Targeted Methylation of the Epithelial Cell Adhesion Molecule (EpCAM) Promoter to Silence Its Expression in Ovarian Cancer Cells
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{"title"=>"Targeted methylation of the Epithelial Cell Adhesion Molecule (EpCAM) promoter to silence its expression in ovarian cancer cells", "type"=>"journal", "authors"=>[{"first_name"=>"Suneetha", "last_name"=>"Nunna", "scopus_author_id"=>"55523919400"}, {"first_name"=>"Richard", "last_name"=>"Reinhardt", "scopus_author_id"=>"7101612726"}, {"first_name"=>"Sergey", "last_name"=>"Ragozin", "scopus_author_id"=>"26425237700"}, {"first_name"=>"Albert", "last_name"=>"Jeltsch", "scopus_author_id"=>"7005736654"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84900412888", "doi"=>"10.1371/journal.pone.0087703", "pui"=>"373070269", "issn"=>"19326203", "pmid"=>"24489952", "isbn"=>"10.1371/journal.pone.0087703", "scopus"=>"2-s2.0-84900412888"}, "id"=>"2f65cab7-8944-34f6-89b0-6aef22b712fb", "abstract"=>"The Epithelial Cell Adhesion Molecule (EpCAM) is overexpressed in many cancers including ovarian cancer and EpCAM overexpression correlates with decreased survival of patients. It was the aim of this study to achieve a targeted methylation of the EpCAM promoter and silence EpCAM gene expression using an engineered zinc finger protein that specifically binds the EpCAM promoter fused to the catalytic domain of the Dnmt3a DNA methyltransferase. We show that transient transfection of this construct increased the methylation of the EpCAM promoter in SKOV3 cells from 4-8% in untreated cells to 30%. Up to 48% methylation was observed in stable cell lines which express the chimeric methyltransferase. Control experiments confirmed that the methylation was dependent on the fusion of the Zinc finger and the methyltransferase domains and specific for the target region. The stable cell lines with methylated EpCAM promoter showed a 60-80% reduction of EpCAM expression as determined at mRNA and protein level and exhibited a significantly reduced cell proliferation. Our data indicate that targeted methylation of the EpCAM promoter could be an approach in the therapy of EpCAM overexpressing cancers.", "link"=>"http://www.mendeley.com/research/targeted-methylation-epithelial-cell-adhesion-molecule-epcam-promoter-silence-expression-ovarian-can", "reader_count"=>60, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>3, "Researcher"=>10, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>16, "Student > Postgraduate"=>4, "Student > Master"=>9, "Other"=>3, "Student > Bachelor"=>5, "Lecturer"=>2, "Professor"=>4}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>3, "Researcher"=>10, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>16, "Student > Postgraduate"=>4, "Student > Master"=>9, "Other"=>3, "Student > Bachelor"=>5, "Lecturer"=>2, "Professor"=>4}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>10, "Agricultural and Biological Sciences"=>39, "Medicine and Dentistry"=>1, "Philosophy"=>1, "Neuroscience"=>1, "Chemical Engineering"=>2, "Chemistry"=>3, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Neuroscience"=>{"Neuroscience"=>1}, "Chemistry"=>{"Chemistry"=>3}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>39}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>10}, "Unspecified"=>{"Unspecified"=>2}, "Chemical Engineering"=>{"Chemical Engineering"=>2}, "Philosophy"=>{"Philosophy"=>1}}, "reader_count_by_country"=>{"Colombia"=>1, "Canada"=>1, "Hong Kong"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1365694"], "description"=>"<p>The gene is shown in blue, its CpG island in green and the amplicon in black. The amplicon sequence is given below, the ZF binding site sequence is shaded in red. This picture was generated using University of California Santa Cruz genome browser (<a href=\"http://genome.ucsc.edu/\" target=\"_blank\">http://genome.ucsc.edu/</a>) <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0087703#pone.0087703-Kent1\" target=\"_blank\">[66]</a>.</p>", "links"=>[], "tags"=>["Biochemistry", "Nucleic acids", "dna", "DNA modification", "proteins", "DNA-binding proteins", "Regulatory proteins", "enzymes", "genetics", "epigenetics", "gene expression", "Non-clinical medicine", "epcam", "chromosome"], "article_id"=>917452, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Suneetha Nunna", "Richard Reinhardt", "Sergey Ragozin", "Albert Jeltsch"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087703.g002", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genome_context_of_the_EpCAM_gene_indicated_by_a_blue_bar_on_chromosome_2_p21_/917452", "title"=>"Genome context of the EpCAM gene (indicated by a blue bar) on chromosome 2 p21.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-29 03:06:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/1365704"], "description"=>"<p>A) Results of CCK8 cell proliferation assays conducted with the CD1 and CD2 stable cell lines and SKOV3 cells as reference. The results plotted are from four independent experiments and the error bars indicate the standard error of the mean. B) Viable cell counting performed by Trypan blue staining. The graph represents the data from two independent experiments and the error bars indicate the standard error of the mean.</p>", "links"=>[], "tags"=>["Biochemistry", "Nucleic acids", "dna", "DNA modification", "proteins", "DNA-binding proteins", "Regulatory proteins", "enzymes", "genetics", "epigenetics", "gene expression", "Non-clinical medicine", "epcam", "inhibits", "proliferation", "skov3"], "article_id"=>917461, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Suneetha Nunna", "Richard Reinhardt", "Sergey Ragozin", "Albert Jeltsch"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087703.g006", "stats"=>{"downloads"=>2, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Down_regulation_of_EpCAM_expression_inhibits_the_proliferation_of_SKOV3_cells_/917461", "title"=>"Down regulation of EpCAM expression inhibits the proliferation of SKOV3 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-29 03:06:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/1365703"], "description"=>"<p>A) Example of the RT qPCR analysis of EpCAM (left) and beta actin (right) mRNA amounts in SKOV3 cells and in two independent cell lines which stably express the ZF-Dnmt3a construct (CD1 and CD2). B) Quantification of the RT qPCR analysis of EpCAM expression as shown in panel A. We carried out two independent RNA preparations each analyzed in three technical repeats. The image shows the average of both results, the error bars indicate the standard error. C) Example of the Western blot analysis of EpCAM expression in SKOV3 cells and the CD1 and CD2 stable cell lines (upper panel). Beta actin was used as loading control (lower panel). The EpCAM and beta actin bands are marked with arrows. D) Quantification of the Western Blot analysis of EpCAM expression as shown in panel C. The figure shows an average of two independent experiments, the error bars indicate the standard deviation of the data.</p>", "links"=>[], "tags"=>["Biochemistry", "Nucleic acids", "dna", "DNA modification", "proteins", "DNA-binding proteins", "Regulatory proteins", "enzymes", "genetics", "epigenetics", "gene expression", "Non-clinical medicine", "epcam", "targeted", "promoter", "methylation"], "article_id"=>917460, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Suneetha Nunna", "Richard Reinhardt", "Sergey Ragozin", "Albert Jeltsch"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087703.g005", "stats"=>{"downloads"=>2, "page_views"=>24, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_EpCAM_gene_expression_after_targeted_promoter_methylation_in_stable_cell_lines_/917460", "title"=>"Analysis of EpCAM gene expression after targeted promoter methylation in stable cell lines.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-29 03:06:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/1365698"], "description"=>"<p>Methylation of four non-target genes was analyzed (KIAA0179, DSCR3, Sumo3 and WRB). Data presentation is as in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0087703#pone-0087703-g003\" target=\"_blank\">Fig. 3</a>. The sequences of the regions analyzed here are given in the Supplementary <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0087703#pone.0087703.s001\" target=\"_blank\">Information S1</a>.</p>", "links"=>[], "tags"=>["Biochemistry", "Nucleic acids", "dna", "DNA modification", "proteins", "DNA-binding proteins", "Regulatory proteins", "enzymes", "genetics", "epigenetics", "gene expression", "Non-clinical medicine", "off-target", "methylation", "skov3", "cells", "bisulfite"], "article_id"=>917456, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Suneetha Nunna", "Richard Reinhardt", "Sergey Ragozin", "Albert Jeltsch"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087703.g004", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Absence_of_off_target_methylation_in_SKOV3_cells_analyzed_by_bisulfite_sequencing_/917456", "title"=>"Absence of off-target methylation in SKOV3 cells analyzed by bisulfite sequencing.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-29 03:06:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/1365696"], "description"=>"<p>The following abbreviations were used: SKOV3 cells, untreated cells; ZF, SKOV3 cells transfected with Zinc finger construct, ZF-Dnmt3aCD, cells transfected with the Zinc finger Dnmt3a catalytic domain construct; VEC cntrl, cells transfected with empty vector; Dnmt3aCD, cells transfected with a Dnmt3aCD construct without Zinc finger; CD1, stable cell line expressing ZF-Dnmt3aCD 1; CD2, stable cell line expressing ZF-Dnmt3aCD 2. The horizontal rows indicate the CpGs in the amplicon analyzed and the vertical rows represent individual clones that were sequenced. The blue and red colors represent unmethylated CpG and methylated CpG, respectively, for white colored sites, the methylation state is unknown due to technical reasons.</p>", "links"=>[], "tags"=>["Biochemistry", "Nucleic acids", "dna", "DNA modification", "proteins", "DNA-binding proteins", "Regulatory proteins", "enzymes", "genetics", "epigenetics", "gene expression", "Non-clinical medicine", "methylation", "epcam", "promoter", "skov3"], "article_id"=>917454, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Suneetha Nunna", "Richard Reinhardt", "Sergey Ragozin", "Albert Jeltsch"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087703.g003", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Examples_of_the_results_of_the_DNA_methylation_analysis_of_the_EpCAM_gene_promoter_in_SKOV3_cells_/917454", "title"=>"Examples of the results of the DNA methylation analysis of the EpCAM gene promoter in SKOV3 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-29 03:06:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/1365693"], "description"=>"<p>The blue bar represents the ZF binding site, unfilled lollipops represent unmethylated CpGs and filled lollipops represent methylated CpGs.</p>", "links"=>[], "tags"=>["Biochemistry", "Nucleic acids", "dna", "DNA modification", "proteins", "DNA-binding proteins", "Regulatory proteins", "enzymes", "genetics", "epigenetics", "gene expression", "Non-clinical medicine", "targeted", "methylation", "zinc", "fingers", "fused", "catalytic", "methyltransferase", "dnmt3a"], "article_id"=>917451, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Suneetha Nunna", "Richard Reinhardt", "Sergey Ragozin", "Albert Jeltsch"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087703.g001", "stats"=>{"downloads"=>3, "page_views"=>87, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Principle_of_targeted_DNA_methylation_and_gene_silencing_using_Zinc_fingers_ZF_fused_to_the_catalytic_domain_of_the_DNA_methyltransferase_Dnmt3a_Dnmt3aCD_/917451", "title"=>"Principle of targeted DNA methylation and gene silencing using Zinc fingers (ZF) fused to the catalytic domain of the DNA methyltransferase Dnmt3a (Dnmt3aCD).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-29 03:06:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/1365705"], "description"=>"<div><p>The Epithelial Cell Adhesion Molecule (EpCAM) is overexpressed in many cancers including ovarian cancer and EpCAM overexpression correlates with decreased survival of patients. It was the aim of this study to achieve a targeted methylation of the EpCAM promoter and silence EpCAM gene expression using an engineered zinc finger protein that specifically binds the EpCAM promoter fused to the catalytic domain of the Dnmt3a DNA methyltransferase. We show that transient transfection of this construct increased the methylation of the EpCAM promoter in SKOV3 cells from 4–8% in untreated cells to 30%. Up to 48% methylation was observed in stable cell lines which express the chimeric methyltransferase. Control experiments confirmed that the methylation was dependent on the fusion of the Zinc finger and the methyltransferase domains and specific for the target region. The stable cell lines with methylated EpCAM promoter showed a 60–80% reduction of EpCAM expression as determined at mRNA and protein level and exhibited a significantly reduced cell proliferation. Our data indicate that targeted methylation of the EpCAM promoter could be an approach in the therapy of EpCAM overexpressing cancers.</p></div>", "links"=>[], "tags"=>["Biochemistry", "Nucleic acids", "dna", "DNA modification", "proteins", "DNA-binding proteins", "Regulatory proteins", "enzymes", "genetics", "epigenetics", "gene expression", "Non-clinical medicine", "methylation", "epithelial", "adhesion", "promoter", "ovarian", "cancer"], "article_id"=>917462, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Suneetha Nunna", "Richard Reinhardt", "Sergey Ragozin", "Albert Jeltsch"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087703", "stats"=>{"downloads"=>9, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Targeted_Methylation_of_the_Epithelial_Cell_Adhesion_Molecule_EpCAM_Promoter_to_Silence_Its_Expression_in_Ovarian_Cancer_Cells_/917462", "title"=>"Targeted Methylation of the Epithelial Cell Adhesion Molecule (EpCAM) Promoter to Silence Its Expression in Ovarian Cancer Cells", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-01-29 03:06:40"}

PMC Usage Stats | Further Information

  • {"unique-ip"=>"60", "full-text"=>"56", "pdf"=>"39", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"16", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"2"}
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  • {"unique-ip"=>"11", "full-text"=>"5", "pdf"=>"10", "abstract"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"12", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"6"}
  • {"unique-ip"=>"27", "full-text"=>"19", "pdf"=>"18", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"14", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2014", "month"=>"4"}
  • {"unique-ip"=>"19", "full-text"=>"20", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"4"}
  • {"unique-ip"=>"11", "full-text"=>"13", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"5"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"6"}
  • {"unique-ip"=>"11", "full-text"=>"11", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"7"}
  • {"unique-ip"=>"13", "full-text"=>"9", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"3"}
  • {"unique-ip"=>"13", "full-text"=>"13", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"2"}
  • {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
  • {"unique-ip"=>"18", "full-text"=>"18", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"9"}
  • {"unique-ip"=>"15", "full-text"=>"15", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"10"}
  • {"unique-ip"=>"16", "full-text"=>"17", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"7"}
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  • {"unique-ip"=>"20", "full-text"=>"18", "pdf"=>"11", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"10"}
  • {"unique-ip"=>"19", "full-text"=>"20", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"23", "full-text"=>"16", "pdf"=>"6", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2014", "month"=>"11"}
  • {"unique-ip"=>"12", "full-text"=>"10", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2014", "month"=>"12"}
  • {"unique-ip"=>"23", "full-text"=>"22", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"1"}
  • {"unique-ip"=>"25", "full-text"=>"19", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"11"}
  • {"unique-ip"=>"13", "full-text"=>"9", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
  • {"unique-ip"=>"19", "full-text"=>"9", "pdf"=>"15", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
  • {"unique-ip"=>"18", "full-text"=>"17", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"10", "full-text"=>"8", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"9", "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"=>"7"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"11", "full-text"=>"11", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"14", "full-text"=>"15", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"6", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
  • {"unique-ip"=>"9", "full-text"=>"5", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"9", "full-text"=>"11", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"8", "full-text"=>"16", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"6", "full-text"=>"9", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"14", "full-text"=>"16", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"12", "full-text"=>"11", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"6", "full-text"=>"24", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
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  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
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  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
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Relative Metric

{"start_date"=>"2014-01-01T00:00:00Z", "end_date"=>"2014-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[291]}, {"subject_area"=>"/Biology and life sciences/Biochemistry", "average_usage"=>[282]}, {"subject_area"=>"/Biology and life sciences/Cell biology", "average_usage"=>[286]}, {"subject_area"=>"/Biology and life sciences/Genetics", "average_usage"=>[306, 482]}, {"subject_area"=>"/Biology and life sciences/Molecular biology", "average_usage"=>[292, 461]}, {"subject_area"=>"/Medicine and health sciences", "average_usage"=>[285]}, {"subject_area"=>"/Medicine and health sciences/Oncology", "average_usage"=>[266]}]}
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