Mapping Protein Interactions between Dengue Virus and Its Human and Insect Hosts
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{"title"=>"Mapping protein interactions between dengue virus and its human and insect hosts", "type"=>"journal", "authors"=>[{"first_name"=>"Janet M.", "last_name"=>"Doolittle", "scopus_author_id"=>"35956117500"}, {"first_name"=>"Shawn M.", "last_name"=>"Gomez", "scopus_author_id"=>"7102183635"}], "year"=>2011, "source"=>"PLoS Neglected Tropical Diseases", "identifiers"=>{"issn"=>"1935-2735", "scopus"=>"2-s2.0-79952459772", "sgr"=>"79952459772", "pui"=>"361411276", "isbn"=>"1935-2735 (Electronic)\\r1935-2727 (Linking)", "pmid"=>"21358811", "doi"=>"10.1371/journal.pntd.0000954"}, "id"=>"f8333b75-8ee2-372a-8543-b651d86d8ca7", "abstract"=>"BACKGROUND: Dengue fever is an increasingly significant arthropod-borne viral disease, with at least 50 million cases per year worldwide. As with other viral pathogens, dengue virus is dependent on its host to perform the bulk of functions necessary for viral survival and replication. To be successful, dengue must manipulate host cell biological processes towards its own ends, while avoiding elimination by the immune system. Protein-protein interactions between the virus and its host are one avenue through which dengue can connect and exploit these host cellular pathways and processes.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: We implemented a computational approach to predict interactions between Dengue virus (DENV) and both of its hosts, Homo sapiens and the insect vector Aedes aegypti. Our approach is based on structural similarity between DENV and host proteins and incorporates knowledge from the literature to further support a subset of the predictions. We predict over 4,000 interactions between DENV and humans, as well as 176 interactions between DENV and A. aegypti. Additional filtering based on shared Gene Ontology cellular component annotation reduced the number of predictions to approximately 2,000 for humans and 18 for A. aegypti. Of 19 experimentally validated interactions between DENV and humans extracted from the literature, this method was able to predict nearly half (9). Additional predictions suggest specific interactions between virus and host proteins relevant to interferon signaling, transcriptional regulation, stress, and the unfolded protein response.\\n\\nCONCLUSIONS/SIGNIFICANCE: Dengue virus manipulates cellular processes to its advantage through specific interactions with the host's protein interaction network. The interaction networks presented here provide a set of hypothesis for further experimental investigation into the DENV life cycle as well as potential therapeutic targets.", "link"=>"http://www.mendeley.com/research/mapping-protein-interactions-between-dengue-virus-human-insect-hosts-6", "reader_count"=>126, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>3, "Student > Doctoral Student"=>7, "Researcher"=>27, "Student > Ph. D. Student"=>37, "Student > Postgraduate"=>3, "Other"=>9, "Student > Master"=>20, "Student > Bachelor"=>10, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>2, "Professor"=>4}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>3, "Student > Doctoral Student"=>7, "Researcher"=>27, "Student > Ph. D. Student"=>37, "Student > Postgraduate"=>3, "Other"=>9, "Student > Master"=>20, "Student > Bachelor"=>10, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>2, "Professor"=>4}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Agricultural and Biological Sciences"=>74, "Arts and Humanities"=>1, "Business, Management and Accounting"=>1, "Veterinary Science and Veterinary Medicine"=>1, "Chemistry"=>2, "Computer Science"=>3, "Engineering"=>2, "Biochemistry, Genetics and Molecular Biology"=>17, "Mathematics"=>1, "Medicine and Dentistry"=>9, "Design"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Physics and Astronomy"=>4, "Social Sciences"=>1, "Immunology and Microbiology"=>4}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>9}, "Social Sciences"=>{"Social Sciences"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>4}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>4}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Arts and Humanities"=>{"Arts and Humanities"=>1}, "Design"=>{"Design"=>1}, "Engineering"=>{"Engineering"=>2}, "Chemistry"=>{"Chemistry"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>74}, "Computer Science"=>{"Computer Science"=>3}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>17}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"United States"=>6, "Japan"=>2, "United Kingdom"=>2, "Belarus"=>1, "Portugal"=>1, "Spain"=>1, "French Polynesia"=>1, "China"=>1, "Brazil"=>3, "Mexico"=>2, "Italy"=>1, "France"=>2, "Indonesia"=>1}, "group_count"=>4}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/798809"], "description"=>"<p>(A) Predicted interactions between DENV and orthologous pairs of <i>A.aegypti</i> and human proteins. The human protein is listed first, followed by its ortholog in <i>A.aegypti</i> which is also predicted to interact with the DENV protein. (B) GO biological process terms enriched among the interactions predicted to be conserved between human and <i>A.aegypti</i>. “reg synaptic growth at junction” is an abbreviation for “regulation of synaptic growth at neuromuscular junction,” and “cell morph in differentiation” stands for “cell morphogenesis involved in differentiation.”</p>", "links"=>[], "tags"=>["orthologous"], "article_id"=>469184, "categories"=>["Biochemistry", "Infectious Diseases", "Molecular Biology", "Medicine"], "users"=>["Janet M. Doolittle", "Shawn M. Gomez"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000954.g008", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Predicted_orthologous_interactions_/469184", "title"=>"Predicted orthologous interactions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-02-15 02:33:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/798458"], "description"=>"<p>Predicted interactions between DENV and <i>A.aegypti</i> where the DENV protein and its target share at least one GO CC term. Solid lines represent interactions for which the <i>A.aegypti</i> protein is a host factor.</p>", "links"=>[], "tags"=>["interactions", "cc"], "article_id"=>468832, "categories"=>["Biochemistry", "Infectious Diseases", "Molecular Biology", "Medicine"], "users"=>["Janet M. Doolittle", "Shawn M. Gomez"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000954.g004", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Predicted_interactions_in_A_aegypti_after_CC_filtering_/468832", "title"=>"Predicted interactions in <i>A.aegypti</i> after CC filtering.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-02-15 02:27:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/798286"], "description"=>"<p>(A) Enriched GO biological process terms. (B) Enriched GO molecular function terms. Blue bars represent terms enriched among human target proteins, red is terms enriched among hDENV-similar proteins, light blue is terms for <i>A. aegypti</i> targets, and pink is for terms from dDENV-similar proteins. When more than ten terms were enriched for a set of proteins, only the ten most significant terms are shown. Bonferroni corrected p-values were transformed by . The following abbreviations are used: “reg” is “regulation of,” “pos” is “positive,” “neg” is “negative,” “proc” is “process,” “peptidase activity L-aa peptides” is “peptidase activity acting on L-amino acid peptides,” and “phosphotrans alcohol group” is “phosphotransferase activity alcohol group as acceptor.” Brackets delineate the two host species.</p>", "links"=>[], "tags"=>["enrichment"], "article_id"=>468664, "categories"=>["Biochemistry", "Infectious Diseases", "Molecular Biology", "Medicine"], "users"=>["Janet M. Doolittle", "Shawn M. Gomez"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000954.g002", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_GO_term_enrichment_of_host_proteins_/468664", "title"=>"GO term enrichment of host proteins.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-02-15 02:24:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/798529"], "description"=>"<p>Potential interactions between DENV proteins and key components of the Unfolded Protein Response (UPR) and ER stress. See text for additional details.</p>", "links"=>[], "tags"=>["er"], "article_id"=>468908, "categories"=>["Biochemistry", "Infectious Diseases", "Molecular Biology", "Medicine"], "users"=>["Janet M. Doolittle", "Shawn M. Gomez"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000954.g005", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DENV_and_ER_Stress_/468908", "title"=>"DENV and ER Stress.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-02-15 02:28:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/798206"], "description"=>"<p>(A) Predictions for the human host. Interactions between DENV proteins and human targets is predicted on the basis of structural similarity between the DENV protein and an hDENV-similar protein, and the hDENV-similar protein's known interaction with the human target. (B) Predictions for the insect host are made in a similar manner as (A), except for the additional step of finding orthologs of the <i>D. melanogaster</i> target proteins in the real host of interest, <i>A. aegypti</i>.</p>", "links"=>[], "tags"=>["biochemistry/structural genomics", "computational biology/protein homology detection", "computational biology/protein structure prediction", "computational biology/signaling networks", "computational biology/systems biology", "infectious diseases/neglected tropical diseases", "infectious diseases/tropical and travel-associated diseases", "infectious diseases/viral infections", "molecular biology/bioinformatics", "virology/immune evasion", "virology/viral replication and gene regulation"], "article_id"=>468561, "categories"=>["Biochemistry", "Infectious Diseases", "Molecular Biology", "Medicine"], "users"=>["Janet M. Doolittle", "Shawn M. Gomez"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000954.g001", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Diagram_of_approach_/468561", "title"=>"Diagram of approach.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-02-15 02:22:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/798376"], "description"=>"<p>Predicted interactions between DENV and its hosts. Only predictions that were already known and those involving host factors are shown. Solid lines represent interactions for which the host protein was found by an siRNA screen to be involved in DENV infection, while dashed lines indicate that it is not a known host factor. Red lines represent interactions already known from the literature.</p>", "links"=>[], "tags"=>["interactions"], "article_id"=>468755, "categories"=>["Biochemistry", "Infectious Diseases", "Molecular Biology", "Medicine"], "users"=>["Janet M. Doolittle", "Shawn M. Gomez"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000954.g003", "stats"=>{"downloads"=>3, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Predicted_interactions_with_literature_support_/468755", "title"=>"Predicted interactions with literature support.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-02-15 02:25:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/798610"], "description"=>"<p>(A) Structural similarity between NS3 and RAD51 (1n0wA <a href=\"http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000954#pntd.0000954-Pellegrini1\" target=\"_blank\">[86]</a>). (B) Structural similarity between NS3 and TK1 (1w4rA <a href=\"http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000954#pntd.0000954-Birringer1\" target=\"_blank\">[87]</a>). (C) Structural similarity between NS3 and APAF1 (1z6tC <a href=\"http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000954#pntd.0000954-Riedl1\" target=\"_blank\">[88]</a>). (D) Structural similarity between NS3 and DDX5 (3fe2A <a href=\"http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000954#pntd.0000954-Karlberg1\" target=\"_blank\">[89]</a>). NS3 (2bhrA <a href=\"http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000954#pntd.0000954-Xu1\" target=\"_blank\">[90]</a>) is shown in red.</p>", "links"=>[], "tags"=>["similarities", "ns3", "proteins"], "article_id"=>468981, "categories"=>["Biochemistry", "Infectious Diseases", "Molecular Biology", "Medicine"], "users"=>["Janet M. Doolittle", "Shawn M. Gomez"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000954.g006", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Structural_similarities_between_NS3_and_human_proteins_involved_in_apoptosis_/468981", "title"=>"Structural similarities between NS3 and human proteins involved in apoptosis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-02-15 02:29:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/798956"], "description"=>"<p>Counts are given for the predictions made between DENV and both the human and <i>A. aegypti</i> hosts, both before and after CC filtering. Known Predictions for <i>A. aegypti</i> is listed as NA because we are aware of no known protein-protein interactions between DENV and <i>A. aegypti</i>.</p>", "links"=>[], "tags"=>["predictions"], "article_id"=>469335, "categories"=>["Biochemistry", "Infectious Diseases", "Molecular Biology", "Medicine"], "users"=>["Janet M. Doolittle", "Shawn M. Gomez"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000954.t002", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Interaction_predictions_summary_/469335", "title"=>"Interaction predictions summary.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-02-15 02:35:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/399292", "https://ndownloader.figshare.com/files/399320", "https://ndownloader.figshare.com/files/399346", "https://ndownloader.figshare.com/files/399365", "https://ndownloader.figshare.com/files/399380", "https://ndownloader.figshare.com/files/399390", "https://ndownloader.figshare.com/files/399398", "https://ndownloader.figshare.com/files/399413"], "description"=>"<div><h3>Background</h3><p>Dengue fever is an increasingly significant arthropod-borne viral disease, with at least 50 million cases per year worldwide. As with other viral pathogens, dengue virus is dependent on its host to perform the bulk of functions necessary for viral survival and replication. To be successful, dengue must manipulate host cell biological processes towards its own ends, while avoiding elimination by the immune system. Protein-protein interactions between the virus and its host are one avenue through which dengue can connect and exploit these host cellular pathways and processes.</p><h3>Methodology/Principal Findings</h3><p>We implemented a computational approach to predict interactions between Dengue virus (DENV) and both of its hosts, <em>Homo sapiens</em> and the insect vector <em>Aedes aegypti</em>. Our approach is based on structural similarity between DENV and host proteins and incorporates knowledge from the literature to further support a subset of the predictions. We predict over 4,000 interactions between DENV and humans, as well as 176 interactions between DENV and <em>A. aegypti</em>. Additional filtering based on shared Gene Ontology cellular component annotation reduced the number of predictions to approximately 2,000 for humans and 18 for <em>A. aegypti</em>. Of 19 experimentally validated interactions between DENV and humans extracted from the literature, this method was able to predict nearly half (9). Additional predictions suggest specific interactions between virus and host proteins relevant to interferon signaling, transcriptional regulation, stress, and the unfolded protein response.</p><h3>Conclusions/Significance</h3><p>Dengue virus manipulates cellular processes to its advantage through specific interactions with the host's protein interaction network. The interaction networks presented here provide a set of hypothesis for further experimental investigation into the DENV life cycle as well as potential therapeutic targets.</p></div>", "links"=>[], "tags"=>["interactions", "dengue", "hosts"], "article_id"=>138872, "categories"=>["Biochemistry", "Cancer", "Molecular Biology", "Medicine"], "users"=>["Janet M. Doolittle", "Shawn Gomez"], "doi"=>["https://dx.doi.org/10.1371/journal.pntd.0000954.s001", "https://dx.doi.org/10.1371/journal.pntd.0000954.s002", "https://dx.doi.org/10.1371/journal.pntd.0000954.s003", "https://dx.doi.org/10.1371/journal.pntd.0000954.s004", "https://dx.doi.org/10.1371/journal.pntd.0000954.s005", "https://dx.doi.org/10.1371/journal.pntd.0000954.s006", "https://dx.doi.org/10.1371/journal.pntd.0000954.s007", "https://dx.doi.org/10.1371/journal.pntd.0000954.s008"], "stats"=>{"downloads"=>10, "page_views"=>50, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Mapping_Protein_Interactions_between_Dengue_Virus_and_Its_Human_and_Insect_Hosts/138872", "title"=>"Mapping Protein Interactions between Dengue Virus and Its Human and Insect Hosts", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-02-15 02:27:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/798931"], "description"=>"<p>Experimentally determined nteractions are listed, with the serotype and system that they were demonstrated in.</p>†<p>Interaction suggested in one or more (additional) cell lines by functional assay.</p>‡<p>Interaction suggested for other serotypes by functional assay.</p><p>*Interaction shown to be specific for this serotype.</p>", "links"=>[], "tags"=>["interactions"], "article_id"=>469305, "categories"=>["Biochemistry", "Infectious Diseases", "Molecular Biology", "Medicine"], "users"=>["Janet M. Doolittle", "Shawn M. Gomez"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000954.t001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Known_interactions_between_H_sapiens_and_DENV_/469305", "title"=>"Known interactions between <i>H. sapiens</i> and DENV.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-02-15 02:35:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/798683"], "description"=>"<p>(A) Interferon signaling pathway. IFNA and IFNG bind to their respective receptors and cause the activation of Jak family tyrosine kinases. This activats of STAT proteins, which form hetero- or homodimers and induce the expression of IFN response genes. SOCS proteins negatively regulate JAK1 and PTP proteins negatively regulate JAK1 and STAT1. NS4B can reduce the phosphorylation of STAT1. (B) Predicted interactions between DENV proteins and members of the IFN-induced JAK-STAT pathway.</p>", "links"=>[], "tags"=>["influences", "ifn"], "article_id"=>469054, "categories"=>["Biochemistry", "Infectious Diseases", "Molecular Biology", "Medicine"], "users"=>["Janet M. Doolittle", "Shawn M. Gomez"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000954.g007", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DENV_influences_IFN_signalling_/469054", "title"=>"DENV influences IFN signalling.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-02-15 02:30:54"}

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Relative Metric

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