The Importance of Bottlenecks in Protein Networks: Correlation with Gene Essentiality and Expression Dynamics
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{"title"=>"The importance of bottlenecks in protein networks: Correlation with gene essentiality and expression dynamics", "type"=>"journal", "authors"=>[{"first_name"=>"Haiyuan", "last_name"=>"Yu", "scopus_author_id"=>"8734667400"}, {"first_name"=>"Philip M.", "last_name"=>"Kim", "scopus_author_id"=>"34167971300"}, {"first_name"=>"Emmett", "last_name"=>"Sprecher", "scopus_author_id"=>"16246148200"}, {"first_name"=>"Valery", "last_name"=>"Trifonov", "scopus_author_id"=>"7005416911"}, {"first_name"=>"Mark", "last_name"=>"Gerstein", "scopus_author_id"=>"24755400900"}], "year"=>2007, "source"=>"PLoS Computational Biology", "identifiers"=>{"issn"=>"1553734X", "scopus"=>"2-s2.0-34247622363", "pui"=>"46683453", "doi"=>"10.1371/journal.pcbi.0030059", "isbn"=>"1553-7358 (Electronic)", "sgr"=>"34247622363", "pmid"=>"17447836"}, "id"=>"70676eb6-23d0-3957-95d7-7c27037ae709", "abstract"=>"It has been a long-standing goal in systems biology to find relations between the topological properties and functional features of protein networks. However, most of the focus in network studies has been on highly connected proteins (\"hubs\"). As a complementary notion, it is possible to define bottlenecks as proteins with a high betweenness centrality (i.e., network nodes that have many \"shortest paths\" going through them, analogous to major bridges and tunnels on a highway map). Bottlenecks are, in fact, key connector proteins with surprising functional and dynamic properties. In particular, they are more likely to be essential proteins. In fact, in regulatory and other directed networks, betweenness (i.e., \"bottleneck-ness\") is a much more significant indicator of essentiality than degree (i.e., \"hub-ness\"). Furthermore, bottlenecks correspond to the dynamic components of the interaction network-they are significantly less well coexpressed with their neighbors than non-bottlenecks, implying that expression dynamics is wired into the network topology.", "link"=>"http://www.mendeley.com/research/importance-bottlenecks-protein-networks-correlation-gene-essentiality-expression-dynamics", "reader_count"=>471, "reader_count_by_academic_status"=>{"Unspecified"=>10, "Professor > Associate Professor"=>34, "Researcher"=>126, "Student > Doctoral Student"=>21, "Student > Ph. D. Student"=>152, "Student > Postgraduate"=>17, "Student > Master"=>51, "Other"=>12, "Student > Bachelor"=>25, "Lecturer"=>5, "Lecturer > Senior Lecturer"=>2, "Professor"=>16}, "reader_count_by_user_role"=>{"Unspecified"=>10, "Professor > Associate Professor"=>34, "Researcher"=>126, "Student > Doctoral Student"=>21, "Student > Ph. D. Student"=>152, "Student > Postgraduate"=>17, "Student > Master"=>51, "Other"=>12, "Student > Bachelor"=>25, "Lecturer"=>5, "Lecturer > Senior Lecturer"=>2, "Professor"=>16}, "reader_count_by_subject_area"=>{"Unspecified"=>20, "Agricultural and Biological Sciences"=>284, "Philosophy"=>2, "Veterinary Science and Veterinary Medicine"=>1, "Chemistry"=>6, "Computer Science"=>57, "Earth and Planetary Sciences"=>1, "Engineering"=>11, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>53, "Mathematics"=>11, "Medicine and Dentistry"=>15, "Pharmacology, Toxicology and Pharmaceutical Science"=>2, "Physics and Astronomy"=>4, "Psychology"=>1, "Social Sciences"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>15}, "Social Sciences"=>{"Social Sciences"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>4}, "Psychology"=>{"Psychology"=>1}, "Mathematics"=>{"Mathematics"=>11}, "Unspecified"=>{"Unspecified"=>20}, "Environmental Science"=>{"Environmental Science"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>2}, "Engineering"=>{"Engineering"=>11}, "Chemistry"=>{"Chemistry"=>6}, "Earth and Planetary Sciences"=>{"Earth and Planetary Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>284}, "Computer Science"=>{"Computer Science"=>57}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>53}, "Philosophy"=>{"Philosophy"=>2}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"Republic of Singapore"=>1, "Hungary"=>1, "United States"=>21, "Japan"=>4, "United Kingdom"=>16, "Switzerland"=>1, "India"=>6, "Spain"=>9, "Russia"=>1, "Canada"=>1, "South Korea"=>1, "Netherlands"=>1, "Turkey"=>2, "Korea (South)"=>1, "China"=>1, "Brazil"=>8, "Denmark"=>1, "Poland"=>1, "Italy"=>4, "Slovenia"=>1, "France"=>4, "Chile"=>1, "Australia"=>1, "Germany"=>7}, "group_count"=>25}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/950514"], "description"=>"<p>Histograms of the average correlation coefficient of the expression profile of any given gene with its direct interaction partners. Expression dynamics for all four categories of nodes are shown in <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.0030059#pcbi-0030059-sg007\" target=\"_blank\">Figure S7</a>.</p>", "links"=>[], "tags"=>["Computational biology", "Evolutionary biology"], "article_id"=>620836, "categories"=>["Biological Sciences", "Evolutionary Biology"], "users"=>["Haiyuan Yu", "Philip M Kim", "Emmett Sprecher", "Valery Trifonov", "Mark Gerstein"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.0030059.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_Dynamics_of_Hub_8211_Nonbottlenecks_and_Hub_8211_Bottlenecks_/620836", "title"=>"Expression Dynamics of Hub–Nonbottlenecks and Hub–Bottlenecks", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2007-04-20 00:13:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/950388"], "description"=>"<div><p>(A) Bottlenecks tend to be essential genes in both interaction and regulatory networks. <i>p-</i>Values measure the statistical significance of the different essentialities between bottlenecks and nonbottlenecks.</p><p>(B) Essentiality of different categories of proteins. NH-NB, nonhub–nonbottlenecks; H-NB, hub–nonbottlenecks; B-NH, nonhub–bottlenecks; BH, hub–bottlenecks. <i>p-</i>Values measure the statistical significance of the different essentialities between different categories of proteins against nonhub–nonbottlenecks using cumulative binomial distributions (see <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.0030059#s4\" target=\"_blank\">Methods</a>).</p></div>", "links"=>[], "tags"=>["essentiality", "categories", "proteins"], "article_id"=>620711, "categories"=>["Biological Sciences", "Evolutionary Biology"], "users"=>["Haiyuan Yu", "Philip M Kim", "Emmett Sprecher", "Valery Trifonov", "Mark Gerstein"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.0030059.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_Essentiality_among_Various_Categories_of_Proteins_within_Interaction_and_Regulatory_Networks_/620711", "title"=>"Comparison of Essentiality among Various Categories of Proteins within Interaction and Regulatory Networks", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2007-04-20 00:11:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/950454"], "description"=>"<p>To find all proteins participating in signaling transduction pathways (i.e., the bar “Signal”), we manually went through all available pathways in KEGG and collected all proteins in them. Since this is a very small dataset, we further included all proteins, more than half of whose interacting partners are involved in signaling transduction pathways in KEGG. This inclusion is reasonable because the general belief is that interacting proteins share the same function. The fraction of essential genes among nonhub–nonbottlenecks is used as the random expectation, which is also indicated by the horizontal line. <i>p-</i>Values measure the statistical significance of the different essentialities of different categories of nonhub–bottlenecks relative to the random expectation. The bar “MIPS” refers to nonhub–bottlenecks involved in the complexes defined by the MIPS complex catalog. The bar “Permanent” refers to nonhub–bottlenecks involved in permanent interactions. The bar “Transient” refers to nonhub–bottlenecks only involved in transient interactions. The bar “All” refers to all nonhub–bottlenecks. *<i>p-</i>Value above the bar “Transient” measures the statistical significance of transient nonhub–bottlenecks being less essential than random.</p>", "links"=>[], "tags"=>["categories"], "article_id"=>620775, "categories"=>["Biological Sciences", "Evolutionary Biology"], "users"=>["Haiyuan Yu", "Philip M Kim", "Emmett Sprecher", "Valery Trifonov", "Mark Gerstein"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.0030059.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Essentialities_of_Different_Categories_of_Nonhub_8211_Bottlenecks_in_the_Interaction_Network_/620775", "title"=>"Essentialities of Different Categories of Nonhub–Bottlenecks in the Interaction Network", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2007-04-20 00:12:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/950591"], "description"=>"<p>Cak1p is a cyclin-dependent kinase-activating kinase involved in two key signaling-transduction pathways: cell cycle and sporulation.</p>", "links"=>[], "tags"=>["Computational biology", "Evolutionary biology"], "article_id"=>620909, "categories"=>["Biological Sciences", "Evolutionary Biology"], "users"=>["Haiyuan Yu", "Philip M Kim", "Emmett Sprecher", "Valery Trifonov", "Mark Gerstein"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.0030059.g005", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_Biological_Example_of_a_Nonhub_8211_Bottleneck_in_the_Interaction_Network_/620909", "title"=>"A Biological Example of a Nonhub–Bottleneck in the Interaction Network", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2007-04-20 00:15:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/468163", "https://ndownloader.figshare.com/files/468213", "https://ndownloader.figshare.com/files/468255", "https://ndownloader.figshare.com/files/468329", "https://ndownloader.figshare.com/files/468390", "https://ndownloader.figshare.com/files/468457", "https://ndownloader.figshare.com/files/468581", "https://ndownloader.figshare.com/files/468677", "https://ndownloader.figshare.com/files/468751", "https://ndownloader.figshare.com/files/468826"], "description"=>"<div><p>It has been a long-standing goal in systems biology to find relations between the topological properties and functional features of protein networks. However, most of the focus in network studies has been on highly connected proteins (“hubs”). As a complementary notion, it is possible to define bottlenecks as proteins with a high betweenness centrality (i.e., network nodes that have many “shortest paths” going through them, analogous to major bridges and tunnels on a highway map). Bottlenecks are, in fact, key connector proteins with surprising functional and dynamic properties. In particular, they are more likely to be essential proteins. In fact, in regulatory and other directed networks, betweenness (i.e., “bottleneck-ness”) is a much more significant indicator of essentiality than degree (i.e., “hub-ness”). Furthermore, bottlenecks correspond to the dynamic components of the interaction network—they are significantly less well coexpressed with their neighbors than nonbottlenecks, implying that expression dynamics is wired into the network topology.</p></div>", "links"=>[], "tags"=>["bottlenecks", "essentiality"], "article_id"=>152302, "categories"=>["Biological Sciences", "Evolutionary Biology"], "users"=>["Haiyuan Yu", "Philip M Kim", "Emmett Sprecher", "Valery Trifonov", "Mark Gerstein"], "doi"=>["https://dx.doi.org/10.1371/journal.pcbi.0030059.sg001", "https://dx.doi.org/10.1371/journal.pcbi.0030059.sg002", "https://dx.doi.org/10.1371/journal.pcbi.0030059.sg003", "https://dx.doi.org/10.1371/journal.pcbi.0030059.sg004", "https://dx.doi.org/10.1371/journal.pcbi.0030059.sg005", "https://dx.doi.org/10.1371/journal.pcbi.0030059.sg006", "https://dx.doi.org/10.1371/journal.pcbi.0030059.sg007", "https://dx.doi.org/10.1371/journal.pcbi.0030059.st001", "https://dx.doi.org/10.1371/journal.pcbi.0030059.st002", "https://dx.doi.org/10.1371/journal.pcbi.0030059.st003"], "stats"=>{"downloads"=>20, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_Importance_of_Bottlenecks_in_Protein_Networks_Correlation_with_Gene_Essentiality_and_Expression_Dynamics/152302", "title"=>"The Importance of Bottlenecks in Protein Networks: Correlation with Gene Essentiality and Expression Dynamics", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2007-04-20 00:38:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/950299"], "description"=>"<p>Four nodes with different colors represent examples of the four categories defined by degree and betweenness. Please note that every node in the network belongs to one of the four categories. However, in this schematic, we only point out the categories of the four example nodes.</p>", "links"=>[], "tags"=>["bottleneck", "categories", "nodes"], "article_id"=>620623, "categories"=>["Biological Sciences", "Evolutionary Biology"], "users"=>["Haiyuan Yu", "Philip M Kim", "Emmett Sprecher", "Valery Trifonov", "Mark Gerstein"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.0030059.g001", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematic_Showing_a_Bottleneck_and_the_Four_Categories_of_Nodes_in_a_Network_/620623", "title"=>"Schematic Showing a Bottleneck and the Four Categories of Nodes in a Network", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2007-04-20 00:10:23"}

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Relative Metric

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