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CODA: Accurate Detection of Functional Associations between Proteins in Eukaryotic Genomes Using Domain Fusion

Reid, AJ; Ranea, JAG; Clegg, AB; Orengo, CA; (2010) CODA: Accurate Detection of Functional Associations between Proteins in Eukaryotic Genomes Using Domain Fusion. PLOS ONE , 5 (6) , Article e10908. 10.1371/journal.pone.0010908. Green open access

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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/.

Type: Article
Title: CODA: Accurate Detection of Functional Associations between Proteins in Eukaryotic Genomes Using Domain Fusion
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0010908
Publisher version: http://dx.doi.org/10.1371/journal.pone.0010908
Language: English
Additional information: © 2010 Reid et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. AJR acknowledges financial support from the Biotechnology and Biological Sciences Research Council (http://www.bbsrc.ac.uk/). JAGR acknowledges financial support from the Spanish Education and Science Ministry through the Ramon y Cajal program (RYC-2007-01649) (http://ciencia.micinn.fecyt.es/ciencia/j​sp/plantilla.jsp?area=cajal&id=11), the Plan Nacional project (SAF-09839 Subprograma MED) (http://www.plannacionalidi.es/), and the European Union's ENFIN Network of Excellence (Experimental Network for Functional Integration, LSHG-CT-2005-518254) (http://www.enfin.org/). ABC acknowledges support from the European Union's EMBRACE Network of Excellence (European Model for Bioinformatics Research And Community Education, LHSG-CT-2004-512092) (http://www.embracegrid.info/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: GENE FUSION, SEMANTIC SIMILARITY, ANNOTATION, SEQUENCE, DATABASE, FISSION, EVENTS
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/129843
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