Modeling Co-Expression across Species for Complex Traits: Insights to the Difference of Human and Mouse Embryonic Stem Cells
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{"title"=>"Modeling co-expression across species for complex traits: Insights to the difference of human and mouse embryonic stem cells", "type"=>"journal", "authors"=>[{"first_name"=>"Jun", "last_name"=>"Cai", "scopus_author_id"=>"57094424100"}, {"first_name"=>"Dan", "last_name"=>"Xie", "scopus_author_id"=>"47761571200"}, {"first_name"=>"Zhewen", "last_name"=>"Fan", "scopus_author_id"=>"56301906700"}, {"first_name"=>"Hiram", "last_name"=>"Chipperfield", "scopus_author_id"=>"6505930002"}, {"first_name"=>"John", "last_name"=>"Marden", "scopus_author_id"=>"7004287772"}, {"first_name"=>"Wing H.", "last_name"=>"Wong", "scopus_author_id"=>"7403972659"}, {"first_name"=>"Sheng", "last_name"=>"Zhong", "scopus_author_id"=>"55682668900"}], "year"=>2010, "source"=>"PLoS Computational Biology", "identifiers"=>{"issn"=>"1553734X", "scopus"=>"2-s2.0-77950847851", "pui"=>"358620660", "doi"=>"10.1371/journal.pcbi.1000707", "isbn"=>"1553-7358 (Electronic)\\r1553-734X (Linking)", "sgr"=>"77950847851", "pmid"=>"20300647"}, "id"=>"871ce28a-a4f6-3a69-9783-2145d4d25706", "abstract"=>"Complex interactions between genes or proteins contribute substantially to phenotypic evolution. We present a probabilistic model and a maximum likelihood approach for cross-species clustering analysis and for identification of conserved as well as species-specific co-expression modules. This model enables a \"soft\" cross-species clustering (SCSC) approach by encouraging but not enforcing orthologous genes to be grouped into the same cluster. SCSC is therefore robust to obscure orthologous relationships and can reflect different functional roles of orthologous genes in different species. We generated a time-course gene expression dataset for differentiating mouse embryonic stem (ES) cells, and compiled a dataset of published gene expression data on differentiating human ES cells. Applying SCSC to analyze these datasets, we identified conserved and species-specific gene regulatory modules. Together with protein-DNA binding data, an SCSC cluster specifically induced in murine ES cells indicated that the KLF2/4/5 transcription factors, although critical to maintaining the pluripotent phenotype in mouse ES cells, were decoupled from the OCT4/SOX2/NANOG regulatory module in human ES cells. Two of the target genes of murine KLF2/4/5, LIN28 and NODAL, were rewired to be targets of OCT4/SOX2/NANOG in human ES cells. Moreover, by mapping SCSC clusters onto KEGG signaling pathways, we identified the signal transduction components that were induced in pluripotent ES cells in either a conserved or a species-specific manner. These results suggest that the pluripotent cell identity can be established and maintained through more than one gene regulatory network.", "link"=>"http://www.mendeley.com/research/modeling-coexpression-across-species-complex-traits-insights-difference-human-mouse-embryonic-stem-c-3", "reader_count"=>25, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>5, "Researcher"=>10, "Student > Ph. D. Student"=>7, "Student > Master"=>1, "Other"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>5, "Researcher"=>10, "Student > Ph. D. Student"=>7, "Student > Master"=>1, "Other"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>6, "Agricultural and Biological Sciences"=>17, "Computer Science"=>2}, "reader_count_by_subdiscipline"=>{"Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>17}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>6}}, "reader_count_by_country"=>{"United States"=>4, "Brazil"=>1, "Germany"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/858292"], "description"=>"<p>The gene induced in either hES or mES cells, i.e., Clusters (2, *), (3, *) and (*, 3), are mapped onto all the signaling pathways documented in the KEGG database <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000707#pcbi.1000707-GolanMashiach1\" target=\"_blank\">[33]</a> and plotted using Cytoscape software (<a href=\"http://www.cytoscape.org\" target=\"_blank\">www.cytoscape.org</a>). Gray, blue and green nodes represent genes that are induced in hES cells only, mES cells only or both (conserved), respectively. The edges between any two nodes represent known protein-protein interactions documented in Cytoscape.</p>", "links"=>[], "tags"=>["components", "signaling", "pathways", "hes", "mes"], "article_id"=>528743, "categories"=>["Infectious Diseases", "Cell Biology", "Genetics", "Computational Biology"], "users"=>["Jun Cai", "Dan Xie", "Zhewen Fan", "Hiram Chipperfield", "John Marden", "Wing H. Wong", "Sheng Zhong"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000707.g003", "stats"=>{"downloads"=>3, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Induced_components_of_signaling_pathways_in_hES_and_mES_cells_/528743", "title"=>"Induced components of signaling pathways in hES and mES cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-12 02:25:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/858367"], "description"=>"<p>Nodes represent upregulated genes in ES cells in a conserved (blue, upregulated in both hES and mES cells) or species-specific (red, upregulated in mES cells only) manner. Edges represent positive regulatory relationships (activation) that are validated by ChIP-chip and RNAi data in both species (dark blue), in mouse only (red), or in human only (light blue). As the KLF module appears to have lost its regulatory function in hES cells, its target genes <i>ESRRB</i>, <i>FOXD3</i> and <i>SOCS3</i> have consistently lost their upregulation in hES cells as well (A). However, <i>LIN28</i> and <i>NODAL</i>, which are upregulated by the KLF module in mES cells, remain upregulated in hES cells. Their upregulation in hES cells might be activated by NANOG and OCT4 instead (B).</p>", "links"=>[], "tags"=>["klf"], "article_id"=>528821, "categories"=>["Infectious Diseases", "Cell Biology", "Genetics", "Computational Biology"], "users"=>["Jun Cai", "Dan Xie", "Zhewen Fan", "Hiram Chipperfield", "John Marden", "Wing H. Wong", "Sheng Zhong"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000707.g004", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Rewiring_of_the_KLF_regulatory_module_/528821", "title"=>"Rewiring of the KLF regulatory module.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-12 02:27:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/858118"], "description"=>"<p>1. G1–G8 are eight genes in Species 1, which have orthologues G1′–G8′ in Species 2. 2. G4 and G9′ do not have orthologues, but they participate in the clustering analysis. 3. The shapes of the lines represent gene expression patterns. For example, G1 has an increasing pattern and G6′ has a first decreasing and then increasing pattern. 4. The genes with the same color, except for the black color, are clustered together. Genes in black are “scattered” genes, which form a singleton cluster each.</p>", "links"=>[], "tags"=>["assumptions", "scsc"], "article_id"=>528572, "categories"=>["Infectious Diseases", "Cell Biology", "Genetics", "Computational Biology"], "users"=>["Jun Cai", "Dan Xie", "Zhewen Fan", "Hiram Chipperfield", "John Marden", "Wing H. Wong", "Sheng Zhong"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000707.g001", "stats"=>{"downloads"=>3, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Major_features_and_assumptions_of_the_SCSC_method_/528572", "title"=>"Major features and assumptions of the SCSC method.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-12 02:22:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/858180"], "description"=>"<p>Representative transcription regulators are listed in each cluster. Thick lines enclose clusters with upregulation in either mouse or human ES cells. Dotted lines enclose the conserved clusters with upregulation in ES cells of both species. Detailed expression patterns of every cluster and sample information are given in <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000707#pcbi.1000707.s006\" target=\"_blank\">Figure S2</a>.</p>", "links"=>[], "tags"=>["clusters", "mes", "hes", "differentiation"], "article_id"=>528633, "categories"=>["Infectious Diseases", "Cell Biology", "Genetics", "Computational Biology"], "users"=>["Jun Cai", "Dan Xie", "Zhewen Fan", "Hiram Chipperfield", "John Marden", "Wing H. Wong", "Sheng Zhong"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000707.g002", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_SCSC_clusters_of_mES_and_hES_cell_differentiation_data_/528633", "title"=>"SCSC clusters of mES and hES cell differentiation data.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-12 02:23:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/858419"], "description"=>"<p>Genes in the same family are embraced with the same parenthesis. Genes with a * are involved in the multiple pathways. Genes with <sup>&</sup> signs are transcriptional repressors or co-repressors. Genes with a <sup>#</sup> have abundant transcripts in mES cells, but they do not show obvious up or down regulation during differentiation of mES cells.</p>", "links"=>[], "tags"=>["genes", "participating", "signaling", "pathways", "es"], "article_id"=>528869, "categories"=>["Infectious Diseases", "Cell Biology", "Genetics", "Computational Biology"], "users"=>["Jun Cai", "Dan Xie", "Zhewen Fan", "Hiram Chipperfield", "John Marden", "Wing H. Wong", "Sheng Zhong"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000707.t001", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Distribution_of_genes_participating_in_six_signaling_pathways_in_the_ES_clusters_/528869", "title"=>"Distribution of genes participating in six signaling pathways in the ES clusters.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-03-12 02:27:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/426784", "https://ndownloader.figshare.com/files/426795", "https://ndownloader.figshare.com/files/426808", "https://ndownloader.figshare.com/files/426814", "https://ndownloader.figshare.com/files/426823", "https://ndownloader.figshare.com/files/426835", "https://ndownloader.figshare.com/files/426842", "https://ndownloader.figshare.com/files/426851", "https://ndownloader.figshare.com/files/426857", "https://ndownloader.figshare.com/files/426868", "https://ndownloader.figshare.com/files/426877", "https://ndownloader.figshare.com/files/426886"], "description"=>"<div><p>Complex interactions between genes or proteins contribute substantially to phenotypic evolution. We present a probabilistic model and a maximum likelihood approach for cross-species clustering analysis and for identification of conserved as well as species-specific co-expression modules. This model enables a “soft” cross-species clustering (SCSC) approach by encouraging but not enforcing orthologous genes to be grouped into the same cluster. SCSC is therefore robust to obscure orthologous relationships and can reflect different functional roles of orthologous genes in different species. We generated a time-course gene expression dataset for differentiating mouse embryonic stem (ES) cells, and compiled a dataset of published gene expression data on differentiating human ES cells. Applying SCSC to analyze these datasets, we identified conserved and species-specific gene regulatory modules. Together with protein-DNA binding data, an SCSC cluster specifically induced in murine ES cells indicated that the KLF2/4/5 transcription factors, although critical to maintaining the pluripotent phenotype in mouse ES cells, were decoupled from the OCT4/SOX2/NANOG regulatory module in human ES cells. Two of the target genes of murine KLF2/4/5, <em>LIN28</em> and <em>NODAL</em>, were rewired to be targets of OCT4/SOX2/NANOG in human ES cells. Moreover, by mapping SCSC clusters onto KEGG signaling pathways, we identified the signal transduction components that were induced in pluripotent ES cells in either a conserved or a species-specific manner. These results suggest that the pluripotent cell identity can be established and maintained through more than one gene regulatory network.</p></div>", "links"=>[], "tags"=>["modeling", "co-expression", "insights", "embryonic", "cells"], "article_id"=>144242, "categories"=>["Cancer", "Cell Biology", "Genetics", "Biological Sciences"], "users"=>["Jun Cai", "Dan Xie", "Zhewen Fan", "Hiram Chipperfield", "John Marden", "Wing H. Wong", "Sheng Zhong"], "doi"=>["https://dx.doi.org/10.1371/journal.pcbi.1000707.s001", "https://dx.doi.org/10.1371/journal.pcbi.1000707.s002", "https://dx.doi.org/10.1371/journal.pcbi.1000707.s003", "https://dx.doi.org/10.1371/journal.pcbi.1000707.s004", "https://dx.doi.org/10.1371/journal.pcbi.1000707.s005", "https://dx.doi.org/10.1371/journal.pcbi.1000707.s006", "https://dx.doi.org/10.1371/journal.pcbi.1000707.s007", "https://dx.doi.org/10.1371/journal.pcbi.1000707.s008", "https://dx.doi.org/10.1371/journal.pcbi.1000707.s009", "https://dx.doi.org/10.1371/journal.pcbi.1000707.s010", "https://dx.doi.org/10.1371/journal.pcbi.1000707.s011", "https://dx.doi.org/10.1371/journal.pcbi.1000707.s012"], "stats"=>{"downloads"=>35, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Modeling_Co_Expression_across_Species_for_Complex_Traits_Insights_to_the_Difference_of_Human_and_Mouse_Embryonic_Stem_Cells/144242", "title"=>"Modeling Co-Expression across Species for Complex Traits: Insights to the Difference of Human and Mouse Embryonic Stem Cells", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2010-03-12 01:10:42"}

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