Host Transcriptional Response to Influenza and Other Acute Respiratory Viral Infections – A Prospective Cohort Study
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{"title"=>"Host Transcriptional Response to Influenza and Other Acute Respiratory Viral Infections – A Prospective Cohort Study", "type"=>"journal", "authors"=>[{"first_name"=>"Yijie", "last_name"=>"Zhai", "scopus_author_id"=>"55503543900"}, {"first_name"=>"Luis M.", "last_name"=>"Franco", "scopus_author_id"=>"56745594700"}, {"first_name"=>"Robert L.", "last_name"=>"Atmar", "scopus_author_id"=>"7005296248"}, {"first_name"=>"John M.", "last_name"=>"Quarles", "scopus_author_id"=>"56456235100"}, {"first_name"=>"Nancy", "last_name"=>"Arden", "scopus_author_id"=>"7006658326"}, {"first_name"=>"Kristine L.", "last_name"=>"Bucasas", "scopus_author_id"=>"35486689100"}, {"first_name"=>"Janet M.", "last_name"=>"Wells", "scopus_author_id"=>"7403356908"}, {"first_name"=>"Diane", "last_name"=>"Niño", "scopus_author_id"=>"16936323000"}, {"first_name"=>"Xueqing", "last_name"=>"Wang", "scopus_author_id"=>"11241515400"}, {"first_name"=>"Gladys E.", "last_name"=>"Zapata", "scopus_author_id"=>"15758520300"}, {"first_name"=>"Chad A.", "last_name"=>"Shaw", "scopus_author_id"=>"7402630230"}, {"first_name"=>"John W.", "last_name"=>"Belmont", "scopus_author_id"=>"7006437037"}, {"first_name"=>"Robert B.", "last_name"=>"Couch", "scopus_author_id"=>"7102611225"}], "year"=>2015, "source"=>"PLoS Pathogens", "identifiers"=>{"scopus"=>"2-s2.0-84936802478", "sgr"=>"84936802478", "doi"=>"10.1371/journal.ppat.1004869", "pui"=>"605162019", "pmid"=>"26070066", "isbn"=>"0014-3820", "issn"=>"15537374"}, "id"=>"fdda045a-0fd6-3dea-8c39-dff5330fe496", "abstract"=>"To better understand the systemic response to naturally acquired acute respiratory viral infections, we prospectively enrolled 1610 healthy adults in 2009 and 2010. Of these, 142 subjects were followed for detailed evaluation of acute viral respiratory illness. We examined peripheral blood gene expression at 7 timepoints: enrollment, 5 illness visits and the end of each year of the study. 133 completed all study visits and yielded technically adequate peripheral blood microarray gene expression data. Seventy-three (55%) had an influenza virus infection, 64 influenza A and 9 influenza B. The remaining subjects had a rhinovirus infection (N = 32), other viral infections (N = 4), or no viral agent identified (N = 24). The results, which were replicated between two seasons, showed a dramatic upregulation of interferon pathway and innate immunity genes. This persisted for 2-4 days. The data show a recovery phase at days 4 and 6 with differentially expressed transcripts implicated in cell proliferation and repair. By day 21 the gene expression pattern was indistinguishable from baseline (enrollment). Influenza virus infection induced a higher magnitude and longer duration of the shared expression signature of illness compared to the other viral infections. Using lineage and activation state-specific transcripts to produce cell composition scores, patterns of B and T lymphocyte depressions accompanied by a major activation of NK cells were detected in the acute phase of illness. The data also demonstrate multiple dynamic gene modules that are reorganized and strengthened following infection. Finally, we examined pre- and post-infection anti-influenza antibody titers defining novel gene expression correlates.", "link"=>"http://www.mendeley.com/research/host-transcriptional-response-influenza-other-acute-respiratory-viral-infections-prospective-cohort", "reader_count"=>54, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>4, "Researcher"=>11, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>18, "Student > Postgraduate"=>4, "Student > Master"=>6, "Student > Bachelor"=>3, "Lecturer"=>2, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>4, "Researcher"=>11, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>18, "Student > Postgraduate"=>4, "Student > Master"=>6, "Student > Bachelor"=>3, "Lecturer"=>2, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>8, "Mathematics"=>1, "Agricultural and Biological Sciences"=>20, "Medicine and Dentistry"=>11, "Computer Science"=>2, "Immunology and Microbiology"=>7}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>11}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>7}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>20}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>8}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>4}}, "reader_count_by_country"=>{"Canada"=>1, "Netherlands"=>2, "United States"=>2, "Taiwan"=>1, "United Kingdom"=>1}, "group_count"=>2}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2109321"], "description"=>"<p>Top downregulated genes in the recovery phase of influenza virus infection.</p>", "links"=>[], "tags"=>["expression signature", "64 influenza", "7 timepoints", "immunity genes", "T lymphocyte depressions", "NK cells", "novel gene expression correlates", "Blood Gene Expression", "5 illness visits", "interferon pathway", "influenza virus infection", "Rhinovirus infection", "Cell proliferation", "9 influenza B", "day 21", "days 4", "gene expression pattern", "study visits", "blood microarray gene expression data", "recovery phase", "gene modules", "142 subjects", "Prospective Cohort Study", "cell composition scores", "data show", "host transcriptional response"], "article_id"=>1448065, "categories"=>["Biological Sciences"], "users"=>["Yijie Zhai", "Luis M. Franco", "Robert L. Atmar", "John M. Quarles", "Nancy Arden", "Kristine L. Bucasas", "Janet M. Wells", "Diane Niño", "Xueqing Wang", "Gladys E. Zapata", "Chad A. Shaw", "John W. Belmont", "Robert B. Couch"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004869.t005", "stats"=>{"downloads"=>4, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Top_downregulated_genes_in_the_recovery_phase_of_influenza_virus_infection_/1448065", "title"=>"Top downregulated genes in the recovery phase of influenza virus infection.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-06-12 03:45:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/2109322"], "description"=>"<p>*NA = No significant (Benjamini-adj. <i>P</i> value < 0.05) GO term enrichment were observed.</p><p>GO functional enrichment analysis for the 26 modules detected by WGCNA on different days after influenza virus infection.</p>", "links"=>[], "tags"=>["expression signature", "64 influenza", "7 timepoints", "immunity genes", "T lymphocyte depressions", "NK cells", "novel gene expression correlates", "Blood Gene Expression", "5 illness visits", "interferon pathway", "influenza virus infection", "Rhinovirus infection", "Cell proliferation", "9 influenza B", "day 21", "days 4", "gene expression pattern", "study visits", "blood microarray gene expression data", "recovery phase", "gene modules", "142 subjects", "Prospective Cohort Study", "cell composition scores", "data show", "host transcriptional response"], "article_id"=>1448066, "categories"=>["Biological Sciences"], "users"=>["Yijie Zhai", "Luis M. Franco", "Robert L. Atmar", "John M. Quarles", "Nancy Arden", "Kristine L. Bucasas", "Janet M. Wells", "Diane Niño", "Xueqing Wang", "Gladys E. Zapata", "Chad A. Shaw", "John W. Belmont", "Robert B. Couch"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004869.t006", "stats"=>{"downloads"=>8, "page_views"=>68, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_GO_functional_enrichment_analysis_for_the_26_modules_detected_by_WGCNA_on_different_days_after_influenza_virus_infection_/1448066", "title"=>"GO functional enrichment analysis for the 26 modules detected by WGCNA on different days after influenza virus infection.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-06-12 03:45:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/2109303"], "description"=>"<p>Lineage specific transcripts lists were obtained (<a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004869#ppat.1004869.s011\" target=\"_blank\">S3 Table</a>) and then mapped on to the Illumina array probe identifications. The fold changes of the lineage-specific markers on each day represent the differences to the baseline expression levels on a log<sub>2</sub> scale. Error bars show one standard deviation above and below the average of all the influenza-infected individuals.</p>", "links"=>[], "tags"=>["expression signature", "64 influenza", "7 timepoints", "immunity genes", "T lymphocyte depressions", "NK cells", "novel gene expression correlates", "Blood Gene Expression", "5 illness visits", "interferon pathway", "influenza virus infection", "Rhinovirus infection", "Cell proliferation", "9 influenza B", "day 21", "days 4", "gene expression pattern", "study visits", "blood microarray gene expression data", "recovery phase", "gene modules", "142 subjects", "Prospective Cohort Study", "cell composition scores", "data show", "host transcriptional response"], "article_id"=>1448049, "categories"=>["Biological Sciences"], "users"=>["Yijie Zhai", "Luis M. Franco", "Robert L. Atmar", "John M. Quarles", "Nancy Arden", "Kristine L. Bucasas", "Janet M. Wells", "Diane Niño", "Xueqing Wang", "Gladys E. Zapata", "Chad A. Shaw", "John W. Belmont", "Robert B. Couch"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004869.g003", "stats"=>{"downloads"=>2, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_There_is_little_change_in_the_expression_of_NK_cell_lineage_markers_A_but_a_significant_increase_in_NK_cell_lineage_activation_genes_B_during_the_course_of_influenza_/1448049", "title"=>"There is little change in the expression of NK cell lineage markers (A), but a significant increase in NK cell lineage activation genes (B) during the course of influenza.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-12 03:45:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/2109296"], "description"=>"<p><b>(A)</b> 1610 individuals were enrolled before the influenza season in 2009 and 2010. Peripheral blood samples and nasal secretion samples were collected from each subject at the beginning of enrollment for influenza antibody tests. Genomic DNA and whole blood RNA were obtained from blood samples. Those subjects who became ill with influenza-like symptoms (N = 142) were seen within 48 hours of onset and 2, 4, and 6 days later for repeat evaluation, specimen collections, and medical care and 21 days later for collection of convalescent specimens. Nasal wash samples were collected for virus detection on day 0 and day 2. 1509 of the enrolled subjects completed the study and were called back in the spring of the next year for collecting whole blood RNA, serum and nasal wash samples. <b>(B)</b> Sample size and data generation.</p>", "links"=>[], "tags"=>["expression signature", "64 influenza", "7 timepoints", "immunity genes", "T lymphocyte depressions", "NK cells", "novel gene expression correlates", "Blood Gene Expression", "5 illness visits", "interferon pathway", "influenza virus infection", "Rhinovirus infection", "Cell proliferation", "9 influenza B", "day 21", "days 4", "gene expression pattern", "study visits", "blood microarray gene expression data", "recovery phase", "gene modules", "142 subjects", "Prospective Cohort Study", "cell composition scores", "data show", "host transcriptional response"], "article_id"=>1448042, "categories"=>["Biological Sciences"], "users"=>["Yijie Zhai", "Luis M. Franco", "Robert L. Atmar", "John M. Quarles", "Nancy Arden", "Kristine L. Bucasas", "Janet M. Wells", "Diane Niño", "Xueqing Wang", "Gladys E. Zapata", "Chad A. Shaw", "John W. Belmont", "Robert B. Couch"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004869.g001", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Study_design_and_analysis_scheme_/1448042", "title"=>"Study design and analysis scheme.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-12 03:45:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/2109302"], "description"=>"<p><b>(A-C)</b> Peripheral blood cell composition was altered by influenza virus infection. Cell scores for <b>(A)</b> lymphocyte, <b>(B)</b> neutrophil and <b>(C)</b> monocyte were computed for each sample from influenza-infected individuals, by taking the PC1 of normalized expression levels of the lineage-specific gene sets (See <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004869#ppat.1004869.s011\" target=\"_blank\">S3 Table</a> for the list of lineage specific genes). One-way analysis of variance (ANOVA) was used to determine whether there are significant differences between each illness day and baseline. <b>(D-E)</b> Heatmaps demonstrating the time course of the genes showing the most significant pattern of differential expression compared to baseline in patients with influenza virus and/or rhinovirus infection. <b>(D)</b> 2009 Cohort, <b>(E)</b> 2010 Cohort. Each column corresponds to an individual RNA sample and each row represents the mean-centered, normalized expression values for each of the differentially expressed genes (BH-corrected <i>P</i> values <0.05, |log<sub>2</sub> FC| >1 in both 2009 and 2010 cohorts). Samples were grouped by day and subjects were grouped by infections status (influenza virus infection group includes influenza A, influenza B, influenza A +rhinovirus and influenza B +rhinovirus infections). The transcript order was determined by hierarchical clustering and the order was the same in the two heatmaps. There are three clear phases of transcriptional regulation in response to infection– 1) an acute phase seen on the first day of illness that persisted for 2–4 days; 2) a recovery phase that peaked on day 4 and day 6 after virus infection; 3) restoration of baseline gene expression patterns by day 21. A full list of the 202 transcript probes in the heatmaps and their corresponding genes is provided in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004869#ppat.1004869.s009\" target=\"_blank\">S1 Table</a>. <b>(F-G)</b> Expression changes of <b>(F)</b><i>IFI27</i> and <b>(G)</b><i>PI3</i> discriminate between infections with influenza virus and rhinovirus. Fold Changes of <i>IFI27</i> and <i>PI3</i> were measured in paired day 0 –baseline samples from patients with ARI. Subjects were grouped by infections status. Enterovirus, HKU1, NL63, and RSV infections were grouped together as “Other” virus. One-way ANOVA was used to determine whether there are any significant differences between influenza virus infection groups (Grey) and each non-influenza virus group (Black). ***, P <0.001; **, P <0.005; *, P <0.01.</p>", "links"=>[], "tags"=>["expression signature", "64 influenza", "7 timepoints", "immunity genes", "T lymphocyte depressions", "NK cells", "novel gene expression correlates", "Blood Gene Expression", "5 illness visits", "interferon pathway", "influenza virus infection", "Rhinovirus infection", "Cell proliferation", "9 influenza B", "day 21", "days 4", "gene expression pattern", "study visits", "blood microarray gene expression data", "recovery phase", "gene modules", "142 subjects", "Prospective Cohort Study", "cell composition scores", "data show", "host transcriptional response"], "article_id"=>1448048, "categories"=>["Biological Sciences"], "users"=>["Yijie Zhai", "Luis M. Franco", "Robert L. Atmar", "John M. Quarles", "Nancy Arden", "Kristine L. Bucasas", "Janet M. Wells", "Diane Niño", "Xueqing Wang", "Gladys E. Zapata", "Chad A. Shaw", "John W. Belmont", "Robert B. Couch"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004869.g002", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_robust_and_dynamic_host_transcriptional_response_to_influenza_virus_infection_/1448048", "title"=>"A robust and dynamic host transcriptional response to influenza virus infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-12 03:45:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/2109337", "https://ndownloader.figshare.com/files/2109338", "https://ndownloader.figshare.com/files/2109339", "https://ndownloader.figshare.com/files/2109340", "https://ndownloader.figshare.com/files/2109341", "https://ndownloader.figshare.com/files/2109342", "https://ndownloader.figshare.com/files/2109343", "https://ndownloader.figshare.com/files/2109344", "https://ndownloader.figshare.com/files/2109345", "https://ndownloader.figshare.com/files/2109346", "https://ndownloader.figshare.com/files/2109347", "https://ndownloader.figshare.com/files/2109348", "https://ndownloader.figshare.com/files/2109349"], "description"=>"<div><p>To better understand the systemic response to naturally acquired acute respiratory viral infections, we prospectively enrolled 1610 healthy adults in 2009 and 2010. Of these, 142 subjects were followed for detailed evaluation of acute viral respiratory illness. We examined peripheral blood gene expression at 7 timepoints: enrollment, 5 illness visits and the end of each year of the study. 133 completed all study visits and yielded technically adequate peripheral blood microarray gene expression data. Seventy-three (55%) had an influenza virus infection, 64 influenza A and 9 influenza B. The remaining subjects had a rhinovirus infection (N = 32), other viral infections (N = 4), or no viral agent identified (N = 24). The results, which were replicated between two seasons, showed a dramatic upregulation of interferon pathway and innate immunity genes. This persisted for 2-4 days. The data show a recovery phase at days 4 and 6 with differentially expressed transcripts implicated in cell proliferation and repair. By day 21 the gene expression pattern was indistinguishable from baseline (enrollment). Influenza virus infection induced a higher magnitude and longer duration of the shared expression signature of illness compared to the other viral infections. Using lineage and activation state-specific transcripts to produce cell composition scores, patterns of B and T lymphocyte depressions accompanied by a major activation of NK cells were detected in the acute phase of illness. The data also demonstrate multiple dynamic gene modules that are reorganized and strengthened following infection. Finally, we examined pre- and post-infection anti-influenza antibody titers defining novel gene expression correlates.</p></div>", "links"=>[], "tags"=>["expression signature", "64 influenza", "7 timepoints", "immunity genes", "T lymphocyte depressions", "NK cells", "novel gene expression correlates", "Blood Gene Expression", "5 illness visits", "interferon pathway", "influenza virus infection", "Rhinovirus infection", "Cell proliferation", "9 influenza B", "day 21", "days 4", "gene expression pattern", "study visits", "blood microarray gene expression data", "recovery phase", "gene modules", "142 subjects", "Prospective Cohort Study", "cell composition scores", "data show", "host transcriptional response"], "article_id"=>1448081, "categories"=>["Biological Sciences"], "users"=>["Yijie Zhai", "Luis M. Franco", "Robert L. Atmar", "John M. Quarles", "Nancy Arden", "Kristine L. Bucasas", "Janet M. Wells", "Diane Niño", "Xueqing Wang", "Gladys E. Zapata", "Chad A. Shaw", "John W. Belmont", "Robert B. Couch"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1004869.s001", "https://dx.doi.org/10.1371/journal.ppat.1004869.s002", "https://dx.doi.org/10.1371/journal.ppat.1004869.s003", "https://dx.doi.org/10.1371/journal.ppat.1004869.s004", "https://dx.doi.org/10.1371/journal.ppat.1004869.s005", "https://dx.doi.org/10.1371/journal.ppat.1004869.s006", "https://dx.doi.org/10.1371/journal.ppat.1004869.s007", "https://dx.doi.org/10.1371/journal.ppat.1004869.s008", "https://dx.doi.org/10.1371/journal.ppat.1004869.s009", "https://dx.doi.org/10.1371/journal.ppat.1004869.s010", "https://dx.doi.org/10.1371/journal.ppat.1004869.s011", "https://dx.doi.org/10.1371/journal.ppat.1004869.s012", "https://dx.doi.org/10.1371/journal.ppat.1004869.s013"], "stats"=>{"downloads"=>41, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Host_Transcriptional_Response_to_Influenza_and_Other_Acute_Respiratory_Viral_Infections_8211_A_Prospective_Cohort_Study_/1448081", "title"=>"Host Transcriptional Response to Influenza and Other Acute Respiratory Viral Infections – A Prospective Cohort Study", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-06-12 03:45:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/2109307"], "description"=>"<p>DAVID was used to identify over-represented Gene Ontology terms among <b>(A)</b> up-regulated genes and <b>(B)</b> down-regulated genes on each day (BH-corrected <i>P</i> values <0.05 in both 2009 and 2010 cohorts). The length of the bar (x-axis) represents the–log<sub>10</sub> (Benjamini-adj.<i>P</i> value). The bars are colored by day.</p>", "links"=>[], "tags"=>["expression signature", "64 influenza", "7 timepoints", "immunity genes", "T lymphocyte depressions", "NK cells", "novel gene expression correlates", "Blood Gene Expression", "5 illness visits", "interferon pathway", "influenza virus infection", "Rhinovirus infection", "Cell proliferation", "9 influenza B", "day 21", "days 4", "gene expression pattern", "study visits", "blood microarray gene expression data", "recovery phase", "gene modules", "142 subjects", "Prospective Cohort Study", "cell composition scores", "data show", "host transcriptional response"], "article_id"=>1448053, "categories"=>["Biological Sciences"], "users"=>["Yijie Zhai", "Luis M. Franco", "Robert L. Atmar", "John M. Quarles", "Nancy Arden", "Kristine L. Bucasas", "Janet M. Wells", "Diane Niño", "Xueqing Wang", "Gladys E. Zapata", "Chad A. Shaw", "John W. Belmont", "Robert B. Couch"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004869.g004", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Top_GO_terms_enriched_in_differentially_expressed_genes_over_the_course_of_6_days_after_influenza_virus_infection_/1448053", "title"=>"Top GO terms enriched in differentially expressed genes over the course of 6 days after influenza virus infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-12 03:45:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/2109308"], "description"=>"<p><b>(A-D)</b> Groups, or modules, of co-regulated DEGs were identified by WGCNA. Representative Gene Ontology (GO) categories for each module were identified by functional enrichment analysis and shown in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004869#ppat.1004869.t006\" target=\"_blank\">Table 6</a>. Module expression patterns across different time points were represented by violin plots of log<sub>2</sub> fold-change in gene expression relative to baseline. <b>(E-H)</b> Pscan was used to scan the promoter regions of all genes in each module and identify the over-represented transcription factor binding sites (TFBS). The predicted transcription factors, which marked in red and their target genes (z-score > 2) were connected by edges in the networks.</p>", "links"=>[], "tags"=>["expression signature", "64 influenza", "7 timepoints", "immunity genes", "T lymphocyte depressions", "NK cells", "novel gene expression correlates", "Blood Gene Expression", "5 illness visits", "interferon pathway", "influenza virus infection", "Rhinovirus infection", "Cell proliferation", "9 influenza B", "day 21", "days 4", "gene expression pattern", "study visits", "blood microarray gene expression data", "recovery phase", "gene modules", "142 subjects", "Prospective Cohort Study", "cell composition scores", "data show", "host transcriptional response"], "article_id"=>1448054, "categories"=>["Biological Sciences"], "users"=>["Yijie Zhai", "Luis M. Franco", "Robert L. Atmar", "John M. Quarles", "Nancy Arden", "Kristine L. Bucasas", "Janet M. Wells", "Diane Niño", "Xueqing Wang", "Gladys E. Zapata", "Chad A. Shaw", "John W. Belmont", "Robert B. Couch"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004869.g005", "stats"=>{"downloads"=>21, "page_views"=>427, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TF_networks_within_the_WGCNA_modules_over_the_course_of_influenza_illness_/1448054", "title"=>"TF networks within the WGCNA modules over the course of influenza illness.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-12 03:45:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/2109314"], "description"=>"<p><b>(A)</b> In the comparative correlation heatmap, the upper diagonal of the main matrix shows a correlation between pairs of genes among samples collected from the individuals after influenza virus infection (Left: Day 0, Right: Day 4). The lower diagonal of the heatmap shows a correlation between the same gene pairs in these individuals on baseline. Red color corresponds to positive correlations, and blue corresponds to negative correlations. <b>(B)</b> Changes in the correlation between genes <i>OAS2</i> and <i>RNASEL</i>. Each dot corresponds to an individual and the axes mark the log<sub>2</sub> expression values of the two transcripts in that individual. The genes are uncorrelated on baseline (<i>r</i> = -0.01) but are positively correlated on day 0 (<i>r</i> = 0.72, <i>P</i> <0.001), and this correlation became attenuated on day 4 (<i>r</i> = 0.09).</p>", "links"=>[], "tags"=>["expression signature", "64 influenza", "7 timepoints", "immunity genes", "T lymphocyte depressions", "NK cells", "novel gene expression correlates", "Blood Gene Expression", "5 illness visits", "interferon pathway", "influenza virus infection", "Rhinovirus infection", "Cell proliferation", "9 influenza B", "day 21", "days 4", "gene expression pattern", "study visits", "blood microarray gene expression data", "recovery phase", "gene modules", "142 subjects", "Prospective Cohort Study", "cell composition scores", "data show", "host transcriptional response"], "article_id"=>1448058, "categories"=>["Biological Sciences"], "users"=>["Yijie Zhai", "Luis M. Franco", "Robert L. Atmar", "John M. Quarles", "Nancy Arden", "Kristine L. Bucasas", "Janet M. Wells", "Diane Niño", "Xueqing Wang", "Gladys E. Zapata", "Chad A. Shaw", "John W. Belmont", "Robert B. Couch"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004869.g006", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Host_gene_network_connectivity_became_stronger_after_the_subjects_were_infected_with_influenza_virus_/1448058", "title"=>"Host gene network connectivity became stronger after the subjects were infected with influenza virus.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-12 03:45:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/2109315"], "description"=>"<p><b>(Left)</b> Each individual is represented by a column in the heatmaps. The top heatmap displays the magnitude of the antibody response (delta titer). The bottom heatmaps display the deviations around the expression mean for each transcript. <b>(Right)</b><i>LILRB4</i> showed the greatest positive correlation (<i>r</i> = 0.42, <i>P</i> <0.005) and <i>FOXO3</i> showed the greatest negative correlation (<i>r</i> = -0.48, <i>P</i> <0.001) between gene expression on day 0 and the magnitude of the antibody response to influenza virus infection.</p>", "links"=>[], "tags"=>["expression signature", "64 influenza", "7 timepoints", "immunity genes", "T lymphocyte depressions", "NK cells", "novel gene expression correlates", "Blood Gene Expression", "5 illness visits", "interferon pathway", "influenza virus infection", "Rhinovirus infection", "Cell proliferation", "9 influenza B", "day 21", "days 4", "gene expression pattern", "study visits", "blood microarray gene expression data", "recovery phase", "gene modules", "142 subjects", "Prospective Cohort Study", "cell composition scores", "data show", "host transcriptional response"], "article_id"=>1448059, "categories"=>["Biological Sciences"], "users"=>["Yijie Zhai", "Luis M. Franco", "Robert L. Atmar", "John M. Quarles", "Nancy Arden", "Kristine L. Bucasas", "Janet M. Wells", "Diane Niño", "Xueqing Wang", "Gladys E. Zapata", "Chad A. Shaw", "John W. Belmont", "Robert B. Couch"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004869.g007", "stats"=>{"downloads"=>0, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_total_of_229_genes_showed_evidence_of_significant_correlation_between_gene_expression_and_the_antibody_response_/1448059", "title"=>"A total of 229 genes showed evidence of significant correlation between gene expression and the antibody response.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-12 03:45:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/2109316"], "description"=>"<p><b>*</b>Influenza A = Influenza Virus type A; Influenza B = Influenza Virus type B; HRV = Human rhinovirus; RSVA = Respiratory Syncytial Virus type A; RSVB = Respiratory Syncytial Virus type B; OC43 = Human coronavirus OC43; 229E = Human coronavirus 229E; NL63 = Human coronavirus NL63; HKU1 = Human coronavirus HKU1; Entero = Enterovirus; Unknown: Our tests did not detect one of the viruses sought.</p><p>Viral infections and demographic information of the 133 subjects with influenza-like illness enrolled at Texas A&M University in Fall 2009 and 2010 from whom microarray expression data were available.</p>", "links"=>[], "tags"=>["expression signature", "64 influenza", "7 timepoints", "immunity genes", "T lymphocyte depressions", "NK cells", "novel gene expression correlates", "Blood Gene Expression", "5 illness visits", "interferon pathway", "influenza virus infection", "Rhinovirus infection", "Cell proliferation", "9 influenza B", "day 21", "days 4", "gene expression pattern", "study visits", "blood microarray gene expression data", "recovery phase", "gene modules", "142 subjects", "Prospective Cohort Study", "cell composition scores", "data show", "host transcriptional response"], "article_id"=>1448060, "categories"=>["Biological Sciences"], "users"=>["Yijie Zhai", "Luis M. Franco", "Robert L. Atmar", "John M. Quarles", "Nancy Arden", "Kristine L. Bucasas", "Janet M. Wells", "Diane Niño", "Xueqing Wang", "Gladys E. Zapata", "Chad A. Shaw", "John W. Belmont", "Robert B. Couch"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004869.t001", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Viral_infections_and_demographic_information_of_the_133_subjects_with_influenza_like_illness_enrolled_at_Texas_A_amp_M_University_in_Fall_2009_and_2010_from_whom_microarray_expression_data_were_available_/1448060", "title"=>"Viral infections and demographic information of the 133 subjects with influenza-like illness enrolled at Texas A&M University in Fall 2009 and 2010 from whom microarray expression data were available.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-06-12 03:45:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/2109317"], "description"=>"<p>Top upregulated genes in the acute phase of influenza virus infection.</p>", "links"=>[], "tags"=>["expression signature", "64 influenza", "7 timepoints", "immunity genes", "T lymphocyte depressions", "NK cells", "novel gene expression correlates", "Blood Gene Expression", "5 illness visits", "interferon pathway", "influenza virus infection", "Rhinovirus infection", "Cell proliferation", "9 influenza B", "day 21", "days 4", "gene expression pattern", "study visits", "blood microarray gene expression data", "recovery phase", "gene modules", "142 subjects", "Prospective Cohort Study", "cell composition scores", "data show", "host transcriptional response"], "article_id"=>1448061, "categories"=>["Biological Sciences"], "users"=>["Yijie Zhai", "Luis M. Franco", "Robert L. Atmar", "John M. Quarles", "Nancy Arden", "Kristine L. Bucasas", "Janet M. Wells", "Diane Niño", "Xueqing Wang", "Gladys E. Zapata", "Chad A. Shaw", "John W. Belmont", "Robert B. Couch"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004869.t002", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Top_upregulated_genes_in_the_acute_phase_of_influenza_virus_infection_/1448061", "title"=>"Top upregulated genes in the acute phase of influenza virus infection.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-06-12 03:45:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/2109318"], "description"=>"<p>Top downregulated genes in the acute phase of influenza virus infection.</p>", "links"=>[], "tags"=>["expression signature", "64 influenza", "7 timepoints", "immunity genes", "T lymphocyte depressions", "NK cells", "novel gene expression correlates", "Blood Gene Expression", "5 illness visits", "interferon pathway", "influenza virus infection", "Rhinovirus infection", "Cell proliferation", "9 influenza B", "day 21", "days 4", "gene expression pattern", "study visits", "blood microarray gene expression data", "recovery phase", "gene modules", "142 subjects", "Prospective Cohort Study", "cell composition scores", "data show", "host transcriptional response"], "article_id"=>1448062, "categories"=>["Biological Sciences"], "users"=>["Yijie Zhai", "Luis M. Franco", "Robert L. Atmar", "John M. Quarles", "Nancy Arden", "Kristine L. Bucasas", "Janet M. Wells", "Diane Niño", "Xueqing Wang", "Gladys E. Zapata", "Chad A. Shaw", "John W. Belmont", "Robert B. Couch"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004869.t003", "stats"=>{"downloads"=>2, "page_views"=>25, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Top_downregulated_genes_in_the_acute_phase_of_influenza_virus_infection_/1448062", "title"=>"Top downregulated genes in the acute phase of influenza virus infection.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-06-12 03:45:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/2109319"], "description"=>"<p>Top upregulated genes in the recovery phase of influenza virus infection.</p>", "links"=>[], "tags"=>["expression signature", "64 influenza", "7 timepoints", "immunity genes", "T lymphocyte depressions", "NK cells", "novel gene expression correlates", "Blood Gene Expression", "5 illness visits", "interferon pathway", "influenza virus infection", "Rhinovirus infection", "Cell proliferation", "9 influenza B", "day 21", "days 4", "gene expression pattern", "study visits", "blood microarray gene expression data", "recovery phase", "gene modules", "142 subjects", "Prospective Cohort Study", "cell composition scores", "data show", "host transcriptional response"], "article_id"=>1448063, "categories"=>["Biological Sciences"], "users"=>["Yijie Zhai", "Luis M. Franco", "Robert L. Atmar", "John M. Quarles", "Nancy Arden", "Kristine L. Bucasas", "Janet M. Wells", "Diane Niño", "Xueqing Wang", "Gladys E. Zapata", "Chad A. Shaw", "John W. Belmont", "Robert B. Couch"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004869.t004", "stats"=>{"downloads"=>6, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Top_upregulated_genes_in_the_recovery_phase_of_influenza_virus_infection_/1448063", "title"=>"Top upregulated genes in the recovery phase of influenza virus infection.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-06-12 03:45:43"}

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{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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