CODA: Accurate Detection of Functional Associations between Proteins in Eukaryotic Genomes Using Domain Fusion
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{"title"=>"CODA: Accurate detection of functional associations between proteins in eukaryotic genomes using domain fusion", "type"=>"journal", "authors"=>[{"first_name"=>"Adam J.", "last_name"=>"Reid", "scopus_author_id"=>"15760716800"}, {"first_name"=>"Juan A G", "last_name"=>"Ranea", "scopus_author_id"=>"7801487448"}, {"first_name"=>"Andrew B.", "last_name"=>"Clegg", "scopus_author_id"=>"36146926700"}, {"first_name"=>"Christine A.", "last_name"=>"Orengo", "scopus_author_id"=>"7006781333"}], "year"=>2010, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-77956219272", "sgr"=>"77956219272", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0010908", "pmid"=>"20532224", "pui"=>"359289633"}, "id"=>"bdc7055e-c315-3c67-80b1-2f27bdef38ea", "abstract"=>"BACKGROUND: In order to understand how biological systems function it is necessary to determine the interactions and associations between proteins. Gene fusion prediction is one approach to detection of such functional relationships. Its use is however known to be problematic in higher eukaryotic genomes due to the presence of large homologous domain families. Here we introduce CODA (Co-Occurrence of Domains Analysis), a method to predict functional associations based on the gene fusion idiom. METHODOLOGY/PRINCIPAL FINDINGS: We apply a novel scoring scheme which takes account of the genome-specific size of homologous domain families involved in fusion to improve accuracy in predicting functional associations. We show that CODA is able to accurately predict functional similarities in human with comparison to state-of-the-art methods and show that different methods can be complementary. CODA is used to produce evidence that a currently uncharacterised human protein may be involved in pathways related to depression and that another is involved in DNA replication. CONCLUSIONS/SIGNIFICANCE: The relative performance of different gene fusion methodologies has not previously been explored. We find that they are largely complementary, with different methods being more or less appropriate in different genomes. Our method is the only one currently available for download and can be run on an arbitrary dataset by the user. The CODA software and datasets are freely available from ftp://ftp.biochem.ucl.ac.uk/pub/gene3d_data/v6.1.0/CODA/. Predictions are also available via web services from http://funcnet.eu/.", "link"=>"http://www.mendeley.com/research/coda-accurate-detection-functional-associations-between-proteins-eukaryotic-genomes-using-domain-fus", "reader_count"=>19, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>8, "Student > Ph. D. Student"=>3, "Student > Postgraduate"=>1, "Student > Master"=>1, "Student > Bachelor"=>2, "Professor"=>1, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>8, "Student > Ph. D. Student"=>3, "Student > Postgraduate"=>1, "Student > Master"=>1, "Student > Bachelor"=>2, "Professor"=>1, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>7, "Medicine and Dentistry"=>1, "Business, Management and Accounting"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Social Sciences"=>1, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "Computer Science"=>{"Computer Science"=>1}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"United Kingdom"=>3}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/846684"], "description"=>"<p>(a) Relative performance of CODA and STRING-fusion methods on the STRING dataset. (b) Relative performance of CODA and Prolinks-fusion on the Prolinks dataset. (c) Relative performance of CODA and Prolinks-Fusion on the Prolinks dataset, with all results between homologous pairs removed (BLAST E-value <1e-6). (d) Relative performance of CODA and Truong-fusion on the Truong dataset.</p>", "links"=>[], "tags"=>["coda", "methods", "yeast"], "article_id"=>517139, "categories"=>["Molecular Biology", "Biological Sciences", "Medicine", "Genetics"], "users"=>["Adam J. Reid", "Juan A. G. Ranea", "Andrew B. Clegg", "Christine A. Orengo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010908.g002", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparisons_between_CODA_and_other_methods_on_the_yeast_genome_/517139", "title"=>"Comparisons between CODA and other methods on the yeast genome.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-01 01:58:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/846556"], "description"=>"<p>The promiscuity filter removes all results involving a domain that is known to occur in protein chains with 50 or more different domain families, across all genomes. Enrichment is a measure of accuracy: the number of true positives divided by the number of positives expected by chance given the number of hits (see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010908#s4\" target=\"_blank\">methods</a>).</p>", "links"=>[], "tags"=>["promiscuity"], "article_id"=>517012, "categories"=>["Molecular Biology", "Biological Sciences", "Medicine", "Genetics"], "users"=>["Adam J. Reid", "Juan A. G. Ranea", "Andrew B. Clegg", "Christine A. Orengo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010908.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CODA_with_and_without_promiscuity_filter_prom50_/517012", "title"=>"CODA with and without promiscuity filter (prom50).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-01 01:56:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/421511", "https://ndownloader.figshare.com/files/421532", "https://ndownloader.figshare.com/files/421560", "https://ndownloader.figshare.com/files/421577", "https://ndownloader.figshare.com/files/421602", "https://ndownloader.figshare.com/files/421629", "https://ndownloader.figshare.com/files/421657", "https://ndownloader.figshare.com/files/421695", "https://ndownloader.figshare.com/files/421737", "https://ndownloader.figshare.com/files/421764", "https://ndownloader.figshare.com/files/421793"], "description"=>"<div><h3>Background</h3><p>In order to understand how biological systems function it is necessary to determine the interactions and associations between proteins. Gene fusion prediction is one approach to detection of such functional relationships. Its use is however known to be problematic in higher eukaryotic genomes due to the presence of large homologous domain families. Here we introduce CODA (Co-Occurrence of Domains Analysis), a method to predict functional associations based on the gene fusion idiom.</p><h3>Methodology/Principal Findings</h3><p>We apply a novel scoring scheme which takes account of the genome-specific size of homologous domain families involved in fusion to improve accuracy in predicting functional associations. We show that CODA is able to accurately predict functional similarities in human with comparison to state-of-the-art methods and show that different methods can be complementary. CODA is used to produce evidence that a currently uncharacterised human protein may be involved in pathways related to depression and that another is involved in DNA replication.</p><h3>Conclusions/Significance</h3><p>The relative performance of different gene fusion methodologies has not previously been explored. We find that they are largely complementary, with different methods being more or less appropriate in different genomes. Our method is the only one currently available for download and can be run on an arbitrary dataset by the user. The CODA software and datasets are freely available from <a href=\"ftp://ftp.biochem.ucl.ac.uk/pub/gene3d_data/v6.1.0/CODA/\">ftp://ftp.biochem.ucl.ac.uk/pub/gene3d_data/v6.1.0/CODA/</a>. Predictions are also available via web services from <a href=\"http://funcnet.eu/\">http://funcnet.eu/</a>.</p></div>", "links"=>[], "tags"=>["detection", "associations", "proteins", "eukaryotic", "genomes", "fusion"], "article_id"=>143253, "categories"=>["Molecular Biology", "Biological Sciences", "Medicine", "Genetics"], "users"=>["Adam J. Reid", "Juan A. G. Ranea", "Andrew B. Clegg", "Christine A. Orengo"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0010908.s001", "https://dx.doi.org/10.1371/journal.pone.0010908.s002", "https://dx.doi.org/10.1371/journal.pone.0010908.s003", "https://dx.doi.org/10.1371/journal.pone.0010908.s004", "https://dx.doi.org/10.1371/journal.pone.0010908.s005", "https://dx.doi.org/10.1371/journal.pone.0010908.s006", "https://dx.doi.org/10.1371/journal.pone.0010908.s007", "https://dx.doi.org/10.1371/journal.pone.0010908.s008", "https://dx.doi.org/10.1371/journal.pone.0010908.s009", "https://dx.doi.org/10.1371/journal.pone.0010908.s010", "https://dx.doi.org/10.1371/journal.pone.0010908.s011"], "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/CODA_Accurate_Detection_of_Functional_Associations_between_Proteins_in_Eukaryotic_Genomes_Using_Domain_Fusion/143253", "title"=>"CODA: Accurate Detection of Functional Associations between Proteins in Eukaryotic Genomes Using Domain Fusion", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2010-06-01 00:54:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/846849"], "description"=>"<p>(a) Relative performance of CODA and STRING-fusion methods on the STRING dataset. (b) Relative performance of CODA and Prolinks-fusion on the Prolinks dataset.</p>", "links"=>[], "tags"=>["coda", "methods"], "article_id"=>517304, "categories"=>["Molecular Biology", "Biological Sciences", "Medicine", "Genetics"], "users"=>["Adam J. Reid", "Juan A. G. Ranea", "Andrew B. Clegg", "Christine A. Orengo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010908.g004", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparisons_between_CODA_and_other_methods_on_the_human_genome_/517304", "title"=>"Comparisons between CODA and other methods on the human genome.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-01 02:01:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/846910"], "description"=>"<p>Those methods designed purely for examining gene fusion as an evolutionary process have been excluded. ‘All homologues’ refers to the approach of allowing all hits between protein pairs which are homologous to a fusion protein, while ‘orthologue-only’ refers to methods which only allow hits where the query proteins are orthologous to a fusion protein.</p>", "links"=>[], "tags"=>["fusion", "implementations", "predicting"], "article_id"=>517369, "categories"=>["Molecular Biology", "Biological Sciences", "Medicine", "Genetics"], "users"=>["Adam J. Reid", "Juan A. G. Ranea", "Andrew B. Clegg", "Christine A. Orengo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010908.t001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Overview_of_gene_domain_fusion_implementations_for_predicting_functional_associations_/517369", "title"=>"Overview of gene/domain fusion implementations for predicting functional associations.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-06-01 02:02:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/846785"], "description"=>"<p>Overlap in (a) proteins involved in linkages and (b) linked pairs of proteins identified with yeast genome as query. Data is shown for the top scoring 500 hits for CODA and STRING-fusion, the first 1000 hits for CODA and Prolinks-fusion and the first 189 hits for CODA and Truong-fusion. CODA is represented by blue ellipses, STRING-fusion by red and Prolinks-fusion by green and Truong-fusion by orange.</p>", "links"=>[], "tags"=>["Computational biology", "computational biology/macromolecular structure analysis", "genetics and genomics/functional genomics", "molecular biology/bioinformatics", "molecular biology/molecular evolution"], "article_id"=>517243, "categories"=>["Molecular Biology", "Biological Sciences", "Medicine", "Genetics"], "users"=>["Adam J. Reid", "Juan A. G. Ranea", "Andrew B. Clegg", "Christine A. Orengo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010908.g003", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Overlap_between_the_results_of_different_methods_/517243", "title"=>"Overlap between the results of different methods.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-01 02:00:43"}

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