{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T13:24:34Z","timestamp":1760707474732},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2005,3,2]],"date-time":"2005-03-02T00:00:00Z","timestamp":1109721600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2005,3,2]],"date-time":"2005-03-02T00:00:00Z","timestamp":1109721600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Background<\/jats:title>\n                        <jats:p>High-throughput methods identify an overwhelming number of protein-protein interactions. However, the limited accuracy of these methods results in the false identification of many spurious interactions. Accordingly, the resulting interactions are regarded as hypothetical and computational methods are needed to increase their confidence. Several methods have recently been suggested for this purpose including co-expression as a confidence measure for interacting proteins, but their performance is still quite poor.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>We introduce a novel computational method for verification of protein-protein interactions based on the co-expression of orthologs of interacting partners. The performance of our method is analysed using known <jats:italic>S. cerevisiae<\/jats:italic> interactions, and is shown to overcome limitations of previous methods. We present specific examples of known and putative interactions that are detected by our method and not by previous methods, and suggest that they represent transient interactions that might have been conserved and stabilized in other species.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusion<\/jats:title>\n                        <jats:p>Co-expression of orthologous protein-pairs can be used to increase the confidence of hypothetical protein-protein interactions in <jats:italic>S. cerevisiae<\/jats:italic> as well as in other species. This approach may be especially useful for species with no available expression profiles and for transient interactions.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/1471-2105-6-40","type":"journal-article","created":{"date-parts":[[2005,3,3]],"date-time":"2005-03-03T07:25:50Z","timestamp":1109834750000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Computational verification of protein-protein interactions by orthologous co-expression"],"prefix":"10.1186","volume":"6","author":[{"given":"Itay","family":"Tirosh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naama","family":"Barkai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2005,3,2]]},"reference":[{"key":"365_CR1","doi-asserted-by":"publisher","first-page":"4569","DOI":"10.1073\/pnas.061034498","volume":"98","author":"T Ito","year":"2001","unstructured":"Ito T, Chiba T, Ozawa R, Yoshida M, Hattori M, Sakaki Y: A comprehensive two-hybrid analysis to explore the yeast protein interactome. Proc Natl Acad Sci U S A 2001, 98: 4569\u20134574. 10.1073\/pnas.061034498","journal-title":"Proc Natl Acad Sci U S A"},{"key":"365_CR2","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1038\/35001009","volume":"403","author":"P Uetz","year":"2000","unstructured":"Uetz P, Giot L, Cagney G, Mansfield TA, Judson RS, Knight JR, Lockshon D, Narayan V, Srinivasan M, Pochart P, Qureshi-Emili A, Li Y, Godwin B, Conover D, Kalbfleisch T, Vijayadamodar G, Yang M, Johnston M, Fields S, Rothberg JM: A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae. Nature 2000, 403: 623\u2013627. 10.1038\/35001009","journal-title":"Nature"},{"key":"365_CR3","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/415141a","volume":"415","author":"AC Gavin","year":"2002","unstructured":"Gavin AC, Bosche M, Krause R, Grandi P, Marzioch M, Bauer A, Schultz J, Rick JM, Michon AM, Cruciat CM, Remor M, Hofert C, Schelder M, Brajenovic M, Ruffner H, Merino A, Klein K, Hudak M, Dickson D, Rudi T, Gnau V, Bauch A, Bastuck S, Huhse B, Leutwein C, Heurtier MA, Copley RR, Edelmann A, Querfurth E, Rybin V, Drewes G, Raida M, Bouwmeester T, Bork P, Seraphin B, Kuster B, Neubauer G, Superti-Furga G: Functional organization of the yeast proteome by systematic analysis of protein complexes. Nature 2002, 415: 141\u2013147. 10.1038\/415141a","journal-title":"Nature"},{"key":"365_CR4","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1038\/415180a","volume":"415","author":"Y Ho","year":"2002","unstructured":"Ho Y, Gruhler A, Heilbut A, Bader GD, Moore L, Adams SL, Millar A, Taylor P, Bennett K, Boutilier K, Yang L, Wolting C, Donaldson I, Schandorff S, Shewnarane J, Vo M, Taggart J, Goudreault M, Muskat B, Alfarano C, Dewar D, Lin Z, Michalickova K, Willems AR, Sassi H, Nielsen PA, Rasmussen KJ, Andersen JR, Johansen LE, Hansen LH, Jespersen H, Podtelejnikov A, Nielsen E, Crawford J, Poulsen V, Sorensen BD, Matthiesen J, Hendrickson RC, Gleeson F, Pawson T, Moran MF, Durocher D, Mann M, Hogue CW, Figeys D, Tyers M: Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry. Nature 2002, 415: 180\u2013183. 10.1038\/415180a","journal-title":"Nature"},{"key":"365_CR5","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1016\/S0022-2836(03)00239-0","volume":"327","author":"E Sprinzak","year":"2003","unstructured":"Sprinzak E, Sattath S, Margalit H: How reliable are experimental protein-protein interaction data? J Mol Biol 2003, 327: 919\u2013923. 10.1016\/S0022-2836(03)00239-0","journal-title":"J Mol Biol"},{"key":"365_CR6","doi-asserted-by":"publisher","first-page":"1971","DOI":"10.1101\/gr.206701","volume":"11","author":"R Mrowka","year":"2001","unstructured":"Mrowka R, Patzak A, Herzel H: Is there a bias in proteome research? Genome Res 2001, 11: 1971\u20131973. 10.1101\/gr.206701","journal-title":"Genome Res"},{"key":"365_CR7","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/nature750","volume":"417","author":"C von Mering","year":"2002","unstructured":"von Mering C, Krause R, Snel B, Cornell M, Oliver SG, Fields S, Bork P: Comparative assessment of large-scale data sets of protein-protein interactions. Nature 2002, 417: 399\u2013403. 10.1038\/nature750","journal-title":"Nature"},{"key":"365_CR8","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/S0959-440X(03)00070-8","volume":"13","author":"L Salwinski","year":"2003","unstructured":"Salwinski L, Eisenberg D: Computational methods of analysis of protein-protein interactions. Curr Opin Struct Biol 2003, 13: 377\u2013382. 10.1016\/S0959-440X(03)00070-8","journal-title":"Curr Opin Struct Biol"},{"key":"365_CR9","doi-asserted-by":"publisher","first-page":"2120","DOI":"10.1101\/gr.205301","volume":"11","author":"LR Matthews","year":"2001","unstructured":"Matthews LR, Vaglio P, Reboul J, Ge H, Davis BP, Garrels J, Vincent S, Vidal M: Identification of potential interaction networks using sequence-based searches for conserved protein-protein interactions or \"interologs\". Genome Res 2001, 11: 2120\u20132126. 10.1101\/gr.205301","journal-title":"Genome Res"},{"key":"365_CR10","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1074\/mcp.M100037-MCP200","volume":"1","author":"CM Deane","year":"2002","unstructured":"Deane CM, Salwinski L, Xenarios I, Eisenberg D: Protein interactions: two methods for assessment of the reliability of high throughput observations. Mol Cell Proteomics 2002, 1: 349\u2013356. 10.1074\/mcp.M100037-MCP200","journal-title":"Mol Cell Proteomics"},{"key":"365_CR11","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1038\/ng776","volume":"29","author":"H Ge","year":"2001","unstructured":"Ge H, Liu Z, Church GM, Vidal M: Correlation between transcriptome and interactome mapping data from Saccharomyces cerevisiae. Nat Genet 2001, 29: 482\u2013486. 10.1038\/ng776","journal-title":"Nat Genet"},{"key":"365_CR12","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1101\/gr.205602","volume":"12","author":"R Jansen","year":"2002","unstructured":"Jansen R, Greenbaum D, Gerstein M: Relating whole-genome expression data with protein-protein interactions. Genome Res 2002, 12: 37\u201346. 10.1101\/gr.205602","journal-title":"Genome Res"},{"key":"365_CR13","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1016\/S1097-2765(02)00531-2","volume":"9","author":"P Kemmeren","year":"2002","unstructured":"Kemmeren P, van Berkum NL, Vilo J, Bijma T, Donders R, Brazma A, Holstege FC: Protein interaction verification and functional annotation by integrated analysis of genome-scale data. Mol Cell 2002, 9: 1133\u20131143. 10.1016\/S1097-2765(02)00531-2","journal-title":"Mol Cell"},{"key":"365_CR14","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1093\/nar\/30.1.31","volume":"30","author":"HW Mewes","year":"2002","unstructured":"Mewes HW, Frishman D, Guldener U, Mannhaupt G, Mayer K, Mokrejs M, Morgenstern B, Munsterkotter M, Rudd S, Weil B: MIPS: a database for genomes and protein sequences. Nucleic Acids Res 2002, 30: 31\u201334. 10.1093\/nar\/30.1.31","journal-title":"Nucleic Acids Res"},{"key":"365_CR15","doi-asserted-by":"publisher","first-page":"1727","DOI":"10.1126\/science.1090289","volume":"302","author":"L Giot","year":"2003","unstructured":"Giot L, Bader JS, Brouwer C, Chaudhuri A, Kuang B, Li Y, Hao YL, Ooi CE, Godwin B, Vitols E, Vijayadamodar G, Pochart P, Machineni H, Welsh M, Kong Y, Zerhusen B, Malcolm R, Varrone Z, Collis A, Minto M, Burgess S, McDaniel L, Stimpson E, Spriggs F, Williams J, Neurath K, Ioime N, Agee M, Voss E, Furtak K, Renzulli R, Aanensen N, Carrolla S, Bickelhaupt E, Lazovatsky Y, DaSilva A, Zhong J, Stanyon CA, Finley RLJ, White KP, Braverman M, Jarvie T, Gold S, Leach M, Knight J, Shimkets RA, McKenna MP, Chant J, Rothberg JM: A protein interaction map of Drosophila melanogaster. Science 2003, 302: 1727\u20131736. 10.1126\/science.1090289","journal-title":"Science"},{"key":"365_CR16","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1126\/science.1091403","volume":"303","author":"S Li","year":"2004","unstructured":"Li S, Armstrong CM, Bertin N, Ge H, Milstein S, Boxem M, Vidalain PO, Han JD, Chesneau A, Hao T, Goldberg DS, Li N, Martinez M, Rual JF, Lamesch P, Xu L, Tewari M, Wong SL, Zhang LV, Berriz GF, Jacotot L, Vaglio P, Reboul J, Hirozane-Kishikawa T, Li Q, Gabel HW, Elewa A, Baumgartner B, Rose DJ, Yu H, Bosak S, Sequerra R, Fraser A, Mango SE, Saxton WM, Strome S, Van Den Heuvel S, Piano F, Vandenhaute J, Sardet C, Gerstein M, Doucette-Stamm L, Gunsalus KC, Harper JW, Cusick ME, Roth FP, Hill DE, Vidal M: A map of the interactome network of the metazoan C. elegans. Science 2004, 303: 540\u2013543. 10.1126\/science.1091403","journal-title":"Science"},{"key":"365_CR17","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1006\/jmbi.2000.3732","volume":"299","author":"CS Goh","year":"2000","unstructured":"Goh CS, Bogan AA, Joachimiak M, Walther D, Cohen FE: Co-evolution of proteins with their interaction partners. Journal of Molecular Biology 2000, 299: 283\u2013293. 10.1006\/jmbi.2000.3732","journal-title":"Journal of Molecular Biology"},{"key":"365_CR18","doi-asserted-by":"publisher","first-page":"W69","DOI":"10.1093\/nar\/gkh471","volume":"32","author":"SH Tan","year":"2004","unstructured":"Tan SH, Zhang Z, Ng SK: ADVICE: Automated Detection and Validation of Interaction by Co-Evolution. Nucleic Acids Res 2004, 32: W69\u201372. 10.1093\/nar\/gnh072","journal-title":"Nucleic Acids Res"},{"key":"365_CR19","doi-asserted-by":"publisher","first-page":"E9","DOI":"10.1371\/journal.pbio.0020009","volume":"2","author":"S Bergmann","year":"2004","unstructured":"Bergmann S, Ihmels J, Barkai N: Similarities and differences in genome-wide expression data of six organisms. PLoS Biol 2004, 2: E9. 10.1371\/journal.pbio.0020009","journal-title":"PLoS Biol"},{"key":"365_CR20","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1126\/science.1087447","volume":"302","author":"JM Stuart","year":"2003","unstructured":"Stuart JM, Segal E, Koller D, Kim SK: A gene-coexpression network for global discovery of conserved genetic modules. Science 2003, 302: 249\u2013255. 10.1126\/science.1087447","journal-title":"Science"},{"key":"365_CR21","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.tig.2003.12.007","volume":"20","author":"P Pagel","year":"2004","unstructured":"Pagel P, Mewes HW, Frishman D: Conservation of protein-protein interactions - lessons from ascomycota. Trends Genet 2004, 20: 72\u201376. 10.1016\/j.tig.2003.12.007","journal-title":"Trends Genet"},{"key":"365_CR22","doi-asserted-by":"publisher","first-page":"3389","DOI":"10.1093\/nar\/25.17.3389","volume":"25","author":"SF Altschul","year":"1997","unstructured":"Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ: Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 1997, 25: 3389\u20133402. 10.1093\/nar\/25.17.3389","journal-title":"Nucleic Acids Res"},{"key":"365_CR23","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1093\/oxfordjournals.molbev.a026387","volume":"17","author":"J Liu","year":"2000","unstructured":"Liu J, Kipreos ET: Evolution of cyclin-dependent kinases (CDKs) and CDK-activating kinases (CAKs): differential conservation of CAKs in yeast and metazoa. Mol Biol Evol 2000, 17: 1061\u20131074.","journal-title":"Mol Biol Evol"},{"key":"365_CR24","doi-asserted-by":"publisher","first-page":"7331","DOI":"10.1128\/MCB.21.21.7331-7344.2001","volume":"21","author":"RJ Durso","year":"2001","unstructured":"Durso RJ, Fisher AK, Albright-Frey TJ, Reese JC: Analysis of TAF90 mutants displaying allele-specific and broad defects in transcription. Mol Cell Biol 2001, 21: 7331\u20137344. 10.1128\/MCB.21.21.7331-7344.2001","journal-title":"Mol Cell Biol"},{"key":"365_CR25","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/S0092-8674(00)81219-2","volume":"94","author":"VV Ogryzko","year":"1998","unstructured":"Ogryzko VV, Kotani T, Zhang X, Schiltz RL, Howard T, Yang XJ, Howard BH, Qin J, Nakatani Y: Histone-like TAFs within the PCAF histone acetylase complex. Cell 1998, 94: 35\u201344. 10.1016\/S0092-8674(00)81219-2","journal-title":"Cell"},{"key":"365_CR26","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1002\/(SICI)1097-0061(19990330)15:5<397::AID-YEA384>3.0.CO;2-U","volume":"15","author":"B Reimann","year":"1999","unstructured":"Reimann B, Bradsher J, Franke J, Hartmann E, Wiedmann M, Prehn S, Wiedmann B: Initial characterization of the nascent polypeptide-associated complex in yeast. Yeast 1999, 15: 397\u2013407. 10.1002\/(SICI)1097-0061(19990330)15:5<397::AID-YEA384>3.3.CO;2-L","journal-title":"Yeast"},{"key":"365_CR27","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1038\/35056591","volume":"2","author":"S Muller","year":"2001","unstructured":"Muller S, Hoege C, Pyrowolakis G, Jentsch S: SUMO, ubiquitin's mysterious cousin. Nat Rev Mol Cell Biol 2001, 2: 202\u2013210. 10.1038\/35056591","journal-title":"Nat Rev Mol Cell Biol"},{"key":"365_CR28","doi-asserted-by":"publisher","first-page":"9033","DOI":"10.1073\/pnas.0402591101","volume":"101","author":"HB Fraser","year":"2004","unstructured":"Fraser HB, Hirsh AE, Wall DP, Eisen MB: Coevolution of gene expression among interacting proteins. Proc Natl Acad Sci U S A 2004, 101: 9033\u20139038. 10.1073\/pnas.0402591101","journal-title":"Proc Natl Acad Sci U S A"},{"key":"365_CR29","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/1471-2105-5-38","volume":"5","author":"LV Zhang","year":"2004","unstructured":"Zhang LV, Wong SL, King OD, Roth FP: Predicting co-complexed protein pairs using genomic and proteomic data integration. BMC Bioinformatics 2004, 5: 38. 10.1186\/1471-2105-5-38","journal-title":"BMC Bioinformatics"},{"key":"365_CR30","unstructured":"Barkai's lab home page[http:\/\/www.weizmann.ac.il\/home\/barkai]"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2105-6-40.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/1471-2105-6-40\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2105-6-40.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T12:06:35Z","timestamp":1728302795000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/1471-2105-6-40"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,3,2]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2005,12]]}},"alternative-id":["365"],"URL":"https:\/\/doi.org\/10.1186\/1471-2105-6-40","relation":{},"ISSN":["1471-2105"],"issn-type":[{"type":"electronic","value":"1471-2105"}],"subject":[],"published":{"date-parts":[[2005,3,2]]},"assertion":[{"value":"8 September 2004","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 March 2005","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 March 2005","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"40"}}