{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T06:31:03Z","timestamp":1756189863157,"version":"3.35.0"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"16","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: Protein\u2013protein interactions are commonly mediated by the physical contact of distinct protein regions. Computational identification of interacting protein regions aids in the detailed understanding of protein networks and supports the prediction of novel protein interactions and the reconstruction of protein complexes.<\/jats:p><jats:p>Results: We introduce an integrative approach for predicting protein region interactions using a probabilistic model fitted to an observed protein network. In particular, we consider globular domains, short linear motifs and coiled-coil regions as potential protein-binding regions. Possible cooperations between multiple regions within the same protein are taken into account. A finegrained confidence system allows for varying the impact of specific protein interactions and region annotations on the modeling process. We apply our prediction approach to a large training set using a maximum likelihood method, compare different scoring functions for region interactions and validate the predicted interactions against a collection of experimentally observed interactions. In addition, we analyze prediction performance with respect to the inclusion of different region types, the incorporation of confidence values for training data and the utilization of predicted protein interactions.<\/jats:p><jats:p>Contact: \u00a0mario.albrecht@mpi-inf.mpg.de<\/jats:p><jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btn290","type":"journal-article","created":{"date-parts":[[2008,8,9]],"date-time":"2008-08-09T13:08:02Z","timestamp":1218287282000},"page":"i35-i41","source":"Crossref","is-referenced-by-count":14,"title":["An integrative approach for predicting interactions of protein regions"],"prefix":"10.1093","volume":"24","author":[{"given":"Sven-Eric","family":"Schelhorn","sequence":"first","affiliation":[{"name":"Max Planck Institute for Informatics, Campus E1.4, 66123 Saarbr\u00fccken, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Lengauer","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Informatics, Campus E1.4, 66123 Saarbr\u00fccken, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Albrecht","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Informatics, Campus E1.4, 66123 Saarbr\u00fccken, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2008,8,9]]},"reference":[{"key":"2023020210502123500_B1","doi-asserted-by":"crossref","first-page":"ii220","DOI":"10.1093\/bioinformatics\/bti1135","article-title":"Decomposing protein networks into domain-domain interactions","volume":"21","author":"Albrecht","year":"2005","journal-title":"Bioinformatics"},{"key":"2023020210502123500_B2","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/nrm1859","article-title":"Structural systems biology: modelling protein interactions","volume":"7","author":"Aloy","year":"2006","journal-title":"Nat. Rev. Mol. Cell Biol"},{"key":"2023020210502123500_B3","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1007\/s00018-007-7451-x","article-title":"The interface of protein-protein complexes: analysis of contacts and prediction of interactions","volume":"65","author":"Bahadur","year":"2007","journal-title":"Cell. Mol. Life Sci"},{"key":"2023020210502123500_B4","doi-asserted-by":"crossref","first-page":"D138","DOI":"10.1093\/nar\/gkh121","article-title":"The Pfam protein families database","volume":"32","author":"Bateman","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"2023020210502123500_B5","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1038\/nsb1203-980","article-title":"Announcing the worldwide Protein Data Bank","volume":"10","author":"Berman","year":"2003","journal-title":"Nat. Struct. Biol"},{"key":"2023020210502123500_B6","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1146\/annurev.biochem.75.103004.142710","article-title":"Domains, motifs, and scaffolds: the role of modular interactions in the evolution and wiring of cell signaling circuits","volume":"75","author":"Bhattacharyya","year":"2006","journal-title":"Annu. Rev. Biochem"},{"key":"2023020210502123500_B7","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1093\/bioinformatics\/17.5.455","article-title":"Predicting protein-protein interactions from primary structure","volume":"17","author":"Bock","year":"2001","journal-title":"Bioinformatics"},{"key":"2023020210502123500_B8","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s00018-004-4416-1","article-title":"The evolution of domain arrangements in proteins and interaction networks","volume":"62","author":"Bornberg-Bauer","year":"2005","journal-title":"Cell. Mol. Life Sci"},{"key":"2023020210502123500_B9","doi-asserted-by":"crossref","first-page":"D557","DOI":"10.1093\/nar\/gkl961","article-title":"DOMINO: a database of domain-peptide interactions","volume":"35","author":"Ceol","year":"2006","journal-title":"Nucleic Acids Res"},{"key":"2023020210502123500_B10","doi-asserted-by":"crossref","first-page":"D572","DOI":"10.1093\/nar\/gkl950","article-title":"MINT: the Molecular INTeraction database","volume":"35","author":"Chatr-aryamontri","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"2023020210502123500_B11","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1002\/prot.20783","article-title":"Inferring protein interactions from experimental data by association probabilistic method","volume":"62","author":"Chen","year":"2006","journal-title":"Proteins"},{"key":"2023020210502123500_B12","doi-asserted-by":"crossref","first-page":"4394","DOI":"10.1093\/bioinformatics\/bti721","article-title":"Prediction of protein-protein interactions using random decision forest framework","volume":"21","author":"Chen","year":"2005","journal-title":"Bioinformatics"},{"key":"2023020210502123500_B13","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1186\/1471-2105-8-401","article-title":"The Protein Identifier Cross-Reference (PICR) service: reconciling protein identifiers across multiple source databases","volume":"8","author":"Cote","year":"2007","journal-title":"BMC Bioinformatics"},{"key":"2023020210502123500_B14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.2517-6161.1977.tb01600.x","article-title":"Maximum likelihood from incomplete data via the EM algorithm","volume":"39","author":"Dempster","year":"1977","journal-title":"J. R. Stat. Soc. Ser. B"},{"key":"2023020210502123500_B15","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1101\/gr.153002","article-title":"Inferring domain-domain interactions from protein-protein interactions","volume":"12","author":"Deng","year":"2002","journal-title":"Genome Res"},{"key":"2023020210502123500_B16","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nrm1589","article-title":"Intrinsically unstructured proteins and their functions","volume":"6","author":"Dyson","year":"2005","journal-title":"Nat. Rev. Mol. Cell Biol"},{"key":"2023020210502123500_B17","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/47056","article-title":"Protein interaction maps for complete genomes based on gene fusion events","volume":"402","author":"Enright","year":"1999","journal-title":"Nature"},{"key":"2023020210502123500_B18","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1093\/bioinformatics\/bti011","article-title":"iPfam: visualization of protein-protein interactions in PDB at domain and amino acid resolutions","volume":"21","author":"Finn","year":"2004","journal-title":"Bioinformatics"},{"key":"2023020210502123500_B19","doi-asserted-by":"crossref","first-page":"D247","DOI":"10.1093\/nar\/gkj149","article-title":"Pfam: clans, web tools and services","volume":"34","author":"Finn","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"2023020210502123500_B20","first-page":"413","article-title":"Towards the prediction of complete protein-protein interaction networks","author":"Gomez","year":"2002","journal-title":"Pac. Symp. Biocomput"},{"key":"2023020210502123500_B21","doi-asserted-by":"crossref","first-page":"R104","DOI":"10.1186\/gb-2006-7-11-r104","article-title":"Predicting domain-domain interactions using a parsimony approach","volume":"7","author":"Guimaraes","year":"2006","journal-title":"Genome Biol"},{"key":"2023020210502123500_B22","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1186\/1471-2105-9-171","article-title":"Interrogating domain-domain interactions with parsimony based approaches","volume":"9","author":"Guimaraes","year":"2008","journal-title":"BMC Bioinformatics"},{"key":"2023020210502123500_B23","first-page":"250","article-title":"A domain combination based probabilistic framework for proteinprotein interaction prediction","volume":"14","author":"Han","year":"2005","journal-title":"Genome Informatics"},{"key":"2023020210502123500_B24","first-page":"56","article-title":"A simple method for inferring strengths of protein-protein interactions","volume":"15","author":"Hayashida","year":"2005","journal-title":"Genome Informatics"},{"key":"2023020210502123500_B25","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/S0968-0004(98)01253-5","article-title":"PQS: a protein quaternary structure file server","volume":"23","author":"Henrick","year":"1998","journal-title":"Trends Biochem. Sci"},{"key":"2023020210502123500_B26","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1109\/TCBB.2007.1001","article-title":"Predicting protein-protein interactions from protein domains using a set cover approach","volume":"4","author":"Huang","year":"2007","journal-title":"IEEE\/ACM Trans. Comput. Biol. Bioinform"},{"key":"2023020210502123500_B27","doi-asserted-by":"crossref","first-page":"E206","DOI":"10.1371\/journal.pbio.0020206","article-title":"Gene duplication: the genomic trade in spare parts","volume":"2","author":"Hurles","year":"2004","journal-title":"PLoS Biol"},{"key":"2023020210502123500_B28","doi-asserted-by":"crossref","first-page":"R125","DOI":"10.1186\/gb-2006-7-12-r125","article-title":"Evolutionary conservation of domain-domain interactions","volume":"7","author":"Itzhaki","year":"2006","journal-title":"Genome Biol"},{"key":"2023020210502123500_B29","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.jmb.2006.07.072","article-title":"Co-evolutionary analysis of domains in interacting proteins reveals insights into domain-domain interactions mediating protein-protein interactions","volume":"362","author":"Jothi","year":"2006","journal-title":"J. Mol. Biol"},{"key":"2023020210502123500_B30","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1002\/prot.21347","article-title":"Predicting protein domain interactions from coevolution of conserved regions","volume":"67","author":"Kann","year":"2007","journal-title":"Proteins"},{"key":"2023020210502123500_B31","doi-asserted-by":"crossref","first-page":"D561","DOI":"10.1093\/nar\/gkl958","article-title":"IntAct - open source resource for molecular interaction data","volume":"35","author":"Kerrien","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"2023020210502123500_B32","first-page":"42","article-title":"Large scale statistical prediction of protein-protein interaction by potentially interacting domain (PID) pair","volume":"13","author":"Kim","year":"2003","journal-title":"Genome Informatics"},{"key":"2023020210502123500_B33","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1186\/1471-2105-7-269","article-title":"An integrated approach to the prediction of domain-domain interactions","volume":"7","author":"Lee","year":"2006","journal-title":"BMC Bioinformatics"},{"key":"2023020210502123500_B34","doi-asserted-by":"crossref","first-page":"3279","DOI":"10.1093\/bioinformatics\/bti492","article-title":"Inferring protein-protein interactions through high-throughput interaction data from diverse organisms","volume":"21","author":"Liu","year":"2005","journal-title":"Bioinformatics"},{"key":"2023020210502123500_B35","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0065-3233(05)70003-6","article-title":"The structure of alpha-helical coiled coils","volume":"70","author":"Lupas","year":"2005","journal-title":"Adv. Protein Chem"},{"key":"2023020210502123500_B36","doi-asserted-by":"crossref","first-page":"W324","DOI":"10.1093\/nar\/gki401","article-title":"BIOVERSE: enhancements to the framework for structural, functional and contextual modeling of proteins and proteomes","volume":"33","author":"McDermott","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"2023020210502123500_B37","doi-asserted-by":"crossref","first-page":"9867","DOI":"10.1073\/pnas.0600220103","article-title":"Long-range cooperative binding effects in a T cell receptor variable domain","volume":"103","author":"Moza","year":"2006","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023020210502123500_B38","doi-asserted-by":"crossref","first-page":"3342","DOI":"10.1016\/j.febslet.2005.04.005","article-title":"Linear motifs: evolutionary interaction switches","volume":"579","author":"Neduva","year":"2005","journal-title":"FEBS Lett"},{"key":"2023020210502123500_B39","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1093\/nar\/gkg079","article-title":"InterDom: a database of putative interacting protein domains for validating predicted protein interactions and complexes","volume":"31","author":"Ng","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"2023020210502123500_B40","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1093\/bioinformatics\/bti086","article-title":"Statistical analysis of domains in interacting protein pairs","volume":"21","author":"Nye","year":"2004","journal-title":"Bioinformatics"},{"key":"2023020210502123500_B41","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1146\/annurev.biochem.74.082803.133029","article-title":"Protein families and their evolution-a structural perspective","volume":"74","author":"Orengo","year":"2005","journal-title":"Annu. Rev. Biochem"},{"key":"2023020210502123500_B42","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1093\/bioinformatics\/btl050","article-title":"The DIMAweb resource \u2013 exploring the protein domain network","volume":"22","author":"Pagel","year":"2006","journal-title":"Bioinformatics"},{"key":"2023020210502123500_B43","doi-asserted-by":"crossref","first-page":"D651","DOI":"10.1093\/nar\/gkm996","article-title":"DIMA 2.0 \u2013 predicted and known domain interactions","volume":"36","author":"Pagel","year":"2008","journal-title":"Nucleic Acids Res"},{"key":"2023020210502123500_B44","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1126\/science.1083653","article-title":"Assembly of cell regulatory systems through protein interaction domains","volume":"300","author":"Pawson","year":"2003","journal-title":"Science"},{"key":"2023020210502123500_B45","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1101\/gr.1680803","article-title":"Development of human protein reference database as an initial platform for approaching systems biology in humans","volume":"13","author":"Peri","year":"2003","journal-title":"Genome Res"},{"key":"2023020210502123500_B46","doi-asserted-by":"crossref","first-page":"3625","DOI":"10.1093\/nar\/gkg545","article-title":"ELM server: a new resource for investigating short functional sites in modular eukaryotic proteins","volume":"31","author":"Puntervoll","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"2023020210502123500_B47","doi-asserted-by":"crossref","first-page":"2541","DOI":"10.1002\/pmic.200600924","article-title":"Computational analysis of human protein interaction networks","volume":"7","author":"Ram\u00edrez","year":"2007","journal-title":"Proteomics"},{"key":"2023020210502123500_B48","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1038\/nbt1103","article-title":"Probabilistic model of the human protein-protein interaction network","volume":"23","author":"Rhodes","year":"2005","journal-title":"Nat. Biotechnol"},{"key":"2023020210502123500_B49","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":"2023020210502123500_B50","doi-asserted-by":"crossref","first-page":"D646","DOI":"10.1093\/nar\/gkm936","article-title":"CORUM: the comprehensive resource of mammalian protein complexes","volume":"36","author":"Ruepp","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"2023020210502123500_B51","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/S1359-6446(05)03513-0","article-title":"Methods to reveal domain networks","volume":"10","author":"Santonico","year":"2005","journal-title":"Drug Discov. Today"},{"key":"2023020210502123500_B52","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1186\/1471-2105-7-302","article-title":"A new measure for functional similarity of gene products based on Gene Ontology","volume":"7","author":"Schlicker","year":"2006","journal-title":"BMC Bioinformatics"},{"key":"2023020210502123500_B53","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1093\/bioinformatics\/btm012","article-title":"Functional evaluation of domain-domain interactions and human protein interaction networks","volume":"23","author":"Schlicker","year":"2007","journal-title":"Bioinformatics"},{"key":"2023020210502123500_B54","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/nrm1960","article-title":"Reading protein modifications with interaction domains","volume":"7","author":"Seet","year":"2006","journal-title":"Nat. Rev. Mol. Cell Biol"},{"key":"2023020210502123500_B55","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1006\/jmbi.2001.4920","article-title":"Correlated sequence-signatures as markers of protein-protein interaction","volume":"311","author":"Sprinzak","year":"2001","journal-title":"J. Mol. Biol"},{"key":"2023020210502123500_B56","doi-asserted-by":"crossref","first-page":"D535","DOI":"10.1093\/nar\/gkj109","article-title":"BioGRID: a general repository for interaction datasets","volume":"34","author":"Stark","year":"2006","journal-title":"Nucleic Acids Res"},{"key":"2023020210502123500_B57","doi-asserted-by":"crossref","first-page":"D413","DOI":"10.1093\/nar\/gki037","article-title":"3did: interacting protein domains of known three-dimensional structure","volume":"33","author":"Stein","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"2023020210502123500_B58","doi-asserted-by":"crossref","first-page":"D262","DOI":"10.1093\/nar\/gki058","article-title":"E-MSD: an integrated data resource for bioinformatics","volume":"33","author":"Velankar","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"2023020210502123500_B59","doi-asserted-by":"crossref","first-page":"R192","DOI":"10.1186\/gb-2007-8-9-r192","article-title":"InSite: a computational method for identifying protein-protein interaction binding sites on a proteome-wide scale","volume":"8","author":"Wang","year":"2007","journal-title":"Genome Biol"},{"key":"2023020210502123500_B60","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1186\/1471-2105-8-391","article-title":"Analysis on multi-domain cooperation for predicting proteinprotein interactions","volume":"8","author":"Wang","year":"2007","journal-title":"BMC Bioinformatics"},{"key":"2023020210502123500_B61","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/1471-2164-7-122","article-title":"Topology and weights in a protein domain interaction network \u2013 a novel way to predict protein interactions","volume":"7","author":"Wuchty","year":"2006","journal-title":"BMC Genomics"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/24\/16\/i35\/49053526\/bioinformatics_24_16_i35.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/24\/16\/i35\/49053526\/bioinformatics_24_16_i35.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T11:20:31Z","timestamp":1738322431000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/24\/16\/i35\/200944"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,8,9]]},"references-count":61,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2008,8,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btn290","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"type":"electronic","value":"1367-4811"},{"type":"print","value":"1367-4803"}],"subject":[],"published-other":{"date-parts":[[2008,8,15]]},"published":{"date-parts":[[2008,8,9]]}}}