadna Fernández-Calvet", "Eric A. Porsch", "Joseph W. St. Geme III", "Corey Nislow", "Rosemary J. Redfield", "Junkal Garmendia"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005576.t002", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Intracellular_bacteria_immunofluorescence_microscopy_/3205390", "title"=>"Intracellular bacteria immunofluorescence microscopy.", "pos_in_sequence"=>15, "defined_type"=>3, "published_date"=>"2016-04-28 04:55:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/5030608", "https://ndownloader.figshare.com/files/5030644", "https://ndownloader.figshare.com/files/5030647", "https://ndownloader.figshare.com/files/5030650", "https://ndownloader.figshare.com/files/5030653", "https://ndownloader.figshare.com/files/5030656", "https://ndownloader.figshare.com/files/5030659", "https://ndownloader.figshare.com/files/5030662", "https://ndownloader.figshare.com/files/5030665", "https://ndownloader.figshare.com/files/5030671", "https://ndownloader.figshare.com/files/5030641", "https://ndownloader.figshare.com/files/5030638", "https://ndownloader.figshare.com/files/5030611", "https://ndownloader.figshare.com/files/5030614", "https://ndownloader.figshare.com/files/5030617", "https://ndownloader.figshare.com/files/5030620", "https://ndownloader.figshare.com/files/5030623", "https://ndownloader.figshare.com/files/5030626", "https://ndownloader.figshare.com/files/5030629", "https://ndownloader.figshare.com/files/5030632", "https://ndownloader.figshare.com/files/5030635", "https://ndownloader.figshare.com/files/5030677"], "description"=>"<div><p>Many bacterial species actively take up and recombine homologous DNA into their genomes, called natural competence, a trait that offers a means to identify the genetic basis of naturally occurring phenotypic variation. Here, we describe “transformed recombinant enrichment profiling” (TREP), in which natural transformation is used to generate complex pools of recombinants, phenotypic selection is used to enrich for specific recombinants, and deep sequencing is used to survey for the genetic variation responsible. We applied TREP to investigate the genetic architecture of intracellular invasion by the human pathogen <i>Haemophilus influenzae</i>, a trait implicated in persistence during chronic infection. TREP identified the HMW1 adhesin as a crucial factor. Natural transformation of the <i>hmw1</i> operon from a clinical isolate (86-028NP) into a laboratory isolate that lacks it (Rd KW20) resulted in ~1,000-fold increased invasion into airway epithelial cells. When a distinct recipient (Hi375, already possessing <i>hmw1</i> and its paralog <i>hmw2</i>) was transformed by the same donor, allelic replacement of <i>hmw2A</i><sub><i>Hi375</i></sub> by <i>hmw1A</i><sub><i>86-028NP</i></sub> resulted in a ~100-fold increased intracellular invasion rate. The specific role of <i>hmw1A</i><sub><i>86-028NP</i></sub> was confirmed by mutant and western blot analyses. Bacterial self-aggregation and adherence to airway cells were also increased in recombinants, suggesting that the high invasiveness induced by <i>hmw1A</i><sub><i>86-028NP</i></sub> might be a consequence of these phenotypes. However, immunofluorescence results found that intracellular <i>hmw1A</i><sub><i>86-028NP</i></sub> bacteria likely invaded as groups, instead of as individual bacterial cells, indicating an emergent invasion-specific consequence of <i>hmw1A</i>-mediated self-aggregation.</p></div>", "links"=>[], "tags"=>["Natural transformation", "Intracellular Invasion Locus", "airway cells", "hmw 2A", "intracellular invasion rate", "TREP", "paralog hmw 2", "pathogen Haemophilus influenzae", "HMW 1 adhesin", "blot analyses", "Transformed Recombinant Enrichment Profiling Rapidly Identifies HMW 1", "Haemophilus influenza", "allelic replacement", "NP", "DNA", "intracellular invasion", "KW", "airway epithelial cells", "hmw 1A", "phenotypic variation", "immunofluorescence results", "hmw 1", "hmw 1 operon", "phenotypic selection"], "article_id"=>3205327, "categories"=>["Medicine", "Microbiology", "Cell Biology", "Genetics", "Evolutionary Biology", "Biological Sciences not elsewhere classified", "Cancer", "Infectious Diseases"], "users"=>["Joshua Chang Mell", "Cristina Viadas", "Javier Moleres", "Sunita Sinha", "Ariadna Fernández-Calvet", "Eric A. Porsch", "Joseph W. St. Geme III", "Corey Nislow", "Rosemary J. Redfield", "Junkal Garmendia"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1005576.s001", "https://dx.doi.org/10.1371/journal.ppat.1005576.s013", "https://dx.doi.org/10.1371/journal.ppat.1005576.s014", "https://dx.doi.org/10.1371/journal.ppat.1005576.s015", "https://dx.doi.org/10.1371/journal.ppat.1005576.s016", "https://dx.doi.org/10.1371/journal.ppat.1005576.s017", "https://dx.doi.org/10.1371/journal.ppat.1005576.s018", "https://dx.doi.org/10.1371/journal.ppat.1005576.s019", "https://dx.doi.org/10.1371/journal.ppat.1005576.s020", "https://dx.doi.org/10.1371/journal.ppat.1005576.s021", "https://dx.doi.org/10.1371/journal.ppat.1005576.s012", "https://dx.doi.org/10.1371/journal.ppat.1005576.s011", "https://dx.doi.org/10.1371/journal.ppat.1005576.s002", "https://dx.doi.org/10.1371/journal.ppat.1005576.s003", "https://dx.doi.org/10.1371/journal.ppat.1005576.s004", "https://dx.doi.org/10.1371/journal.ppat.1005576.s005", "https://dx.doi.org/10.1371/journal.ppat.1005576.s006", "https://dx.doi.org/10.1371/journal.ppat.1005576.s007", "https://dx.doi.org/10.1371/journal.ppat.1005576.s008", "https://dx.doi.org/10.1371/journal.ppat.1005576.s009", "https://dx.doi.org/10.1371/journal.ppat.1005576.s010", "https://dx.doi.org/10.1371/journal.ppat.1005576.s022"], "stats"=>{"downloads"=>22, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Transformed_Recombinant_Enrichment_Profiling_Rapidly_Identifies_HMW1_as_an_Intracellular_Invasion_Locus_in_i_Haemophilus_influenza_i_/3205327", "title"=>"Transformed Recombinant Enrichment Profiling Rapidly Identifies HMW1 as an Intracellular Invasion Locus in <i>Haemophilus influenza</i>", "pos_in_sequence"=>1, "defined_type"=>4, "published_date"=>"2016-04-28 04:55:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/5030680"], "description"=>"<p><b>(A)</b> Genomic DNA from a strain with high invasiveness is transformed into naturally competent cells of a strain with poor invasiveness. This produces complex pools of recombinants, in which short stretches of donor DNA replace homologous recipient DNA in individual recombinants. <b>(B)</b> Rare recombinants with increased invasiveness are enriched by serial passage of recombinant pools through A549 alveolar epithelial cells using gentamicin protection assays. Finally <b>(C)</b>, the selected locus/loci are identified from donor allele frequencies measured by deep sequencing.</p>", "links"=>[], "tags"=>["Natural transformation", "Intracellular Invasion Locus", "airway cells", "hmw 2A", "intracellular invasion rate", "TREP", "paralog hmw 2", "pathogen Haemophilus influenzae", "HMW 1 adhesin", "blot analyses", "Transformed Recombinant Enrichment Profiling Rapidly Identifies HMW 1", "Haemophilus influenza", "allelic replacement", "NP", "DNA", "intracellular invasion", "KW", "airway epithelial cells", "hmw 1A", "phenotypic variation", "immunofluorescence results", "hmw 1", "hmw 1 operon", "phenotypic selection"], "article_id"=>3205330, "categories"=>["Medicine", "Microbiology", "Cell Biology", "Genetics", "Evolutionary Biology", "Biological Sciences not elsewhere classified", "Cancer", "Infectious Diseases"], "users"=>["Joshua Chang Mell", "Cristina Viadas", "Javier Moleres", "Sunita Sinha", "Ariadna Fernández-Calvet", "Eric A. Porsch", "Joseph W. St. Geme III", "Corey Nislow", "Rosemary J. Redfield", "Junkal Garmendia"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005576.g001", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Schematic_of_transformed_recombinant_enrichment_profiling_TREP_to_map_i_H_i_i_influenzae_i_intracellular_invasion_genes_/3205330", "title"=>"Schematic of transformed recombinant enrichment profiling (TREP) to map <i>H</i>. <i>influenzae</i> intracellular invasion genes.", "pos_in_sequence"=>2, "defined_type"=>1, "published_date"=>"2016-04-28 04:55:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/5030755"], "description"=>"<p>Bacteria scraped from chocolate agar plates were suspended into 35 ml of sBHI normalized to OD<sub>600</sub> = 0.5 in a 50 ml conical tube and allowed to sit on the lab bench. The OD<sub>600</sub> at the top of the cultures was followed over time as a proxy for clumping/self-aggregation. Error bars indicate the standard deviation from four replicate assays run on different days.</p>", "links"=>[], "tags"=>["Natural transformation", "Intracellular Invasion Locus", "airway cells", "hmw 2A", "intracellular invasion rate", "TREP", "paralog hmw 2", "pathogen Haemophilus influenzae", "HMW 1 adhesin", "blot analyses", "Transformed Recombinant Enrichment Profiling Rapidly Identifies HMW 1", "Haemophilus influenza", "allelic replacement", "NP", "DNA", "intracellular invasion", "KW", "airway epithelial cells", "hmw 1A", "phenotypic variation", "immunofluorescence results", "hmw 1", "hmw 1 operon", "phenotypic selection"], "article_id"=>3205363, "categories"=>["Medicine", "Microbiology", "Cell Biology", "Genetics", "Evolutionary Biology", "Biological Sciences not elsewhere classified", "Cancer", "Infectious Diseases"], "users"=>["Joshua Chang Mell", "Cristina Viadas", "Javier Moleres", "Sunita Sinha", "Ariadna Fernández-Calvet", "Eric A. Porsch", "Joseph W. St. Geme III", "Corey Nislow", "Rosemary J. Redfield", "Junkal Garmendia"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005576.g009", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Self-aggregation_is_increased_by_i_hmw1A_i_sub_i_86-028NP_i_sub_/3205363", "title"=>"Self-aggregation is increased by <i>hmw1A</i><sub><i>86-028NP</i></sub>.", "pos_in_sequence"=>10, "defined_type"=>1, "published_date"=>"2016-04-28 04:55:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/5030683"], "description"=>"<p><b>(A)</b> “Invaders/CFU” was calculated as the total gentamicin-protected CFU / total input CFU. <b>(B)</b> “Adherents/CFU” was calculated as above with gentamicin treatment excluded. Triplicate experiments were conducted three times for RdS and HiT recipients and five times for the NpNN donor. Boxplots outline the first and third quartiles, with the thick horizontal line indicating the median, and the whiskers extend 1.5 times the interquartile distance.</p>", "links"=>[], "tags"=>["Natural transformation", "Intracellular Invasion Locus", "airway cells", "hmw 2A", "intracellular invasion rate", "TREP", "paralog hmw 2", "pathogen Haemophilus influenzae", "HMW 1 adhesin", "blot analyses", "Transformed Recombinant Enrichment Profiling Rapidly Identifies HMW 1", "Haemophilus influenza", "allelic replacement", "NP", "DNA", "intracellular invasion", "KW", "airway epithelial cells", "hmw 1A", "phenotypic variation", "immunofluorescence results", "hmw 1", "hmw 1 operon", "phenotypic selection"], "article_id"=>3205333, "categories"=>["Medicine", "Microbiology", "Cell Biology", "Genetics", "Evolutionary Biology", "Biological Sciences not elsewhere classified", "Cancer", "Infectious Diseases"], "users"=>["Joshua Chang Mell", "Cristina Viadas", "Javier Moleres", "Sunita Sinha", "Ariadna Fernández-Calvet", "Eric A. Porsch", "Joseph W. St. Geme III", "Corey Nislow", "Rosemary J. Redfield", "Junkal Garmendia"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005576.g002", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Invasion_and_adhesion_in_the_parent_strains_/3205333", "title"=>"Invasion and adhesion in the parent strains.", "pos_in_sequence"=>3, "defined_type"=>1, "published_date"=>"2016-04-28 04:55:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/5030686"], "description"=>"<p><b>(A)</b> Boxplots of intracellular invasion frequencies from Pools 0–4 (2 experiments in triplicate). <b>(B)</b> Boxplots of adhesion frequencies (2 experiments in triplicate). The values show the combined ability of clones in Pool <i>n</i> to invade or adhere to airway epithelial cells, while the recovered colonies comprise Pool <i>n+</i>1. Nal<sup>R</sup> and Nov<sup>R</sup> pools are summarized by the left and right boxplots, with individual data points shown as circles and squares, respectively.</p>", "links"=>[], "tags"=>["Natural transformation", "Intracellular Invasion Locus", "airway cells", "hmw 2A", "intracellular invasion rate", "TREP", "paralog hmw 2", "pathogen Haemophilus influenzae", "HMW 1 adhesin", "blot analyses", "Transformed Recombinant Enrichment Profiling Rapidly Identifies HMW 1", "Haemophilus influenza", "allelic replacement", "NP", "DNA", "intracellular invasion", "KW", "airway epithelial cells", "hmw 1A", "phenotypic variation", "immunofluorescence results", "hmw 1", "hmw 1 operon", "phenotypic selection"], "article_id"=>3205336, "categories"=>["Medicine", "Microbiology", "Cell Biology", "Genetics", "Evolutionary Biology", "Biological Sciences not elsewhere classified", "Cancer", "Infectious Diseases"], "users"=>["Joshua Chang Mell", "Cristina Viadas", "Javier Moleres", "Sunita Sinha", "Ariadna Fernández-Calvet", "Eric A. Porsch", "Joseph W. St. Geme III", "Corey Nislow", "Rosemary J. Redfield", "Junkal Garmendia"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005576.g003", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Serial_enrichment_for_invasive_recombinants_by_gentamicin_protection_/3205336", "title"=>"Serial enrichment for invasive recombinants by gentamicin protection.", "pos_in_sequence"=>4, "defined_type"=>1, "published_date"=>"2016-04-28 04:55:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/5030761"], "description"=>"<p>A549 cells were infected by NpNN, RdS, rRdS, HiT, rHiT, or rHiTΔ<i>hmw1A</i><sub><i>86-028NP</i></sub>. In the merged images, reactivity with an anti-NTHi antibody is shown in green, Lamp-1 stain is shown in red, and DNA stained with Hoechst 33342 is shown in blue. Images were taken at 1 h post-gentamicin treatment. The scale bar in the lower right indicates 5 microns; individual bacterial cells are ~1 micron in diameter.</p>", "links"=>[], "tags"=>["Natural transformation", "Intracellular Invasion Locus", "airway cells", "hmw 2A", "intracellular invasion rate", "TREP", "paralog hmw 2", "pathogen Haemophilus influenzae", "HMW 1 adhesin", "blot analyses", "Transformed Recombinant Enrichment Profiling Rapidly Identifies HMW 1", "Haemophilus influenza", "allelic replacement", "NP", "DNA", "intracellular invasion", "KW", "airway epithelial cells", "hmw 1A", "phenotypic variation", "immunofluorescence results", "hmw 1", "hmw 1 operon", "phenotypic selection"], "article_id"=>3205369, "categories"=>["Medicine", "Microbiology", "Cell Biology", "Genetics", "Evolutionary Biology", "Biological Sciences not elsewhere classified", "Cancer", "Infectious Diseases"], "users"=>["Joshua Chang Mell", "Cristina Viadas", "Javier Moleres", "Sunita Sinha", "Ariadna Fernández-Calvet", "Eric A. Porsch", "Joseph W. St. Geme III", "Corey Nislow", "Rosemary J. Redfield", "Junkal Garmendia"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005576.g010", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Co-localization_of_intracellular_bacteria_and_the_Lamp-1_endosomal_marker_/3205369", "title"=>"Co-localization of intracellular bacteria and the Lamp-1 endosomal marker.", "pos_in_sequence"=>11, "defined_type"=>1, "published_date"=>"2016-04-28 04:55:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/5030689"], "description"=>"<p><b>(A)</b> RdS Nov<sup>R</sup>. <b>(B)</b> RdS Nal<sup>R</sup>. The x-axes indicate recipient genome coordinate, and the y-axes indicate the percent donor alleles. Blue dots and grey lines indicate donor-specific SNPs. Salmon color shows the limits of detection, or 1/depth (alignments with mapping quality = 0 were ignored, which excludes multiply mapping reads). Pools are indicated as P<i>n</i>. The two wide views at the top of <b>A</b> and <b>B</b> show the genome-wide donor allele frequencies for Pool 0 and Pool 8, whereas the lower four zoom around the nearly fixed locus selected for by serial gentamicin protection assay (indicated by purple circles) for Pools 0, 2, 4, and 8.</p>", "links"=>[], "tags"=>["Natural transformation", "Intracellular Invasion Locus", "airway cells", "hmw 2A", "intracellular invasion rate", "TREP", "paralog hmw 2", "pathogen Haemophilus influenzae", "HMW 1 adhesin", "blot analyses", "Transformed Recombinant Enrichment Profiling Rapidly Identifies HMW 1", "Haemophilus influenza", "allelic replacement", "NP", "DNA", "intracellular invasion", "KW", "airway epithelial cells", "hmw 1A", "phenotypic variation", "immunofluorescence results", "hmw 1", "hmw 1 operon", "phenotypic selection"], "article_id"=>3205339, "categories"=>["Medicine", "Microbiology", "Cell Biology", "Genetics", "Evolutionary Biology", "Biological Sciences not elsewhere classified", "Cancer", "Infectious Diseases"], "users"=>["Joshua Chang Mell", "Cristina Viadas", "Javier Moleres", "Sunita Sinha", "Ariadna Fernández-Calvet", "Eric A. Porsch", "Joseph W. St. Geme III", "Corey Nislow", "Rosemary J. Redfield", "Junkal Garmendia"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005576.g004", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Genomic_profile_of_the_RdS_recombinant_pools_/3205339", "title"=>"Genomic profile of the RdS recombinant pools.", "pos_in_sequence"=>5, "defined_type"=>1, "published_date"=>"2016-04-28 04:55:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/5030764"], "description"=>"<p>(<b>A</b>) Invasion and (<b>B</b>) adherence phenotypes of Rd, Rd <i>hmw1</i><sub><i>strain12</i></sub>, and strain 12 were evaluated in A549 cells in triplicate on three separate days (shown by distinct symbols).</p>", "links"=>[], "tags"=>["Natural transformation", "Intracellular Invasion Locus", "airway cells", "hmw 2A", "intracellular invasion rate", "TREP", "paralog hmw 2", "pathogen Haemophilus influenzae", "HMW 1 adhesin", "blot analyses", "Transformed Recombinant Enrichment Profiling Rapidly Identifies HMW 1", "Haemophilus influenza", "allelic replacement", "NP", "DNA", "intracellular invasion", "KW", "airway epithelial cells", "hmw 1A", "phenotypic variation", "immunofluorescence results", "hmw 1", "hmw 1 operon", "phenotypic selection"], "article_id"=>3205372, "categories"=>["Medicine", "Microbiology", "Cell Biology", "Genetics", "Evolutionary Biology", "Biological Sciences not elsewhere classified", "Cancer", "Infectious Diseases"], "users"=>["Joshua Chang Mell", "Cristina Viadas", "Javier Moleres", "Sunita Sinha", "Ariadna Fernández-Calvet", "Eric A. Porsch", "Joseph W. St. Geme III", "Corey Nislow", "Rosemary J. Redfield", "Junkal Garmendia"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005576.g011", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_i_hmw1_i_sub_i_strain12_i_sub_allele_confers_increased_intracellular_invasion_to_Rd_KW20_/3205372", "title"=>"The <i>hmw1</i><sub><i>strain12</i></sub> allele confers increased intracellular invasion to Rd KW20.", "pos_in_sequence"=>12, "defined_type"=>1, "published_date"=>"2016-04-28 04:55:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/5030692"], "description"=>"<p><b>(A)</b> HiT Nov<sup>R</sup>. <b>(B)</b> HiT Nal<sup>R</sup>. Plotting as in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005576#ppat.1005576.g004\" target=\"_blank\">Fig 4</a>, with the green circles indicating a multi-mapping artifact. Low limits of detection (1/depth, salmon color) within the invasion locus are due to alignments with mapping quality = 0 (multiply mapping reads) caused by the same sequencing artifact.</p>", "links"=>[], "tags"=>["Natural transformation", "Intracellular Invasion Locus", "airway cells", "hmw 2A", "intracellular invasion rate", "TREP", "paralog hmw 2", "pathogen Haemophilus influenzae", "HMW 1 adhesin", "blot analyses", "Transformed Recombinant Enrichment Profiling Rapidly Identifies HMW 1", "Haemophilus influenza", "allelic replacement", "NP", "DNA", "intracellular invasion", "KW", "airway epithelial cells", "hmw 1A", "phenotypic variation", "immunofluorescence results", "hmw 1", "hmw 1 operon", "phenotypic selection"], "article_id"=>3205342, "categories"=>["Medicine", "Microbiology", "Cell Biology", "Genetics", "Evolutionary Biology", "Biological Sciences not elsewhere classified", "Cancer", "Infectious Diseases"], "users"=>["Joshua Chang Mell", "Cristina Viadas", "Javier Moleres", "Sunita Sinha", "Ariadna Fernández-Calvet", "Eric A. Porsch", "Joseph W. St. Geme III", "Corey Nislow", "Rosemary J. Redfield", "Junkal Garmendia"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005576.g005", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Genomic_profile_of_the_HiT_recombinant_pools_/3205342", "title"=>"Genomic profile of the HiT recombinant pools.", "pos_in_sequence"=>6, "defined_type"=>1, "published_date"=>"2016-04-28 04:55:24"}

PMC Usage Stats | Further Information

  • {"unique-ip"=>"31", "full-text"=>"22", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"20", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"15", "full-text"=>"15", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"21", "full-text"=>"22", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"16", "full-text"=>"13", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"12", "full-text"=>"13", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"16", "full-text"=>"10", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"9", "full-text"=>"11", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"7", "full-text"=>"5", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"23", "full-text"=>"6", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"15", "cited-by"=>"2", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"8", "full-text"=>"10", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"6", "full-text"=>"7", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"2"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"6", "full-text"=>"7", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"10", "full-text"=>"13", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"11", "full-text"=>"12", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"11", "full-text"=>"4", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"6", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"13", "full-text"=>"11", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"12", "full-text"=>"10", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"5", "full-text"=>"2", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"13", "supp-data"=>"11", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"12", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"8", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"8", "full-text"=>"10", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"14", "full-text"=>"15", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"13", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}

Relative Metric

{"start_date"=>"2016-01-01T00:00:00Z", "end_date"=>"2016-12-31T00:00:00Z", "subject_areas"=>[]}
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