{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:04:36Z","timestamp":1787317476023,"version":"build-2736575974"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"16","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Motivation: Protein\u2013protein interaction networks are one of the major post-genomic data sources available to molecular biologists. They provide a comprehensive view of the global interaction structure of an organism's proteome, as well as detailed information on specific interactions. Here we suggest a physical model of protein interactions that can be used to extract additional information at an intermediate level: It enables us to identify proteins which share biological interaction motifs, and also to identify potentially missing or spurious interactions.<\/jats:p>\n                  <jats:p>Results: Our new graph model explains observed interactions between proteins by an underlying interaction of complementary binding domains (lock-and-key model). This leads to a novel graph-theoretical algorithm to identify bipartite subgraphs within protein\u2013protein interaction networks where the underlying data are taken from yeast two-hybrid experimental results. By testing on synthetic data, we demonstrate that under certain modelling assumptions, the algorithm will return correct domain information about each protein in the network. Tests on data from various model organisms show that the local and global patterns predicted by the model are indeed found in experimental data. Using functional and protein structure annotations, we show that bipartite subnetworks can be identified that correspond to biologically relevant interaction motifs. Some of these are novel and we discuss an example involving SH3 domains from the Saccharomyces cerevisiae interactome.<\/jats:p>\n                  <jats:p>Availability: The algorithm (in Matlab format) is available (see )<\/jats:p>\n                  <jats:p>Contact: jmorriso@dcs.gla.ac.uk<\/jats:p>\n                  <jats:p>Supplementary information: Supplementary data are available at .<\/jats:p>","DOI":"10.1093\/bioinformatics\/btl338","type":"journal-article","created":{"date-parts":[[2006,6,20]],"date-time":"2006-06-20T23:47:02Z","timestamp":1150847222000},"page":"2012-2019","source":"Crossref","is-referenced-by-count":83,"title":["A lock-and-key model for protein\u2013protein interactions"],"prefix":"10.1093","volume":"22","author":[{"given":"Julie L.","family":"Morrison","sequence":"first","affiliation":[{"name":"Bioinformatics Research Centre, Department of Computing Science, University of Glasgow 1 \u00a0 1 \u00a0 \u00a0 G12 8QQ, UK"},{"name":"Department of Mathematics, University of Strathclyde 2 \u00a0 2 \u00a0 \u00a0 G1 1XH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Breitling","sequence":"additional","affiliation":[{"name":"Groningen Bioinformatics Centre, University of Groningen 3 \u00a0 3 \u00a0 \u00a0 Kerklaan 30, 9751 NN Haren, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desmond J.","family":"Higham","sequence":"additional","affiliation":[{"name":"Department of Mathematics, University of Strathclyde 2 \u00a0 2 \u00a0 \u00a0 G1 1XH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Bioinformatics Research Centre, Department of Computing Science, University of Glasgow 1 \u00a0 1 \u00a0 \u00a0 G12 8QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2006,6,20]]},"reference":[{"key":"2023012409101836100_b1","first-page":"D418","article-title":"The Biomolecular Interaction Network Database and related tools 2005 update","volume":"1","author":"Alfarano","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"2023012409101836100_b2","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1093\/bioinformatics\/bti021","article-title":"Iterative cluster analysis of protein interaction data","volume":"21","author":"Arnau","year":"2001","journal-title":"Bioinformatics"},{"key":"2023012409101836100_b3","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/nbt924","article-title":"Gaining confidence in high-throughput protein interactions","volume":"22","author":"Bader","year":"2004","journal-title":"Nat. Biotechnol."},{"key":"2023012409101836100_b4","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/0022-2496(75)90001-2","article-title":"The area above the ordinal dominance graph and the area below the receiver operating characteristic graph","volume":"12","author":"Bamber","year":"1975","journal-title":"J. Math. Psychol."},{"key":"2023012409101836100_b5","doi-asserted-by":"crossref","first-page":"D138","DOI":"10.1093\/nar\/gkh121","article-title":"The Pfam protein families database","volume":"32","author":"Bateman","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"2023012409101836100_b6","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/1471-2105-5-34","article-title":"Iterative Group Analysis (iGA): a simple tool to enhance sensitivity and facilitate interpretation of microarray experiments","volume":"5","author":"Breitling","year":"2004","journal-title":"BMC Bioinformatics"},{"key":"2023012409101836100_b7","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.sbi.2004.05.003","article-title":"Protein interaction networks from yeast to human","volume":"14","author":"Bork","year":"2004","journal-title":"Curr. Opin. Struct. Biol."},{"key":"2023012409101836100_b8","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1083\/jcb.200104057","article-title":"A protein interaction map for cell polarity development","volume":"154","author":"Drees","year":"2001","journal-title":"J. Cell boil."},{"key":"2023012409101836100_b9","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S0168-9525(02)02763-4","article-title":"Bridging structural biology and genomics: assessing protein\u2013protein interaction datasets","volume":"18","author":"Edwards","year":"2002","journal-title":"Trends Genet."},{"key":"2023012409101836100_b10","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1534\/genetics.104.040063","article-title":"Interaction of Saccharomyces cerevisiae cortical actin patch protein Rvs167p with proteins involved in ER to Golgi vesicle trafficking","volume":"170","author":"Friesen","year":"2005","journal-title":"Genetics"},{"key":"2023012409101836100_b11","volume-title":"Matrix Computations","author":"Golub","year":"1996"},{"key":"2023012409101836100_b12","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0097-8485(96)80004-0","article-title":"Use of receiver operating characteristic (ROC) analysis to evaluate sequence matching","volume":"20","author":"Gribskov","year":"1996","journal-title":"Comput. Chem."},{"key":"2023012409101836100_b13","doi-asserted-by":"crossref","first-page":"4569","DOI":"10.1073\/pnas.061034498","article-title":"A comprehensive two-hybrid analysis to explore the yeast protein interaction interactome","volume":"98","author":"Ito","year":"2001","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012409101836100_b14","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/35036627","article-title":"The large-scale organization of metabolic networks","volume":"507","author":"Jeong","year":"2000","journal-title":"Nature"},{"key":"2023012409101836100_b15","doi-asserted-by":"crossref","first-page":"3077","DOI":"10.1242\/jcs.01290","article-title":"The syndapin protein family: linking membrane trafficking with the cytoskeleton","volume":"17","author":"Kessels","year":"2004","journal-title":"J. Cell Sci."},{"key":"2023012409101836100_b16","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1089\/cmb.2006.13.810","article-title":"How scale-free are gene-networks?","volume":"13","author":"Khanin","year":"2006","journal-title":"J. Comput. Biol."},{"key":"2023012409101836100_b17","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1242\/jcs.114.7.1253","article-title":"SH3 domains: complexity in moderation","volume":"114","author":"Mayer","year":"2001","journal-title":"J. Cell Sci."},{"key":"2023012409101836100_b18","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.1101\/gad.274403","article-title":"Unique Sm core structure of U7 snRNPs: assembly by a specialized SMN complex and the role of a new component, Lsm11, in histone RNA processing","volume":"17","author":"Pillai","year":"2003","journal-title":"Genes Dev."},{"key":"2023012409101836100_b19","first-page":"3808","article-title":"Modeling interactome: scale-free or geometric?","volume":"20","author":"Prulj,N. et al.","year":"2004","journal-title":"Bioinformatics"},{"key":"2023012409101836100_b20","doi-asserted-by":"crossref","first-page":"R89","DOI":"10.1186\/gb-2005-6-10-r89","article-title":"Inferring protein domain interactions from databases of interacting proteins","volume":"6","author":"Riley","year":"2005","journal-title":"Genome Biol."},{"key":"2023012409101836100_b21","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/S0959-440X(03)00070-8","article-title":"Computational methods of analysis of protein\u2013protein interactions","volume":"13","author":"Salwinski","year":"2003","journal-title":"Curr. Opin. Struct. Biol."},{"key":"2023012409101836100_b22","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1042\/bst0311491","article-title":"On the structure of protein\u2013protein interaction networks","volume":"31","author":"Thomas","year":"2003","journal-title":"Biochem. Soc. Trans."},{"key":"2023012409101836100_b23","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/35001009","article-title":"A comprehensive analysis of protein\u2013protein interactions in Saccharomyces cerevisiae","volume":"403","author":"Uetz","year":"2000","journal-title":"Nature"},{"key":"2023012409101836100_b24","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/nature750","article-title":"Comparative assessment of large-scale datasets of protein\u2013protein interactions","volume":"417","author":"von Mering","year":"2002","journal-title":"Nature"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/22\/16\/2012\/48838808\/bioinformatics_22_16_2012.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/22\/16\/2012\/48838808\/bioinformatics_22_16_2012.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T04:43:29Z","timestamp":1674535409000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/22\/16\/2012\/208679"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,6,20]]},"references-count":24,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2006,8,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btl338","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2006,8,15]]},"published":{"date-parts":[[2006,6,20]]}}}