{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T02:53:45Z","timestamp":1781664825234,"version":"3.54.5"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Functional linkages implicate pairwise relationships between proteins that work together to implement biological tasks. During evolution, functionally linked proteins are likely to be preserved or eliminated across a range of genomes in a correlated fashion. Based on this hypothesis, phylogenetic profiling-based approaches try to detect pairs of protein families that show similar evolutionary patterns. Traditionally, the evolutionary pattern of a protein is encoded by either a binary profile of presence and absence of this protein across species or an occurrence profile that indicates the distribution of copies of this protein across species.<\/jats:p>\n               <jats:p>Results: In our study, we characterize each protein by its enhanced phylogenetic tree, a novel graphical model of the evolution of a protein family with explicitly marked by speciation and duplication events. By topological comparison between enhanced phylogenetic trees, we are able to detect the functionally associated protein pairs. Because the enhanced phylogenetic trees contain more evolutionary information of proteins, our method shows greater performance and discovers functional linkages among proteins more reliably compared with the conventional approaches.<\/jats:p>\n               <jats:p>Contact: \u00a0xuanhung.ta@helsinki.fi; liisa.holm@helsinki.fi<\/jats:p>\n               <jats:p>Sumplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btq705","type":"journal-article","created":{"date-parts":[[2010,12,18]],"date-time":"2010-12-18T03:20:38Z","timestamp":1292642438000},"page":"700-706","source":"Crossref","is-referenced-by-count":18,"title":["A novel method for assigning functional linkages to proteins using enhanced phylogenetic trees"],"prefix":"10.1093","volume":"27","author":[{"given":"Hung Xuan","family":"Ta","sequence":"first","affiliation":[{"name":"1 Institute of Biotechnology and 2Division of Genetics, Faculty of Biological and Environmental Sciences, PO Box 56, 00014 University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrik","family":"Koskinen","sequence":"additional","affiliation":[{"name":"1 Institute of Biotechnology and 2Division of Genetics, Faculty of Biological and Environmental Sciences, PO Box 56, 00014 University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liisa","family":"Holm","sequence":"additional","affiliation":[{"name":"1 Institute of Biotechnology and 2Division of Genetics, Faculty of Biological and Environmental Sciences, PO Box 56, 00014 University of Helsinki, Helsinki, Finland"},{"name":"1 Institute of Biotechnology and 2Division of Genetics, Faculty of Biological and Environmental Sciences, PO Box 56, 00014 University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,12,17]]},"reference":[{"key":"2023012511564639900_B1","doi-asserted-by":"crossref","first-page":"D115","DOI":"10.1093\/nar\/gkh131","article-title":"UniProt: the Universal Protein knowledgebase","volume":"32","author":"Apweiler","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"2023012511564639900_B2","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. 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Biol."},{"key":"2023012511564639900_B4","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1093\/bioinformatics\/btl558","article-title":"Constrained models of evolution lead to improved prediction of functional linkage from correlated gain and loss of genes","volume":"23","author":"Barker","year":"2007","journal-title":"Bioinformatics"},{"key":"2023012511564639900_B5","doi-asserted-by":"crossref","first-page":"18974","DOI":"10.1074\/jbc.272.30.18974","article-title":"A complex consisting of human replication factor C p40, p37, and p36 subunits is a DNA-dependent ATPase and an intermediate in the assembly of the holoenzyme","volume":"272","author":"Cai","year":"1997","journal-title":"J. Biol. Chem."},{"key":"2023012511564639900_B6","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1074\/mcp.M600381-MCP200","article-title":"Toward a comprehensive atlas of the physical interactome of Saccharomyces cerevisiae","volume":"6","author":"Collins","year":"2007","journal-title":"Mol. Cell. Proteomics"},{"key":"2023012511564639900_B7","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/S0968-0004(98)01274-2","article-title":"Conservation of gene order: a fingerprint of proteins that physically interact","volume":"23","author":"Dandekar","year":"1998","journal-title":"Trends Biochem. Sci."},{"key":"2023012511564639900_B8","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1038\/nbt861","article-title":"Discovery of uncharacterized cellular systems by genome-wide analysis of functional linkages","volume":"21","author":"Date","year":"2003","journal-title":"Nat. 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