ALM

Hubs with Network Motifs Organize Modularity Dynamically in the Protein-Protein Interaction Network of Yeast

Publication Date: November 21, 2007
Journal: PLOS ONE
Authors: Guangxu Jin, Shihua Zhang, Xiang Sun Zhang & Luonan Chen
Volume: 2
Issue: 11
Pages: e1207
DOI: https://dx.plos.org/10.1371/journal.pone.0001207
Publisher URL: http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0001207
PubMed: http://www.ncbi.nlm.nih.gov/pubmed/18030341
PubMed Central: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2065901
Europe PMC: http://europepmc.org/abstract/MED/18030341
Web of Science: 000207459200020
Scopus: 43149087837
Mendeley: http://www.mendeley.com/research/hubs-network-motifs-organize-modularity-dynamically-proteinprotein-interaction-network-yeast

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{"title"=>"Hubs with network motifs organize modularity dynamically in the protein-protein interaction network of yeast", "type"=>"journal", "authors"=>[{"first_name"=>"Guangxu", "last_name"=>"Jin", "scopus_author_id"=>"7401563290"}, {"first_name"=>"Shihua", "last_name"=>"Zhang", "scopus_author_id"=>"35590912000"}, {"first_name"=>"Xiang Sun", "last_name"=>"Zhang", "scopus_author_id"=>"55961791600"}, {"first_name"=>"Luonan", "last_name"=>"Chen", "scopus_author_id"=>"26643448800"}], "year"=>2007, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-43149087837", "sgr"=>"43149087837", "pui"=>"351638149", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"18030341", "doi"=>"10.1371/journal.pone.0001207"}, "id"=>"fbc70fbe-46d2-346b-b7f5-d1dc89e2b9e4", "abstract"=>"BACKGROUND: It has been recognized that modular organization pervades biological complexity. Based on network analysis, 'party hubs' and 'date hubs' were proposed to understand the basic principle of module organization of biomolecular networks. However, recent study on hubs has suggested that there is no clear evidence for coexistence of 'party hubs' and 'date hubs'. Thus, an open question has been raised as to whether or not 'party hubs' and 'date hubs' truly exist in yeast interactome.\\n\\nMETHODOLOGY: In contrast to previous studies focusing on the partners of a hub or the individual proteins around the hub, our work aims to study the network motifs of a hub or interactions among individual proteins including the hub and its neighbors. Depending on the relationship between a hub's network motifs and protein complexes, we define two new types of hubs, 'motif party hubs' and 'motif date hubs', which have the same characteristics as the original 'party hubs' and 'date hubs' respectively. The network motifs of these two types of hubs display significantly different features in spatial distribution (or cellular localizations), co-expression in microarray data, controlling topological structure of network, and organizing modularity.\\n\\nCONCLUSION: By virtue of network motifs, we basically solved the open question about 'party hubs' and 'date hubs' which was raised by previous studies. Specifically, at the level of network motifs instead of individual proteins, we found two types of hubs, motif party hubs (mPHs) and motif date hubs (mDHs), whose network motifs display distinct characteristics on biological functions. In addition, in this paper we studied network motifs from a different viewpoint. That is, we show that a network motif should not be merely considered as an interaction pattern but be considered as an essential function unit in organizing modules of networks.", "link"=>"http://www.mendeley.com/research/hubs-network-motifs-organize-modularity-dynamically-proteinprotein-interaction-network-yeast", "reader_count"=>57, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>7, "Student > Doctoral Student"=>4, "Researcher"=>15, "Student > Ph. D. Student"=>19, "Student > Postgraduate"=>2, "Student > Master"=>4, "Student > Bachelor"=>1, "Lecturer > Senior Lecturer"=>2, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>7, "Student > Doctoral Student"=>4, "Researcher"=>15, "Student > Ph. D. Student"=>19, "Student > Postgraduate"=>2, "Student > Master"=>4, "Student > Bachelor"=>1, "Lecturer > Senior Lecturer"=>2, "Professor"=>2}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>4, "Biochemistry, Genetics and Molecular Biology"=>7, "Mathematics"=>3, "Agricultural and Biological Sciences"=>31, "Medicine and Dentistry"=>3, "Business, Management and Accounting"=>1, "Computer Science"=>7}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>31}, "Computer Science"=>{"Computer Science"=>7}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}, "Mathematics"=>{"Mathematics"=>3}, "Unspecified"=>{"Unspecified"=>4}}, "reader_count_by_country"=>{"United States"=>1, "Egypt"=>1, "Brazil"=>1, "United Kingdom"=>2, "Australia"=>1, "France"=>1, "Germany"=>1, "Spain"=>2}, "group_count"=>1}

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{"type"=>"COMMENT", "annotationUri"=>"info:doi/10.1371/annotation/fd03230c-330a-4892-b5bc-ed220471a8dd", "title"=>"Referee Comments: Referee 1 (Gábor Balázsi) ", "body"=>"Reviewer 1's Review (Gábor Balázsi)\n\n-----\n\nIn this manuscript, the authors analyze a high-confidence S. cerevisiae protein interaction network and introduce the novel concept of motif date hubs (mDH) and motif party hubs (mPH). They show that mPH and their constituent motifs co localize to the nucleus, while mDH and their constituents are separately localized, apart from the nucleus. Removal of mPHs has less influence on network connectivity than the removal of mDHs. mPHs are indicative of a function associated with \"nucleus\", while mDHs with various other functions. \n\nWhile this study required a significant amount of work, and lead to some potentially interesting results, I am reluctant in making a recommendation at this point, because the methods are not described with sufficient clarity and in sufficient detail to assure that the results are correct. The manuscript is poorly written, and difficult to read. The sections do not serve a clear role, for example the Discussion continues presenting results instead of analyzing and evaluating what was described before. The Results section contains many unnecessary details, while important details are vaguely described or omitted. The reference list is incomplete, and the Methods section is vague. The manuscript should be rewritten, necessary definitions included, and unnecessary details moved to a Supplementary Text. Towards the end, the writing becomes especially poor, at least I was unable to follow what the authors were trying to describe about the pathways. \n\nFor example, the authors refer to the earlier results by Han et al. They should describe more clearly the earlier results so that the reader does not have to re-read it to clarify what the hubs' average PCC is. Quantities such as Complex_ratio_same should be defined by formulas in the Methods, and should be defined differently (in words) and clearly in the Results, so that the reader understands the essence of this measure without reading the Methods. Results are described repeatedly, without adding new insight (the fact that mPHs and their constituents localize to the nucleus is mentioned repeatedly). All of the results sections should be reduced in size, following three questions: 1. What was the question asked? 2. What were the methods used to answer the question? 3. What was the outcome of the analysis? \n\nThe two types of hubs are essential in this manuscript, but are defined vaguely and in the wrong place in the Results (the reader has to refer to the Methods to understand what they are). mPHs and mDHs should be defined at the very beginning of the results section. Moreover, it should be clarified how they relate to the DHs and PHs defined by Han et al (is there any significant overlap? Why are they called similarly?). \n\nThe Methods section is incomplete and vague. Concepts should be very clearly described, and formulas given. Most importantly, the authors should clarify how they handle proteins that are parts of multiple complexes, or those that that belong to multiple subcellular localizations. They should tell exactly what motifs they are using (or even show them as part of a figure), not only give their numbers 238 and 13260. \n\nThe concept of \"motif density\" is clearly related to the \"clustering coefficient\", and it might not be necessary. The authors should calculate the \"clustering coefficient\" for nearest and next-nearest neighbors, and see how their results compare with using the \"motif density\". Relevant literature that should be consulted and cited includes Wuchty et al, Nat. Genetics 2003, Dobrin et al., BMC Bioinformatics 2004, Vazquez et al., PNAS 2004. \n\n-----\n\nN.B. These are the general comments made by the reviewer when reviewing this paper in light of which the manuscript was revised. Specific points addressed during revision of the paper are not shown.\n", "isRemoved"=>false, "created"=>"2007-11-22T10:02:00Z", "lastModified"=>"2007-11-22T10:02:00Z", "creator"=>{"userId"=>"80539"}, "highlightedText"=>"", "competingInterestStatement"=>{"creatorWasPrompted"=>false, "hasCompetingInterests"=>false}, "parentArticle"=>{"doi"=>"info:doi/10.1371/journal.pone.0001207", "state"=>"published", "journals"=>{"PLoSONE"=>{"journalKey"=>"PLoSONE", "eIssn"=>"1932-6203", "title"=>"PLOS ONE"}}}, "replyTreeSize"=>0, "mostRecentActivity"=>"2007-11-22T10:02:00Z", "replies"=>[]}

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Figshare 4802 Apr 20:58 UTC

Figshare

{"files"=>["https://ndownloader.figshare.com/files/941125"], "description"=>"The hub overlap of FYI and HCfyi and the correctly divided mPHs and mDHs in the overlap.", "links"=>[], "tags"=>["hub", "overlap", "fyi", "divided", "mphs", "mdhs"], "article_id"=>611536, "categories"=>["Medicine"], "users"=>["Guangxu Jin", "Shihua Zhang", "Xiang-Sun Zhang", "Luonan Chen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001207.g001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_hub_overlap_of_FYI_and_HC_fyi_and_the_correctly_divided_mPHs_and_mDHs_in_the_overlap_/611536", "title"=>"The hub overlap of FYI and HCfyi and the correctly divided mPHs and mDHs in the overlap.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2007-11-21 00:25:36"}
{"files"=>["https://ndownloader.figshare.com/files/941300"], "description"=>"(A) The case of deleting mPHs and their motifs. In this case, the main components remain (the points in the same color are in the same component). (B) The case of deleting mDHs and their network motifs. Deleting the mDHs and their motif proteins causes the main components to disappear (the points in the same color are in the same component). (C) Deleting hubs one by one. The HCfyi network is tolerant for the deletion of mPHs with their motifs. However, it is not tolerant for the deletion of mDHs with their motifs. (D) Deleting a randomly chosen set of 98 hubs with their motifs. We repeat the removal of 98 hubs with their motifs randomly for 1000 times. The sizes of the largest remaining components are all less than 555 that are the size of the largest component after removing the mPHs with their motifs. The sizes of the largest remaining components are all larger than 47 that are the size of the largest component after removing the mDHs with their motifs. Empirical P values are both less than 10−3. Biolayout <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001207#pone.0001207-Enright1\" target=\"_blank\">[53]</a> has been used to produce the figures in (A) and (B).", "links"=>[], "tags"=>["mphs", "motifs", "mdhs"], "article_id"=>611721, "categories"=>["Medicine"], "users"=>["Guangxu Jin", "Shihua Zhang", "Xiang-Sun Zhang", "Luonan Chen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001207.g004", "stats"=>{"downloads"=>3, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Deleting_mPHs_with_their_motifs_and_mDHs_with_their_motifs_respectively_/611721", "title"=>"Deleting mPHs with their motifs and mDHs with their motifs respectively.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2007-11-21 00:28:41"}
{"files"=>["https://ndownloader.figshare.com/files/941564"], "description"=>"Sizes and Numbers of the network components after removal of mPHs and mDHs respectively", "links"=>[], "tags"=>["numbers", "components", "mphs", "mdhs"], "article_id"=>611982, "categories"=>["Medicine"], "users"=>["Guangxu Jin", "Shihua Zhang", "Xiang-Sun Zhang", "Luonan Chen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001207.t001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Sizes_and_Numbers_of_the_network_components_after_removal_of_mPHs_and_mDHs_respectively_/611982", "title"=>"Sizes and Numbers of the network components after removal of mPHs and mDHs respectively", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2007-11-21 00:33:02"}
{"files"=>["https://ndownloader.figshare.com/files/941207"], "description"=>"(A) Cellular localizations of mDHs. (B) Cellular localizations of mPHs.", "links"=>[], "tags"=>["localizations", "mdhs"], "article_id"=>611632, "categories"=>["Medicine"], "users"=>["Guangxu Jin", "Shihua Zhang", "Xiang-Sun Zhang", "Luonan Chen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001207.g003", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_localizations_for_mDHs_and_mPHs_/611632", "title"=>"The localizations for mDHs and mPHs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2007-11-21 00:27:12"}
{"files"=>["https://ndownloader.figshare.com/files/941532"], "description"=>"*Mann-Whitney U test <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001207#pone.0001207-Bernard1\" target=\"_blank\">[54]</a>.", "links"=>[], "tags"=>["differences", "samcs", "mdhs", "mphs", "microarray"], "article_id"=>611950, "categories"=>["Medicine"], "users"=>["Guangxu Jin", "Shihua Zhang", "Xiang-Sun Zhang", "Luonan Chen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001207.t003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Statistic_significance_for_the_differences_of_SAMCs_between_mDHs_and_mPHs_in_Microarray_data_/611950", "title"=>"Statistic significance for the differences of SAMCs between mDHs and mPHs in Microarray data", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2007-11-21 00:32:30"}
{"files"=>["https://ndownloader.figshare.com/files/941366"], "description"=>"In the middle of the panel, the red circles are abstract representations of pathways, where 14 smaller ones only connect with 6 mDHs (circles in light blue), and 26 larger ones connect with not only mDHs in blue circles (except the light blue one at the top of the panel) but also mPHs in orange circles. If more than one motif proteins of an mDH or an mPH are involved in one pathway, we connect the mDH or mPH with the pathway by an edge. Biolayout <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001207#pone.0001207-Enright1\" target=\"_blank\">[53]</a> has been used to produce the figure.", "links"=>[], "tags"=>["motifs", "linking", "pathways", "mdhs"], "article_id"=>611786, "categories"=>["Medicine"], "users"=>["Guangxu Jin", "Shihua Zhang", "Xiang-Sun Zhang", "Luonan Chen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001207.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Network_motifs_linking_up_pathways_with_mDHs_and_mPHs_/611786", "title"=>"Network motifs linking up pathways with mDHs and mPHs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2007-11-21 00:29:46"}
{"files"=>["https://ndownloader.figshare.com/files/941469"], "description"=>"The proteins and interactions in HCfyi and in all network motifs of HCfyi respectively.", "links"=>[], "tags"=>["proteins", "interactions", "motifs"], "article_id"=>611891, "categories"=>["Medicine"], "users"=>["Guangxu Jin", "Shihua Zhang", "Xiang-Sun Zhang", "Luonan Chen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001207.g006", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_proteins_and_interactions_in_HC_fyi_and_in_all_network_motifs_of_HC_fyi_respectively_/611891", "title"=>"The proteins and interactions in HCfyi and in all network motifs of HCfyi respectively.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2007-11-21 00:31:31"}
{"files"=>["https://ndownloader.figshare.com/files/463693", "https://ndownloader.figshare.com/files/463772", "https://ndownloader.figshare.com/files/463817", "https://ndownloader.figshare.com/files/463826", "https://ndownloader.figshare.com/files/463841"], "description"=>"<div><h3>Background</h3>It has been recognized that modular organization pervades biological complexity. Based on network analysis, ‘party hubs’ and ‘date hubs’ were proposed to understand the basic principle of module organization of biomolecular networks. However, recent study on hubs has suggested that there is no clear evidence for coexistence of ‘party hubs’ and ‘date hubs’. Thus, an open question has been raised as to whether or not ‘party hubs’ and ‘date hubs’ truly exist in yeast interactome.<h3>Methodology</h3>In contrast to previous studies focusing on the partners of a hub or the individual proteins around the hub, our work aims to study the network motifs of a hub or interactions among individual proteins including the hub and its neighbors. Depending on the relationship between a hub's network motifs and protein complexes, we define two new types of hubs, ‘motif party hubs’ and ‘motif date hubs’, which have the same characteristics as the original ‘party hubs’ and ‘date hubs’ respectively. The network motifs of these two types of hubs display significantly different features in spatial distribution (or cellular localizations), co-expression in microarray data, controlling topological structure of network, and organizing modularity.<h3>Conclusion</h3>By virtue of network motifs, we basically solved the open question about ‘party hubs’ and ‘date hubs’ which was raised by previous studies. Specifically, at the level of network motifs instead of individual proteins, we found two types of hubs, motif party hubs (mPHs) and motif date hubs (mDHs), whose network motifs display distinct characteristics on biological functions. In addition, in this paper we studied network motifs from a different viewpoint. That is, we show that a network motif should not be merely considered as an interaction pattern but be considered as an essential function unit in organizing modules of networks.</div>", "links"=>[], "tags"=>["hubs", "motifs", "modularity", "dynamically", "protein-protein", "yeast"], "article_id"=>151393, "categories"=>["Medicine"], "users"=>["Guangxu Jin", "Shihua Zhang", "Xiang-Sun Zhang", "Luonan Chen"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0001207.s001", "https://dx.doi.org/10.1371/journal.pone.0001207.s002", "https://dx.doi.org/10.1371/journal.pone.0001207.s003", "https://dx.doi.org/10.1371/journal.pone.0001207.s004", "https://dx.doi.org/10.1371/journal.pone.0001207.s005"], "stats"=>{"downloads"=>17, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Hubs_with_Network_Motifs_Organize_Modularity_Dynamically_in_the_Protein_Protein_Interaction_Network_of_Yeast/151393", "title"=>"Hubs with Network Motifs Organize Modularity Dynamically in the Protein-Protein Interaction Network of Yeast", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2007-11-21 00:23:13"}
{"files"=>["https://ndownloader.figshare.com/files/941502"], "description"=>"There are totally 66 pathways in KEGG appearing in HCfyi network.", "links"=>[], "tags"=>["pathways"], "article_id"=>611922, "categories"=>["Medicine"], "users"=>["Guangxu Jin", "Shihua Zhang", "Xiang-Sun Zhang", "Luonan Chen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001207.t002", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Linking_with_signal_pathways_by_network_motifs_/611922", "title"=>"Linking with signal pathways by network motifs", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2007-11-21 00:32:02"}
{"files"=>["https://ndownloader.figshare.com/files/941165"], "description"=>"The spatial distribution of hubs.", "links"=>[], "tags"=>["spatial"], "article_id"=>611593, "categories"=>["Medicine"], "users"=>["Guangxu Jin", "Shihua Zhang", "Xiang-Sun Zhang", "Luonan Chen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001207.g002", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_spatial_distribution_of_hubs_/611593", "title"=>"The spatial distribution of hubs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2007-11-21 00:26:33"}

PMC Usage Stats 126617 Sep 13:35 UTC

PMC Usage Stats | Further Information

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Relative Metric 122894412 Apr 18:42 UTC

Relative Metric

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F1000Prime09 Oct 10:43 UTC

F1000Prime

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