Aging Mice Show a Decreasing Correlation of Gene Expression within Genetic Modules
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{"title"=>"Aging mice show a decreasing correlation of gene expression within genetic modules", "type"=>"journal", "authors"=>[{"first_name"=>"Lucinda K.", "last_name"=>"Southworth", "scopus_author_id"=>"23490335400"}, {"first_name"=>"Art B.", "last_name"=>"Owen", "scopus_author_id"=>"7202050285"}, {"first_name"=>"Stuart K.", "last_name"=>"Kim", "scopus_author_id"=>"8073488900"}], "year"=>2009, "source"=>"PLoS Genetics", "identifiers"=>{"pui"=>"358116873", "sgr"=>"74249118093", "pmid"=>"20019809", "scopus"=>"2-s2.0-74249118093", "isbn"=>"1553-7404 (Electronic)\\r1553-7390 (Linking)", "doi"=>"10.1371/journal.pgen.1000776", "issn"=>"15537390"}, "id"=>"6afb20b7-ee50-3685-b5bb-5effbbaf7812", "abstract"=>"<title>Author Summary</title> <p>There is mounting evidence that mammalian aging is marked by increased gene transcriptional variation. This trend was shown not only by studying gene expression in single cells (Bahar et al. 2006), but at the coarse tissue resolution as well (Somel et al. 2006; Li et al. 2009). These led us to believe that looking at absolute changes in expression level alone may not tell the whole story of transcriptional changes in age. Instead the story may be in the more subtle changes in the coordination of expression among multiple genes. For this reason, we decided to look at changes in co-expression relationships with age. To this end, we developed a methodology for differential co-expression network analysis for the comparison gene co-expression on a global scale. We applied this methodology to compare co-expression between young (16-month) and old (24-month) mice. This allowed us to find both gene groups whose coordination appear to be affected by age and to propose potential mechanisms for the change. We believe our work is of broad importance because it represents a different paradigm for looking not only at aging but also at any complex condition or disease—away from changes in individual genes towards changes in gene relationships.</p>", "link"=>"http://www.mendeley.com/research/aging-mice-show-decreasing-correlation-gene-expression-within-genetic-modules", "reader_count"=>146, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>16, "Researcher"=>38, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>48, "Student > Postgraduate"=>6, "Student > Master"=>13, "Other"=>3, "Student > Bachelor"=>7, "Lecturer"=>4, "Lecturer > Senior Lecturer"=>1, "Professor"=>4}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>16, "Researcher"=>38, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>48, "Student > Postgraduate"=>6, "Student > Master"=>13, "Other"=>3, "Student > Bachelor"=>7, "Lecturer"=>4, "Lecturer > Senior Lecturer"=>1, "Professor"=>4}, "reader_count_by_subject_area"=>{"Unspecified"=>5, "Engineering"=>2, "Biochemistry, Genetics and Molecular Biology"=>16, "Mathematics"=>6, "Agricultural and Biological Sciences"=>90, "Medicine and Dentistry"=>9, "Neuroscience"=>4, "Physics and Astronomy"=>2, "Chemical Engineering"=>1, "Computer Science"=>6, "Immunology and Microbiology"=>4, "Economics, Econometrics and Finance"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>9}, "Neuroscience"=>{"Neuroscience"=>4}, "Physics and Astronomy"=>{"Physics and Astronomy"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>4}, "Economics, Econometrics and Finance"=>{"Economics, Econometrics and Finance"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>90}, "Computer Science"=>{"Computer Science"=>6}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>16}, "Mathematics"=>{"Mathematics"=>6}, "Unspecified"=>{"Unspecified"=>5}, "Chemical Engineering"=>{"Chemical Engineering"=>1}}, "reader_count_by_country"=>{"United States"=>9, "Japan"=>2, "United Kingdom"=>4, "Portugal"=>1, "Switzerland"=>1, "India"=>1, "Greece"=>1, "Canada"=>1, "Netherlands"=>2, "South Korea"=>1, "Ireland"=>1, "Finland"=>1, "Brazil"=>2, "Germany"=>3}, "group_count"=>2}

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  • {"files"=>["https://ndownloader.figshare.com/files/432339", "https://ndownloader.figshare.com/files/432350", "https://ndownloader.figshare.com/files/432372", "https://ndownloader.figshare.com/files/432382", "https://ndownloader.figshare.com/files/432389", "https://ndownloader.figshare.com/files/432404"], "description"=>"<div><p>In this work we present a method for the differential analysis of gene co-expression networks and apply this method to look for large-scale transcriptional changes in aging. We derived synonymous gene co-expression networks from AGEMAP expression data for 16-month-old and 24-month-old mice. We identified a number of functional gene groups that change co-expression with age. Among these changing groups we found a trend towards declining correlation with age. In particular, we identified a modular (as opposed to uniform) decline in general correlation with age. We identified potential transcriptional mechanisms that may aid in modular correlation decline. We found that computationally identified targets of the NF-<em>Κ</em>B transcription factor decrease expression correlation with age. Finally, we found that genes that are prone to declining co-expression tend to be co-located on the chromosome. Our results conclude that there is a modular decline in co-expression with age in mice. They also indicate that factors relating to both chromosome domains and specific transcription factors may contribute to the decline.</p></div>", "links"=>[], "tags"=>["aging", "mice", "decreasing", "modules"], "article_id"=>145312, "categories"=>["Genetics", "Medicine"], "users"=>["Lucinda K. Southworth", "Art B. Owen", "Stuart K. Kim"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1000776.s001", "https://dx.doi.org/10.1371/journal.pgen.1000776.s002", "https://dx.doi.org/10.1371/journal.pgen.1000776.s003", "https://dx.doi.org/10.1371/journal.pgen.1000776.s004", "https://dx.doi.org/10.1371/journal.pgen.1000776.s005", "https://dx.doi.org/10.1371/journal.pgen.1000776.s006"], "stats"=>{"downloads"=>21, "page_views"=>36, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Aging_Mice_Show_a_Decreasing_Correlation_of_Gene_Expression_within_Genetic_Modules/145312", "title"=>"Aging Mice Show a Decreasing Correlation of Gene Expression within Genetic Modules", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2009-12-18 01:28:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/871104"], "description"=>"<p>(A) The number of co-expression- and Gene Ontology (GO)- defined groups that change with age. The red bars indicate decreasing co-expression, and the blue bars indicate increasing co-expression. The dotted line represents the number of groups expected under the null distribution. (B) Histogram of the sum of the edge weights for the clusters using and . Again the red bars indicate decreasing co-expression, and the blue bars indicate increasing co-expression. Top left panel: The total number of groups that decrease in co-expression exceeds any of the permuted values. Top right panel: The total number of groups that decrease in co-expression exceeds all but 4/1,000 of the permuted values.</p>", "links"=>[], "tags"=>["clusters"], "article_id"=>541568, "categories"=>["Genetics", "Medicine"], "users"=>["Lucinda K. Southworth", "Art B. Owen", "Stuart K. Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000776.g002", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Functional_gene_clusters_tend_to_decrease_with_age_/541568", "title"=>"Functional gene clusters tend to decrease with age.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-12-18 00:26:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/871533"], "description"=>"a<p>The percentile is calculated as the percent of permutation that exceeds the true correlation difference. The percentile corresponds to 100×[one-tailed p-value. Gene groups marked with a * indicate that the correlation is increasing with age.</p>b<p>If a co-expression cluster is enriched for genes in a GO category, genes in a KEGG category, or genes that share a protein motif from the Interpro (IPR) database, then the associated category is listed <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000776#pgen.1000776-Ogata1\" target=\"_blank\">[48]</a>,<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000776#pgen.1000776-Apweiler1\" target=\"_blank\">[49]</a>.</p>c<p>The <i>p</i>-value for enrichment is calculated using the hypergeometric distribution (see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000776#s4\" target=\"_blank\">Materials and Methods</a>).</p>", "links"=>[], "tags"=>["clusters", "ontology", "categories"], "article_id"=>541991, "categories"=>["Genetics", "Medicine"], "users"=>["Lucinda K. Southworth", "Art B. Owen", "Stuart K. Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000776.t001", "stats"=>{"downloads"=>3, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Co_expression_clusters_and_Gene_Ontology_GO_categories_that_change_correlation_with_age_at_the_top_1_percentile_/541991", "title"=>"Co-expression clusters and Gene Ontology (GO) categories that change correlation with age at the top 1 percentile.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-12-18 00:33:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/871051"], "description"=>"<p>(A) Collections of microarrays can be used to look for differences in co-expression networks with age. (B) Each edge in the difference network represents the change in correlation that occurs between young and old mice. The edge weights in the 16-month and the 24-month networks are a function of the correlation in expression between two genes. The edge weights in the difference network represent the magnitude of the difference in correlations. The correlation difference matrix view is a heat map representation of the difference network. In both the network view and the matrix view, red represents a decrease in correlation, and blue represents an increase.</p>", "links"=>[], "tags"=>["differential", "co-expression"], "article_id"=>541506, "categories"=>["Genetics", "Medicine"], "users"=>["Lucinda K. Southworth", "Art B. Owen", "Stuart K. Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000776.g001", "stats"=>{"downloads"=>3, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_novel_approach_for_differential_co_expression_network_analysis_/541506", "title"=>"A novel approach for differential co-expression network analysis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-12-18 00:25:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/871584"], "description"=>"a<p>Only clusters significantly enriched for a Gene Ontology (GO) category are listed.</p>b<p>The GO category with the highest enrichment in the gene group.</p>c<p>The <i>p</i>-value for enrichment is calculated using the hypergeometric distribution.</p>", "links"=>[], "tags"=>["genes", "defined"], "article_id"=>542051, "categories"=>["Genetics", "Medicine"], "users"=>["Lucinda K. Southworth", "Art B. Owen", "Stuart K. Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000776.t002", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Groups_of_genes_defined_using_the_cluster_distance_/542051", "title"=>"Groups of genes defined using the cluster distance .", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-12-18 00:34:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/871295"], "description"=>"<p>(A) The clustering coefficient () versus the connectivity () after simulation of uniform co-expression loss. Each dot represents a probe in either the 16-month-old (<i>blue</i>) and 24-month-old (<i>red</i>) networks. All of the probes with at least one neighbor are plotted. The gray lines represent the 100 node-deletion simulations. (B) The clustering coefficient () versus the connectivity () for young and old mice as contrasted with the cluster-based deletion simulation. Each dot represents a probe in either the 16-month-old (<i>blue</i>) and 24-month-old (<i>red</i>) networks. All of the probes with at least one neighbor are plotted. The distributions from the cluster-based deletion simulations are shown in gray.</p>", "links"=>[], "tags"=>["simulations", "modular", "co-expression"], "article_id"=>541762, "categories"=>["Genetics", "Medicine"], "users"=>["Lucinda K. Southworth", "Art B. Owen", "Stuart K. Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000776.g004", "stats"=>{"downloads"=>3, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Deletion_simulations_indicate_modular_co_expression_loss_/541762", "title"=>"Deletion simulations indicate modular co-expression loss.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-12-18 00:29:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/871506"], "description"=>"a<p> is the number of downstream targets.</p>b<p>The percentile is calculated as the percent of permutation that exceeds the true correlation difference and corresponds to 100×[one-tailed p-value.</p>", "links"=>[], "tags"=>["groups"], "article_id"=>541963, "categories"=>["Genetics", "Medicine"], "users"=>["Lucinda K. Southworth", "Art B. Owen", "Stuart K. Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000776.t004", "stats"=>{"downloads"=>2, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Transfac_defined_gene_groups_that_change_correlation_with_age_in_the_top_1_percentile_/541963", "title"=>"Transfac-defined gene groups that change correlation with age in the top 1 percentile.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-12-18 00:32:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/871453"], "description"=>"<p>(A) For a window of a set size, genes with connectivity in the difference network above a threshold are counted. (B) The positions of genes are plotted on the chromosome. The black bars are genes that do not meet the loss score threshold. Genes with a high loss score (<i>red bars</i>) were found to be clustered together.</p>", "links"=>[], "tags"=>["prone", "clustered"], "article_id"=>541913, "categories"=>["Genetics", "Medicine"], "users"=>["Lucinda K. Southworth", "Art B. Owen", "Stuart K. Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000776.g006", "stats"=>{"downloads"=>6, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genes_that_are_prone_to_correlation_loss_are_clustered_on_the_chromosome_/541913", "title"=>"Genes that are prone to correlation loss are clustered on the chromosome.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-12-18 00:31:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/871371"], "description"=>"<p>Red represents a decrease in correlation between two genes, and blue represents an increase. The yellow boxes identify the subsets of genes that are strongly decorrelated.</p>", "links"=>[], "tags"=>["changes", "targets", "transcription", "factors"], "article_id"=>541829, "categories"=>["Genetics", "Medicine"], "users"=>["Lucinda K. Southworth", "Art B. Owen", "Stuart K. Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000776.g005", "stats"=>{"downloads"=>3, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Heat_map_representation_of_correlation_changes_in_targets_of_transcription_factors_that_significantly_decrease_correlation_with_age_/541829", "title"=>"Heat map representation of correlation changes in targets of transcription factors that significantly decrease correlation with age.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-12-18 00:30:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/871560"], "description"=>"a<p>Only clusters significantly enriched for a Gene Ontology (GO) category are listed.</p>b<p>The GO category with the highest enrichment in the gene group.</p>c<p>The <i>p</i>-value for enrichment is calculated using the hypergeometric distribution.</p>", "links"=>[], "tags"=>["genes", "defined"], "article_id"=>542021, "categories"=>["Genetics", "Medicine"], "users"=>["Lucinda K. Southworth", "Art B. Owen", "Stuart K. Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000776.t003", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Groups_of_genes_defined_using_the_cluster_distance_/542021", "title"=>"Groups of genes defined using the cluster distance .", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-12-18 00:33:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/871205"], "description"=>"<p>Each dot represents a probe in either the 16-month-old (<i>blue</i>) and 24-month-old (<i>red</i>) networks. All of the probes with at least one neighbor are plotted.</p>", "links"=>[], "tags"=>["clustering", "coefficient", "connectivity", "distributions"], "article_id"=>541665, "categories"=>["Genetics", "Medicine"], "users"=>["Lucinda K. Southworth", "Art B. Owen", "Stuart K. Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000776.g003", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Difference_in_the_clustering_coefficient_versus_the_connectivity_distributions_between_young_and_old_networks_/541665", "title"=>"Difference in the clustering coefficient () versus the connectivity () distributions between young and old networks.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-12-18 00:27:45"}

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Relative Metric

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