A Bovine Lymphosarcoma Cell Line Infected with Theileria annulata Exhibits an Irreversible Reconfiguration of Host Cell Gene Expression
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{"title"=>"A Bovine Lymphosarcoma Cell Line Infected with Theileria annulata Exhibits an Irreversible Reconfiguration of Host Cell Gene Expression", "type"=>"journal", "authors"=>[{"first_name"=>"Jane H.", "last_name"=>"Kinnaird", "scopus_author_id"=>"7004025183"}, {"first_name"=>"William", "last_name"=>"Weir", "scopus_author_id"=>"34574247100"}, {"first_name"=>"Zeeshan", "last_name"=>"Durrani", "scopus_author_id"=>"55224505800"}, {"first_name"=>"Sreerekha S.", "last_name"=>"Pillai", "scopus_author_id"=>"35752534300"}, {"first_name"=>"Margaret", "last_name"=>"Baird", "scopus_author_id"=>"57196832421"}, {"first_name"=>"Brian R.", "last_name"=>"Shiels", "scopus_author_id"=>"7003503831"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"369200456", "sgr"=>"84879489002", "issn"=>"19326203", "pmid"=>"23840536", "scopus"=>"2-s2.0-84879489002", "doi"=>"10.1371/journal.pone.0066833", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"ce119f0b-f89c-3a9b-a84d-bf8064e31764", "abstract"=>"Theileria annulata, an intracellular parasite of bovine lymphoid cells, induces substantial phenotypic alterations to its host cell including continuous proliferation, cytoskeletal changes and resistance to apoptosis. While parasite induced modulation of host cell signal transduction pathways and NFκB activation are established, there remains considerable speculation on the complexities of the parasite directed control mechanisms that govern these radical changes to the host cell. Our objectives in this study were to provide a comprehensive analysis of the global changes to host cell gene expression with emphasis on those that result from direct intervention by the parasite. By using comparative microarray analysis of an uninfected bovine cell line and its Theileria infected counterpart, in conjunction with use of the specific parasitacidal agent, buparvaquone, we have identified a large number of host cell gene expression changes that result from parasite infection. Our results indicate that the viable parasite can irreversibly modify the transformed phenotype of a bovine cell line. Fifty percent of genes with altered expression failed to show a reversible response to parasite death, a possible contributing factor to initiation of host cell apoptosis. The genes that did show an early predicted response to loss of parasite viability highlighted a sub-group of genes that are likely to be under direct control by parasite infection. Network and pathway analysis demonstrated that this sub-group is significantly enriched for genes involved in regulation of chromatin modification and gene expression. The results provide evidence that the Theileria parasite has the regulatory capacity to generate widespread change to host cell gene expression in a complex and largely irreversible manner.", "link"=>"http://www.mendeley.com/research/bovine-lymphosarcoma-cell-line-infected-theileria-annulata-exhibits-irreversible-reconfiguration-hos", "reader_count"=>13, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Researcher"=>1, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>5, "Other"=>1, "Student > Master"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Researcher"=>1, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>5, "Other"=>1, "Student > Master"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>6, "Veterinary Science and Veterinary Medicine"=>1, "Physics and Astronomy"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>6}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"United States"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1101918"], "description"=>"<p>Top ranking genes with (A) elevated (+) or (B) repressed (−) expression in parasite infected TBL20 compared uninfected BL20 cells. Fold change (FC) and the direction of any BW720c response (+, up; –, down; blank no change) are indicated. Differential expression was determined by RP analysis using a FDR cut-off of 5%.</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome expression analysis", "Molecular genetics", "gene expression", "microarrays", "genetics", "Gene function", "Genome analysis tools", "Genetic networks", "transcriptomes", "microbiology", "Parasitology", "Zoology", "Infectious diseases", "Parasitic diseases", "Veterinary diseases", "Veterinary parasitology", "genes", "elevated", "repressed", "tbl20", "compared"], "article_id"=>732173, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Jane H. Kinnaird", "William Weir", "Zeeshan Durrani", "Sreerekha S. Pillai", "Margaret Baird", "Brian R. Shiels"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066833.t002", "stats"=>{"downloads"=>3, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Top_ranking_genes_elevated_or_repressed_in_TBL20_compared_to_BL20_/732173", "title"=>"Top-ranking genes elevated or repressed in TBL20 compared to BL20.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-26 08:45:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/1101917"], "description"=>"<p>Illustration of the target gene network from our analysis where differential expression may result from activation or inhibition of 3 transcription regulators, CLOCK, SCREB and XBP1, each with activation status predicted to be altered by parasite infection and reversed by BW720c in our analysis (see text). Red means up-regulated in TBL20 compared to BL20 (range 1.7–117 fold); green is down-regulated in TBL20 (range 1.7–110 fold); grey, no differential expression.</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome expression analysis", "Molecular genetics", "gene expression", "microarrays", "genetics", "Gene function", "Genome analysis tools", "Genetic networks", "transcriptomes", "microbiology", "Parasitology", "Zoology", "Infectious diseases", "Parasitic diseases", "Veterinary diseases", "Veterinary parasitology", "screb", "xbp1", "transcriptional", "altered", "activities", "tbl20", "reversed", "genes"], "article_id"=>732172, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Jane H. Kinnaird", "William Weir", "Zeeshan Durrani", "Sreerekha S. Pillai", "Margaret Baird", "Brian R. Shiels"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066833.g009", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CLOCK_SCREB_and_XBP1_transcriptional_regulators_predicted_to_have_altered_activities_in_TBL20_that_are_reversed_in_the_presence_of_BW720c_have_target_genes_in_common_/732172", "title"=>"CLOCK, SCREB and XBP1 transcriptional regulators, predicted to have altered activities in TBL20 that are reversed in the presence of BW720c, have target genes in common.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-26 08:45:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/1101913"], "description"=>"<p>Western analysis of total protein cell extracts from uninfected (BL20) and infected (TBL20) cells treated with BW720c for 0 (−), 24, 48 and 72 (+) hours. Equal protein loadings were verified by Ponceau S staining. Host HDAC9, HDAC2 and NFκB2 are shown relative to constitutive tubulin and actin. Antibodies are as described in Methods section.</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome expression analysis", "Molecular genetics", "gene expression", "microarrays", "genetics", "Gene function", "Genome analysis tools", "Genetic networks", "transcriptomes", "microbiology", "Parasitology", "Zoology", "Infectious diseases", "Parasitic diseases", "Veterinary diseases", "Veterinary parasitology", "profiles", "hdac9", "genes", "reflected"], "article_id"=>732168, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Jane H. Kinnaird", "William Weir", "Zeeshan Durrani", "Sreerekha S. Pillai", "Margaret Baird", "Brian R. Shiels"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066833.g007", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Microarray_expression_profiles_of_HDAC9_and_NF_954_B2_genes_are_also_reflected_at_protein_level_/732168", "title"=>"Microarray expression profiles of HDAC9 and NFκB2 genes are also reflected at protein level.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-26 08:45:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/1101908"], "description"=>"<p>A comparative analysis for enrichment in cellular molecular functions was carried out for each dataset. Fundamental cellular molecular functions contained within the IPA database and above the threshold for significance (-log(p value), p = 0.05) were selected for comparison. Black bars, enrichment inTBL20 compared to BL20; mid-grey, TBL20 at 24 h BW720c compared to TBL20 control; light-grey bars, TBL20 at 48 h BW720c compared to TBL20 control.</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome expression analysis", "Molecular genetics", "gene expression", "microarrays", "genetics", "Gene function", "Genome analysis tools", "Genetic networks", "transcriptomes", "microbiology", "Parasitology", "Zoology", "Infectious diseases", "Parasitic diseases", "Veterinary diseases", "Veterinary parasitology", "genes", "parasite", "bw720c", "enriched", "molecular"], "article_id"=>732163, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Jane H. Kinnaird", "William Weir", "Zeeshan Durrani", "Sreerekha S. Pillai", "Margaret Baird", "Brian R. Shiels"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066833.g005", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differentially_expressed_genes_in_parasite_infection_and_after_BW720c_treatment_are_enriched_for_fundamental_molecular_functions_/732163", "title"=>"Differentially expressed genes in parasite infection and after BW720c treatment are enriched for fundamental molecular functions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-26 08:45:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/1101922"], "description"=>"<p>The predictions of activation or inhibition of transcription regulators are based on the direction of expression of differentially expressed known target genes collated in the IPA database. Cut-off criteria, Z score >2 for activation and <−2 for inhibition. * indicates those predictions that are most significant based on p value. Target gene ratio represents the number of genes expressed in a direction consistent with the prediction over the total number of target genes for that transcription regulator identified in the database. ** SMARCB1 is predicted to be activated at 24 <i>and</i> 48 h as a direct result of parasite inhibition by BW720c.</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome expression analysis", "Molecular genetics", "gene expression", "microarrays", "genetics", "Gene function", "Genome analysis tools", "Genetic networks", "transcriptomes", "microbiology", "Parasitology", "Zoology", "Infectious diseases", "Parasitic diseases", "Veterinary diseases", "Veterinary parasitology", "regulators", "activation", "reversed", "bw720c"], "article_id"=>732177, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Jane H. Kinnaird", "William Weir", "Zeeshan Durrani", "Sreerekha S. Pillai", "Margaret Baird", "Brian R. Shiels"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066833.t005", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Transcription_regulators_where_the_predicted_activation_status_is_reversed_following_BW720c_exposure_/732177", "title"=>"Transcription regulators where the predicted activation status is reversed following BW720c exposure.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-26 08:45:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/1101920"], "description"=>"<p>Summary of the total numbers of bovine genes in the dataset where expression is altered by the presence of the <i>Theileria</i> parasite (TBL20 cells) compared to uninfected BL20 cells and the overall response following BW720c treatment of TBL20 cells to kill the parasite. Differentially expressed gene sets were derived by Rank Product analysis (FDR <5%). *This gene set included only genes for which there was no evidence for differential expression by RP analysis.</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome expression analysis", "Molecular genetics", "gene expression", "microarrays", "genetics", "Gene function", "Genome analysis tools", "Genetic networks", "transcriptomes", "microbiology", "Parasitology", "Zoology", "Infectious diseases", "Parasitic diseases", "Veterinary diseases", "Veterinary parasitology"], "article_id"=>732175, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Jane H. Kinnaird", "William Weir", "Zeeshan Durrani", "Sreerekha S. Pillai", "Margaret Baird", "Brian R. Shiels"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066833.t001", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Overall_gene_expression_changes_for_different_experimental_conditions_/732175", "title"=>"Overall gene expression changes for different experimental conditions.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-26 08:45:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/1101921"], "description"=>"<p>Various components of the AP1 transcription factor complex that were elevated (+) in TBL20 or repressed (−) in TBL20 compared to BL20. The BW720c response is indicated to the right. The FDR generated by RP for FOSB* and ATF7IP** in TBL20 compared to BL20 were above our normal threshold of 5% but were included in this table as both showed a strong reversible BW720c response.</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome expression analysis", "Molecular genetics", "gene expression", "microarrays", "genetics", "Gene function", "Genome analysis tools", "Genetic networks", "transcriptomes", "microbiology", "Parasitology", "Zoology", "Infectious diseases", "Parasitic diseases", "Veterinary diseases", "Veterinary parasitology", "sub-units", "altered", "tbl20", "compared"], "article_id"=>732176, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Jane H. Kinnaird", "William Weir", "Zeeshan Durrani", "Sreerekha S. Pillai", "Margaret Baird", "Brian R. Shiels"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066833.t004", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_AP1_sub_units_with_altered_expression_in_TBL20_compared_to_BL20_/732176", "title"=>"AP1 sub-units with altered expression in TBL20 compared to BL20.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-26 08:45:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/1101902"], "description"=>"<p><b>A. Caspase 3/7 activity in BW720c-treated uninfected BL20 and infected TBL20.</b> Caspase 3/7 activity was assayed on samples of 10<sup>4</sup> cells taken from triplicate cultures for each cellular condition; BL 20 and TBL20, untreated and treated with BW720c for 24 and 48 h. Error bars represent the standard deviation from the mean. <b>B. Heat map illustration of the relative expression levels for parasite house-keeping genes before and after exposure to BW720c for 24 and 48 </b><b>h</b> 106 parasite house-keeping genes were randomly selected based on their annotation. The majority of parasite genes show considerably decreased levels by 24 h. Expression level range is 3.9 (blue, low) to 14.9 (red, high). Values are log<sub>2</sub>. <b>C. Western analysis demonstrated that expression of parasite proteins Tasp and TA10720 decreased during exposure to BW720c</b> Total protein cell extracts were prepared from untreated BL20 and TBL20 (−) and in TBL20 cells at 24 and 72 (+) hours after addition of BW72c. Equal protein loadings were verified by Ponceau S staining. Parasite proteins, Tasp (schizont surface) and TA10720 (HSP90-related, schizont organelle) are shown relative to constitutive bovine actin. Antibodies are as described in methods section.</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome expression analysis", "Molecular genetics", "gene expression", "microarrays", "genetics", "Gene function", "Genome analysis tools", "Genetic networks", "transcriptomes", "microbiology", "Parasitology", "Zoology", "Infectious diseases", "Parasitic diseases", "Veterinary diseases", "Veterinary parasitology"], "article_id"=>732157, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Jane H. Kinnaird", "William Weir", "Zeeshan Durrani", "Sreerekha S. Pillai", "Margaret Baird", "Brian R. Shiels"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066833.g002", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Figure_2_/732157", "title"=>"Figure 2", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-26 08:45:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/1101919"], "description"=>"<p>Transcription regulators identified in the Ingenuity Pathway Analysis Database (IPA) that were differentially expressed in TBL20 compared to BL20 (FDR 5%). The fold change in TBL20 relative to BL20 is indicated; +, elevated in TBL20; –, repressed in TBL20. The fold change response in TBL20 treated with BW720c relative to TBL20 (FDR 5%) is indicated to the right. The top 15 ranking transcriptional regulations, both elevated and repressed, are shown grouped according to BW720c response.</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome expression analysis", "Molecular genetics", "gene expression", "microarrays", "genetics", "Gene function", "Genome analysis tools", "Genetic networks", "transcriptomes", "microbiology", "Parasitology", "Zoology", "Infectious diseases", "Parasitic diseases", "Veterinary diseases", "Veterinary parasitology", "regulators", "elevated", "repressed", "tbl20", "compared"], "article_id"=>732174, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Jane H. Kinnaird", "William Weir", "Zeeshan Durrani", "Sreerekha S. Pillai", "Margaret Baird", "Brian R. Shiels"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066833.t003", "stats"=>{"downloads"=>9, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Transcription_regulators_elevated_or_repressed_in_TBL20_compared_to_BL20_/732174", "title"=>"Transcription regulators elevated or repressed in TBL20 compared to BL20.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-26 08:45:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/1101916"], "description"=>"<p><b>A. Transcriptional control defined for the RAG1/2 locus showing points of regulation in Theileria infected cells</b> Prediction of expression level was as defined in the methods section; (VH), very high; (H), high. <b>–</b> to the left of the gene symbol, no predicted change in TBL20 compared to BL20. <b>–</b> to the right of the gene symbol, no change in BW720c. ▴<b>▾</b>, elevated or repressed in TBL20 (to the left) or BW720c (to the right) of the gene symbol. <b>B. Modulation of an established BL20 transcription factor network by parasite infection</b> Components of the MYB transcription factor network within different cellular compartments that show altered expression in TBL20 compared to BL20. Green, repressed expression in TBL20; red, elevated expression in TBL20.</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome expression analysis", "Molecular genetics", "gene expression", "microarrays", "genetics", "Gene function", "Genome analysis tools", "Genetic networks", "transcriptomes", "microbiology", "Parasitology", "Zoology", "Infectious diseases", "Parasitic diseases", "Veterinary diseases", "Veterinary parasitology"], "article_id"=>732171, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Jane H. Kinnaird", "William Weir", "Zeeshan Durrani", "Sreerekha S. Pillai", "Margaret Baird", "Brian R. Shiels"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066833.g008", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Figure_8_/732171", "title"=>"Figure 8", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-26 08:45:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/1101901"], "description"=>"<p>Comparison of growth rates of uninfected (BL20) and infected (TBL20) cell lines in the presence and absence of BW720c at 50 ng ml<sup>−1</sup>. Culturing was as described in Methods section. All cultures were counted daily with three replicate cultures used for each condition. Error bars represent standard deviations from the mean for each time point. Solid lines, non-drug treated cultures; dashed lines, BW720c treated; thin line, BL20 and thick line, TBL20.</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome expression analysis", "Molecular genetics", "gene expression", "microarrays", "genetics", "Gene function", "Genome analysis tools", "Genetic networks", "transcriptomes", "microbiology", "Parasitology", "Zoology", "Infectious diseases", "Parasitic diseases", "Veterinary diseases", "Veterinary parasitology", "rates", "bl20", "tbl20", "lines", "bw720c"], "article_id"=>732156, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Jane H. Kinnaird", "William Weir", "Zeeshan Durrani", "Sreerekha S. Pillai", "Margaret Baird", "Brian R. Shiels"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066833.g001", "stats"=>{"downloads"=>0, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparative_growth_rates_of_BL20_and_TBL20_cell_lines_during_BW720c_treatment_/732156", "title"=>"Comparative growth rates of BL20 and TBL20 cell lines during BW720c treatment.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-26 08:45:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/1101910"], "description"=>"<p>Enriched Canonical Pathways for comparisons, BL20 vs TBL20; TBL20 vs TBL20_24 h_BW720c; TBL20 vs TBL20_48 h_BW720c were selected from the top 12 defined in each comparison. Top chart, BL20 compared to TBL20; middle chart, TBL20 at 24 h BW720c compared to TBL20 control; bottom chart, TBL20 at 48 h BW720c compared to TBL20. The significance of the enrichment is indicted in each case (-log(p value).</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome expression analysis", "Molecular genetics", "gene expression", "microarrays", "genetics", "Gene function", "Genome analysis tools", "Genetic networks", "transcriptomes", "microbiology", "Parasitology", "Zoology", "Infectious diseases", "Parasitic diseases", "Veterinary diseases", "Veterinary parasitology", "canonical"], "article_id"=>732165, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Jane H. Kinnaird", "William Weir", "Zeeshan Durrani", "Sreerekha S. Pillai", "Margaret Baird", "Brian R. Shiels"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066833.g006", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Enrichment_in_canonical_pathways_/732165", "title"=>"Enrichment in canonical pathways.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-26 08:45:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/1101924", "https://ndownloader.figshare.com/files/1101929", "https://ndownloader.figshare.com/files/1101930", "https://ndownloader.figshare.com/files/1101931", "https://ndownloader.figshare.com/files/1101932", "https://ndownloader.figshare.com/files/1101936", "https://ndownloader.figshare.com/files/1101947", "https://ndownloader.figshare.com/files/1101951", "https://ndownloader.figshare.com/files/1101969", "https://ndownloader.figshare.com/files/1101977", "https://ndownloader.figshare.com/files/1101990"], "description"=>"<div><p><i>Theileria annulata</i>, an intracellular parasite of bovine lymphoid cells, induces substantial phenotypic alterations to its host cell including continuous proliferation, cytoskeletal changes and resistance to apoptosis. While parasite induced modulation of host cell signal transduction pathways and NFκB activation are established, there remains considerable speculation on the complexities of the parasite directed control mechanisms that govern these radical changes to the host cell. Our objectives in this study were to provide a comprehensive analysis of the global changes to host cell gene expression with emphasis on those that result from direct intervention by the parasite. By using comparative microarray analysis of an uninfected bovine cell line and its <i>Theileria</i> infected counterpart, in conjunction with use of the specific parasitacidal agent, buparvaquone, we have identified a large number of host cell gene expression changes that result from parasite infection. Our results indicate that the viable parasite can irreversibly modify the transformed phenotype of a bovine cell line. Fifty percent of genes with altered expression failed to show a reversible response to parasite death, a possible contributing factor to initiation of host cell apoptosis. The genes that did show an early predicted response to loss of parasite viability highlighted a sub-group of genes that are likely to be under direct control by parasite infection. Network and pathway analysis demonstrated that this sub-group is significantly enriched for genes involved in regulation of chromatin modification and gene expression. The results provide evidence that the <i>Theileria</i> parasite has the regulatory capacity to generate widespread change to host cell gene expression in a complex and largely irreversible manner.</p></div>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome expression analysis", "Molecular genetics", "gene expression", "microarrays", "genetics", "Gene function", "Genome analysis tools", "Genetic networks", "transcriptomes", "microbiology", "Parasitology", "Zoology", "Infectious diseases", "Parasitic diseases", "Veterinary diseases", "Veterinary parasitology", "bovine", "lymphosarcoma", "infected", "exhibits", "irreversible", "reconfiguration"], "article_id"=>732179, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Jane H. Kinnaird", "William Weir", "Zeeshan Durrani", "Sreerekha S. Pillai", "Margaret Baird", "Brian R. Shiels"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0066833.s001", "https://dx.doi.org/10.1371/journal.pone.0066833.s002", "https://dx.doi.org/10.1371/journal.pone.0066833.s003", "https://dx.doi.org/10.1371/journal.pone.0066833.s004", "https://dx.doi.org/10.1371/journal.pone.0066833.s005", "https://dx.doi.org/10.1371/journal.pone.0066833.s006", "https://dx.doi.org/10.1371/journal.pone.0066833.s007", "https://dx.doi.org/10.1371/journal.pone.0066833.s008", "https://dx.doi.org/10.1371/journal.pone.0066833.s009", "https://dx.doi.org/10.1371/journal.pone.0066833.s010", "https://dx.doi.org/10.1371/journal.pone.0066833.s011"], "stats"=>{"downloads"=>57, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/A_Bovine_Lymphosarcoma_Cell_Line_Infected_with_Theileria_annulata_Exhibits_an_Irreversible_Reconfiguration_of_Host_Cell_Gene_Expression/732179", "title"=>"A Bovine Lymphosarcoma Cell Line Infected with <i>Theileria annulata</i> Exhibits an Irreversible Reconfiguration of Host Cell Gene Expression", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-06-26 08:45:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/1101906"], "description"=>"<p>Semi-quantitative RT-PCR carried out for a range of bovine genes to confirm the differential expressions determined from the microarray hybridisation and analysis of BL20 compared to TBL20 and for TBL20 following BW720c treatment. Actin or GAPDH were used as constitutively expressed reference genes and all genes tested showed similar profiles to hybridisation data from the array. The overall microarray profile is illustrated on the left of each panel; parasite infection (PI); buparvaquone (BW720c); elevated in TBL20 (▴); repressed in TBL20 (▾). BL20 and TBL20 without BW720c (−) and during BW720c treatment of TBL20 at 24 and 48 hour time points.</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome expression analysis", "Molecular genetics", "gene expression", "microarrays", "genetics", "Gene function", "Genome analysis tools", "Genetic networks", "transcriptomes", "microbiology", "Parasitology", "Zoology", "Infectious diseases", "Parasitic diseases", "Veterinary diseases", "Veterinary parasitology", "rt-pcr", "bovine", "genes", "confirms", "microarray"], "article_id"=>732161, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Jane H. Kinnaird", "William Weir", "Zeeshan Durrani", "Sreerekha S. Pillai", "Margaret Baird", "Brian R. Shiels"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066833.g004", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Semi_quantitative_RT_PCR_for_selected_bovine_genes_confirms_the_microarray_expression_data_/732161", "title"=>"Semi-quantitative RT-PCR for selected bovine genes confirms the microarray expression data.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-26 08:45:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/1101904"], "description"=>"<p>Profiles were derived from pairwise comparisons, BL20 vs TBL20; TBL20 vs TBL20_BW720c_24 h; TBL20_BW720c_24 h vs TBL20_BW720c_48 h as defined using RP with 5% FDR. The total number of differentially expressed genes in TBL20 compared to BL20 was 3,079. In addition to those genes exhibiting reversal in expression at 24 h, a further 303 (10%) showed reversal in the parasite induced expression profile at 48 h. We cannot distinguish whether these represent delayed reversal due to parasite death and hence associated with Group 2 or an apoptosis associated switch in expression of a gene that is non-responsive to parasite death (Group 3). Within Group 4, 30% showed enhancement in original parasite induced expression at 48 h only. Predominant trend in direction of expression in the group, solid line; alternative direction trend in the group, dashed line.</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome expression analysis", "Molecular genetics", "gene expression", "microarrays", "genetics", "Gene function", "Genome analysis tools", "Genetic networks", "transcriptomes", "microbiology", "Parasitology", "Zoology", "Infectious diseases", "Parasitic diseases", "Veterinary diseases", "Veterinary parasitology", "groups", "profiles", "bw720c"], "article_id"=>732159, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Jane H. Kinnaird", "William Weir", "Zeeshan Durrani", "Sreerekha S. Pillai", "Margaret Baird", "Brian R. Shiels"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066833.g003", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Main_groups_of_gene_expression_profiles_obtained_over_the_BW720c_time_course_/732159", "title"=>"Main groups of gene expression profiles obtained over the BW720c time course.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-26 08:45:05"}

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Relative Metric

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