Biomolecular Events in Cancer Revealed by Attractor Metagenes
Publication Date
February 21, 2013
Journal
PLOS Computational Biology
Authors
Wei Yi Cheng, Tai Hsien Ou Yang & Dimitris Anastassiou
Volume
9
Issue
2
Pages
e1002920
DOI
https://dx.plos.org/10.1371/journal.pcbi.1002920
Publisher URL
http://journals.plos.org/ploscompbiol/article?id=10.1371%2Fjournal.pcbi.1002920
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/23468608
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581797
Europe PMC
http://europepmc.org/abstract/MED/23468608
Web of Science
000315708600028
Scopus
84874763866
Mendeley
http://www.mendeley.com/research/biomolecular-events-cancer-revealed-attractor-metagenes-1
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Mendeley | Further Information

{"title"=>"Biomolecular Events in Cancer Revealed by Attractor Metagenes", "type"=>"journal", "authors"=>[{"first_name"=>"Wei Yi", "last_name"=>"Cheng", "scopus_author_id"=>"55105397700"}, {"first_name"=>"Tai Hsien Ou", "last_name"=>"Yang", "scopus_author_id"=>"51161763500"}, {"first_name"=>"Dimitris", "last_name"=>"Anastassiou", "scopus_author_id"=>"7006072162"}], "year"=>2013, "source"=>"PLoS Computational Biology", "identifiers"=>{"scopus"=>"2-s2.0-84874763866", "sgr"=>"84874763866", "issn"=>"1553734X", "arxiv"=>"1204.6538", "doi"=>"10.1371/journal.pcbi.1002920", "pmid"=>"23468608", "isbn"=>"1553-734X\\r1553-7358", "pui"=>"368490513"}, "id"=>"b0e6329e-ea71-332b-a2e4-96de57b37721", "abstract"=>"Mining gene expression profiles has proven valuable for identifying signatures serving as surrogates of cancer phenotypes. However, the similarities of such signatures across different cancer types have not been strong enough to conclude that they represent a universal biological mechanism shared among multiple cancer types. Here we present a computational method for generating signatures using an iterative process that converges to one of several precise attractors defining signatures representing biomolecular events, such as cell transdifferentiation or the presence of an amplicon. By analyzing rich gene expression datasets from different cancer types, we identified several such biomolecular events, some of which are universally present in all tested cancer types in nearly identical form. Although the method is unsupervised, we show that it often leads to attractors with strong phenotypic associations. We present several such multi-cancer attractors, focusing on three that are prominent and sharply defined in all cases: a mesenchymal transition attractor strongly associated with tumor stage, a mitotic chromosomal instability attractor strongly associated with tumor grade, and a lymphocyte-specific attractor.", "link"=>"http://www.mendeley.com/research/biomolecular-events-cancer-revealed-attractor-metagenes-1", "reader_count"=>110, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>9, "Researcher"=>39, "Student > Doctoral Student"=>6, "Student > Ph. D. Student"=>35, "Student > Postgraduate"=>2, "Student > Master"=>7, "Other"=>2, "Student > Bachelor"=>6, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>9, "Researcher"=>39, "Student > Doctoral Student"=>6, "Student > Ph. D. Student"=>35, "Student > Postgraduate"=>2, "Student > Master"=>7, "Other"=>2, "Student > Bachelor"=>6, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Engineering"=>8, "Biochemistry, Genetics and Molecular Biology"=>10, "Mathematics"=>3, "Agricultural and Biological Sciences"=>52, "Medicine and Dentistry"=>13, "Neuroscience"=>1, "Physics and Astronomy"=>2, "Chemistry"=>1, "Computer Science"=>16}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>8}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>13}, "Neuroscience"=>{"Neuroscience"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>52}, "Computer Science"=>{"Computer Science"=>16}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>10}, "Mathematics"=>{"Mathematics"=>3}, "Unspecified"=>{"Unspecified"=>4}}, "reader_count_by_country"=>{"Canada"=>1, "Sweden"=>1, "United States"=>7, "Japan"=>1, "Ukraine"=>1, "Poland"=>1, "Denmark"=>1, "United Kingdom"=>2, "Malaysia"=>1, "Australia"=>1, "Germany"=>1, "Spain"=>1}, "group_count"=>7}

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Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1005187"], "description"=>"<p>The 47 underlined genes are also among the top 100 genes of the mitotic CIN attractor (<a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002920#pcbi-1002920-t002\" target=\"_blank\">Table 2</a>).</p>", "links"=>[], "tags"=>["top-ranked", "genes", "concordance", "metabric", "dataset", "demonstrating", "enrichment", "mitotic", "cin"], "article_id"=>665805, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Wei-Yi Cheng", "Tai-Hsien Ou Yang", "Dimitris Anastassiou"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1002920.t004", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_List_of_top_ranked_genes_in_terms_of_survival_concordance_index_of_the_METABRIC_discovery_dataset_demonstrating_enrichment_of_the_mitotic_CIN_attractor_/665805", "title"=>"List of top-ranked genes in terms of survival concordance index of the METABRIC discovery dataset demonstrating enrichment of the mitotic CIN attractor.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 01:36:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/965676"], "description"=>"<p>The two metagenes were defined to be “consensus attractors” after ranking individual genes in terms of their average mutual information with the corresponding attractor metagenes, across all datasets, and selecting the genes having average mutual information greater than 0.5. These criteria led to 59 genes in the consensus mitotic CIN attractor (the top 59 genes in <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002920#pcbi-1002920-t002\" target=\"_blank\">Table 2</a>), and <i>AGR3, ESR1</i>, <i>CA12</i>, <i>AGR2</i>, <i>GATA3</i>, <i>FOXA1</i>, <i>MLPH</i> and <i>TBC1D9</i> (the top eight genes in <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002920#pcbi-1002920-t006\" target=\"_blank\">Table 6</a>) in the consensus estrogen receptor breast cancer attractor. These scatter plots reveal that ER-negative breast tumors have high mitotic chromosomal instability, but not necessarily vice versa.</p>", "links"=>[], "tags"=>["demonstrating", "mitotic", "cin", "attractor", "estrogen", "receptor"], "article_id"=>635373, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Wei-Yi Cheng", "Tai-Hsien Ou Yang", "Dimitris Anastassiou"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1002920.g005", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Scatter_plots_demonstrating_the_relationship_between_mitotic_CIN_attractor_and_estrogen_receptor_attractor_in_breast_cancer_/635373", "title"=>"Scatter plots demonstrating the relationship between mitotic CIN attractor and estrogen receptor attractor in breast cancer.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 11:33:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/1005146"], "description"=>"<p>Top 100 genes of the mitotic CIN attractor based on six datasets.</p>", "links"=>[], "tags"=>["100", "genes", "mitotic", "cin", "attractor"], "article_id"=>665768, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Wei-Yi Cheng", "Tai-Hsien Ou Yang", "Dimitris Anastassiou"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1002920.t002", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Top_100_genes_of_the_mitotic_CIN_attractor_based_on_six_datasets_/665768", "title"=>"Top 100 genes of the mitotic CIN attractor based on six datasets.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 01:36:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/965669"], "description"=>"<p>To evaluate the association between the mitotic CIN metagene expression and the 15-year survival, patients were divided into two groups: high mitotic CIN and low mitotic CIN. This binary expression level was determined by whether the mitotic CIN metagene expression value exceeding the mean of the patients. The <i>P</i> value of the association based on log-rank test is 1.8×10<sup>−8</sup>.</p>", "links"=>[], "tags"=>["mitotic", "cin", "attractor", "metagene", "cancer"], "article_id"=>635367, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Wei-Yi Cheng", "Tai-Hsien Ou Yang", "Dimitris Anastassiou"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1002920.g003", "stats"=>{"downloads"=>2, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Kaplan_Meier_curve_of_mitotic_CIN_attractor_metagene_in_breast_cancer_dataset_/635367", "title"=>"Kaplan-Meier curve of mitotic CIN attractor metagene in breast cancer dataset.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 11:32:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1005162"], "description"=>"<p>Top 100 genes of the lymphocyte-specific attractor based on six datasets.</p>", "links"=>[], "tags"=>["100", "genes", "lymphocyte-specific", "attractor"], "article_id"=>665789, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Wei-Yi Cheng", "Tai-Hsien Ou Yang", "Dimitris Anastassiou"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1002920.t003", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Top_100_genes_of_the_lymphocyte_specific_attractor_based_on_six_datasets_/665789", "title"=>"Top 100 genes of the lymphocyte-specific attractor based on six datasets.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 01:36:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/965988", "https://ndownloader.figshare.com/files/965989", "https://ndownloader.figshare.com/files/965990", "https://ndownloader.figshare.com/files/965991", "https://ndownloader.figshare.com/files/965992", "https://ndownloader.figshare.com/files/965993", "https://ndownloader.figshare.com/files/965994", "https://ndownloader.figshare.com/files/965995", "https://ndownloader.figshare.com/files/965996"], "description"=>"<div><p>Mining gene expression profiles has proven valuable for identifying signatures serving as surrogates of cancer phenotypes. However, the similarities of such signatures across different cancer types have not been strong enough to conclude that they represent a universal biological mechanism shared among multiple cancer types. Here we present a computational method for generating signatures using an iterative process that converges to one of several precise attractors defining signatures representing biomolecular events, such as cell transdifferentiation or the presence of an amplicon. By analyzing rich gene expression datasets from different cancer types, we identified several such biomolecular events, some of which are universally present in all tested cancer types in nearly identical form. Although the method is unsupervised, we show that it often leads to attractors with strong phenotypic associations. We present several such multi-cancer attractors, focusing on three that are prominent and sharply defined in all cases: a mesenchymal transition attractor strongly associated with tumor stage, a mitotic chromosomal instability attractor strongly associated with tumor grade, and a lymphocyte-specific attractor.</p> </div>", "links"=>[], "tags"=>["biomolecular", "cancer", "revealed", "attractor", "metagenes"], "article_id"=>635566, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Wei-Yi Cheng", "Tai-Hsien Ou Yang", "Dimitris Anastassiou"], "doi"=>["https://dx.doi.org/10.1371/journal.pcbi.1002920.s001", "https://dx.doi.org/10.1371/journal.pcbi.1002920.s002", "https://dx.doi.org/10.1371/journal.pcbi.1002920.s003", "https://dx.doi.org/10.1371/journal.pcbi.1002920.s004", "https://dx.doi.org/10.1371/journal.pcbi.1002920.s005", "https://dx.doi.org/10.1371/journal.pcbi.1002920.s006", "https://dx.doi.org/10.1371/journal.pcbi.1002920.s007", "https://dx.doi.org/10.1371/journal.pcbi.1002920.s008", "https://dx.doi.org/10.1371/journal.pcbi.1002920.s009"], "stats"=>{"downloads"=>45, "page_views"=>58, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Biomolecular_Events_in_Cancer_Revealed_by_Attractor_Metagenes__/635566", "title"=>"Biomolecular Events in Cancer Revealed by Attractor Metagenes", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-02-22 13:25:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/965673"], "description"=>"<p>For ER-negative patients, the expression of the attractor is highly protective (high expression implies longer survival, left). However, when multiple lymph nodes are already affected, the expression of the attractor has a reversed effect on survival. When we restrict the samples to those with more than five positive lymph nodes, higher expression of the lymphocyte-specific attractor implies shorter survival (right), although the association is not significant due to the limited number of samples (76).</p>", "links"=>[], "tags"=>["lymphocyte-specific", "attractor", "metagenes", "cancer"], "article_id"=>635370, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Wei-Yi Cheng", "Tai-Hsien Ou Yang", "Dimitris Anastassiou"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1002920.g004", "stats"=>{"downloads"=>0, "page_views"=>238, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Kaplan_Meier_curve_of_lymphocyte_specific_attractor_metagenes_in_breast_cancer_dataset_/635370", "title"=>"Kaplan-Meier curve of lymphocyte-specific attractor metagenes in breast cancer dataset.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 11:32:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/965667"], "description"=>"<p>The mesenchymal transition attractor metagene is most prominent in the early stage of breast cancer. The survival curve of the full dataset is insignificant (left). However, when the samples are restricted to only those at early stage (with no positive lymph nodes and tumor size less than 30 mm), the association between the mesenchymal transition attractor and the survival becomes significant (right), with <i>P</i> = 0.032.</p>", "links"=>[], "tags"=>["mesenchymal", "attractor", "metagenes", "cancer"], "article_id"=>635365, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Wei-Yi Cheng", "Tai-Hsien Ou Yang", "Dimitris Anastassiou"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1002920.g002", "stats"=>{"downloads"=>1, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Kaplan_Meier_curve_of_mesenchymal_transition_attractor_metagenes_in_breast_cancer_dataset_/635365", "title"=>"Kaplan-Meier curve of mesenchymal transition attractor metagenes in breast cancer dataset.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 11:32:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/1005125"], "description"=>"<p>Top 100 genes of the mesenchymal transition attractor based on six datasets.</p>", "links"=>[], "tags"=>["100", "genes", "mesenchymal", "attractor"], "article_id"=>665752, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Wei-Yi Cheng", "Tai-Hsien Ou Yang", "Dimitris Anastassiou"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1002920.t001", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Top_100_genes_of_the_mesenchymal_transition_attractor_based_on_six_datasets_/665752", "title"=>"Top 100 genes of the mesenchymal transition attractor based on six datasets.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 01:35:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/1005200"], "description"=>"<p>List of top ten genes in the chr8q24.3 and HER2 amplicons.</p>", "links"=>[], "tags"=>["genes", "her2"], "article_id"=>665829, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Wei-Yi Cheng", "Tai-Hsien Ou Yang", "Dimitris Anastassiou"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1002920.t005", "stats"=>{"downloads"=>3, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_List_of_top_ten_genes_in_the_chr8q24_3_and_HER2_amplicons_/665829", "title"=>"List of top ten genes in the chr8q24.3 and HER2 amplicons.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 01:37:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/965666"], "description"=>"<p>Gene expression data from 57 patients (GSE25104) were divided into two groups: high mesenchymal transition metagene level and low mesenchymal transition metagene level depending on whether the metagene expression value exceeding the mean of the 57 patients. The <i>P</i> value of the association was determined by log-rank test.</p>", "links"=>[], "tags"=>["curves", "mesenchymal", "attractor", "metagene", "squamous", "carcinoma"], "article_id"=>635364, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Wei-Yi Cheng", "Tai-Hsien Ou Yang", "Dimitris Anastassiou"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1002920.g001", "stats"=>{"downloads"=>2, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Kaplan_Meier_curves_of_mesenchymal_transition_attractor_metagene_in_oral_squamous_cell_carcinoma_dataset_/635364", "title"=>"Kaplan-Meier curves of mesenchymal transition attractor metagene in oral squamous cell carcinoma dataset.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 11:31:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/1005219"], "description"=>"<p>Top 50 genes of the estrogen receptor breast cancer attractor.</p>", "links"=>[], "tags"=>["50", "genes", "estrogen", "receptor", "cancer"], "article_id"=>665842, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Wei-Yi Cheng", "Tai-Hsien Ou Yang", "Dimitris Anastassiou"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1002920.t006", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Top_50_genes_of_the_estrogen_receptor_breast_cancer_attractor_/665842", "title"=>"Top 50 genes of the estrogen receptor breast cancer attractor.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 01:37:22"}

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Relative Metric

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