{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T20:50:22Z","timestamp":1774039822383,"version":"3.50.1"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":2846,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/2.0\/uk\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: Yeast two-hybrid screens are an important method to map pairwise protein interactions. This method can generate spurious interactions (false discoveries), and true interactions can be missed (false negatives). Previously, we reported a capture\u2013recapture estimator for bait-specific precision and recall. Here, we present an improved method that better accounts for heterogeneity in bait-specific error rates.<\/jats:p><jats:p>Result: For yeast, worm and fly screens, we estimate the overall false discovery rates (FDRs) to be 9.9%, 13.2% and 17.0% and the false negative rates (FNRs) to be 51%, 42% and 28%. Bait-specific FDRs and the estimated protein degrees are then used to identify protein categories that yield more (or fewer) false positive interactions and more (or fewer) interaction partners. While membrane proteins have been suggested to have elevated FDRs, the current analysis suggests that intrinsic membrane proteins may actually have reduced FDRs. Hydrophobicity is positively correlated with decreased error rates and fewer interaction partners. These methods will be useful for future two-hybrid screens, which could use ultra-high-throughput sequencing for deeper sampling of interacting bait\u2013prey pairs.<\/jats:p><jats:p>Availability: All software (C source) and datasets are available as supplemental files and at http:\/\/www.baderzone.org under the Lesser GPL v. 3 license.<\/jats:p><jats:p>Contact: \u00a0joel.bader@jhu.edu<\/jats:p><jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btn640","type":"journal-article","created":{"date-parts":[[2008,12,18]],"date-time":"2008-12-18T01:25:09Z","timestamp":1229563509000},"page":"372-378","source":"Crossref","is-referenced-by-count":63,"title":["Precision and recall estimates for two-hybrid screens"],"prefix":"10.1093","volume":"25","author":[{"given":"Hailiang","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering and High-Throughput Biology Center, Johns Hopkins University, Baltimore, MD, USA"}]},{"given":"Joel S.","family":"Bader","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and High-Throughput Biology Center, Johns Hopkins University, Baltimore, MD, USA"}]}],"member":"286","published-online":{"date-parts":[[2008,12,17]]},"reference":[{"key":"2023013110025178000_B1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology. The Gene Ontology Consortium","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. Genet."},{"key":"2023013110025178000_B2","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1126\/science.1123221","article-title":"Systems biology. When proteomes collide","volume":"311","author":"Bader","year":"2006","journal-title":"Science"},{"key":"2023013110025178000_B3","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":"2023013110025178000_B4","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/0022-2836(87)90189-6","article-title":"Hydrophobicity scales and computational techniques for detecting amphipathic structures in proteins","volume":"195","author":"Cornette","year":"1987","journal-title":"J. Mol. Biol."},{"key":"2023013110025178000_B5","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1074\/mcp.M100037-MCP200","article-title":"Protein interactions: two methods for assessment of the reliability of high throughput observations","volume":"1","author":"Deane","year":"2002","journal-title":"Mol. Cell Proteomics"},{"key":"2023013110025178000_B6","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. B"},{"key":"2023013110025178000_B7","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S0168-9525(02)02763-4","article-title":"Bridging structural biology and genomics: assessing protein interaction data with known complexes","volume":"18","author":"Edwards","year":"2002","journal-title":"Trends Genet."},{"key":"2023013110025178000_B8","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1038\/nature06199","article-title":"Revisiting Levy flight search patterns of wandering albatrosses, bumblebees and deer","volume":"449","author":"Edwards","year":"2007","journal-title":"Nature"},{"key":"2023013110025178000_B9","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/0022-2836(84)90309-7","article-title":"Analysis of membrane and surface protein sequences with the hydrophobic moment plot","volume":"179","author":"Eisenberg","year":"1984","journal-title":"J. Mol. Biol."},{"key":"2023013110025178000_B10","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1093\/bioinformatics\/btg469","article-title":"A statistical framework for combining and interpreting proteomic datasets","volume":"20","author":"Gilchrist","year":"2004","journal-title":"Bioinformatics"},{"key":"2023013110025178000_B11","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1126\/science.1090289","article-title":"A protein interaction map of Drosophila melanogaster","volume":"302","author":"Giot","year":"2003","journal-title":"Science"},{"key":"2023013110025178000_B12","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1186\/gb-2006-7-11-120","article-title":"How complete are current yeast and human protein-interaction networks?","volume":"7","author":"Hart","year":"2006","journal-title":"Genome Biol."},{"key":"2023013110025178000_B13","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/nmeth.1179","article-title":"Whole-genome sequencing and variant discovery in C. elegans","volume":"5","author":"Hillier","year":"2008","journal-title":"Nat. Methods"},{"key":"2023013110025178000_B14","doi-asserted-by":"crossref","first-page":"e214","DOI":"10.1371\/journal.pcbi.0030214","article-title":"Where have all the interactions gone? Estimating the coverage of two-hybrid protein interaction maps","volume":"3","author":"Huang","year":"2007","journal-title":"PLoS Comput. Biol."},{"key":"2023013110025178000_B15","doi-asserted-by":"crossref","first-page":"4569","DOI":"10.1073\/pnas.061034498","article-title":"A comprehensive two-hybrid analysis to explore the yeast protein interactome","volume":"98","author":"Ito","year":"2001","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023013110025178000_B16","doi-asserted-by":"crossref","first-page":"10340","DOI":"10.1073\/pnas.91.22.10340","article-title":"Split ubiquitin as a sensor of protein interactions in vivo","volume":"91","author":"Johnsson","year":"1994","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023013110025178000_B17","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1093\/biomet\/52.1-2.225","article-title":"Explicit estimates from capture-recapture data with both death and immigration-stochastic model","volume":"52","author":"Jolly","year":"1965","journal-title":"Biometrika"},{"key":"2023013110025178000_B18","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1006\/jmbi.2000.4315","article-title":"Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes","volume":"305","author":"Krogh","year":"2001","journal-title":"J. Mol. Biol."},{"key":"2023013110025178000_B19","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/0022-2836(82)90515-0","article-title":"A simple method for displaying the hydropathic character of a protein","volume":"157","author":"Kyte","year":"1982","journal-title":"J. Mol. Biol."},{"key":"2023013110025178000_B20","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1126\/science.1091403","article-title":"A map of the interactome network of the metazoan C. elegans","volume":"303","author":"Li","year":"2004","journal-title":"Science"},{"key":"2023013110025178000_B21","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/nature03959","article-title":"Genome sequencing in microfabricated high-density picolitre reactors","volume":"437","author":"Margulies","year":"2005","journal-title":"Nature"},{"key":"2023013110025178000_B22","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1126\/science.4023714","article-title":"Hydrophobicity of amino acid residues in globular proteins","volume":"229","author":"Rose","year":"1985","journal-title":"Science"},{"key":"2023013110025178000_B23","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1038\/nature04209","article-title":"Towards a proteome-scale map of the human protein\u2013protein interaction network","volume":"437","author":"Rual","year":"2005","journal-title":"Nature"},{"key":"2023013110025178000_B24","doi-asserted-by":"crossref","first-page":"D449","DOI":"10.1093\/nar\/gkh086","article-title":"The Database of Interacting Proteins: 2004 update","volume":"32","author":"Salwinski","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"2023013110025178000_B25","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1093\/bioinformatics\/btm565","article-title":"Estimating node degree in bait-prey graphs","volume":"24","author":"Scholtens","year":"2008","journal-title":"Bioinformatics"},{"key":"2023013110025178000_B26","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1093\/biomet\/52.1-2.249","article-title":"A note on the multiple-recapture census","volume":"52","author":"Seber","year":"1965","journal-title":"Biometrika"},{"key":"2023013110025178000_B27","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/S0022-2836(03)00239-0","article-title":"How reliable are experimental protein\u2013protein interaction data?","volume":"327","author":"Sprinzak","year":"2003","journal-title":"J. Mol. Biol."},{"key":"2023013110025178000_B28","doi-asserted-by":"crossref","first-page":"5187","DOI":"10.1073\/pnas.95.9.5187","article-title":"A genetic system based on split-ubiquitin for the analysis of interactions between membrane proteins in vivo","volume":"95","author":"Stagljar","year":"1998","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023013110025178000_B29","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/j.cell.2005.08.029","article-title":"A human protein-protein interaction network: a resource for annotating the proteome","volume":"122","author":"Stelzl","year":"2005","journal-title":"Cell"},{"key":"2023013110025178000_B30","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1126\/science.1153878","article-title":"An in vivo map of the yeast protein interactome","volume":"320","author":"Tarassov","year":"2008","journal-title":"Science"},{"key":"2023013110025178000_B31","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1093\/bioinformatics\/btn001","article-title":"Interpool: interpreting smart-pooling results","volume":"24","author":"Thierry-Mieg","year":"2008","journal-title":"Bioinformatics"},{"key":"2023013110025178000_B32","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1126\/science.1116804","article-title":"Herpesviral protein networks and their interaction with the human proteome","volume":"311","author":"Uetz","year":"2006","journal-title":"Science"},{"key":"2023013110025178000_B33","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":"2023013110025178000_B34","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1101\/gr.076463.108","article-title":"A high-resolution, nucleosome position map of C. elegans reveals a lack of universal sequence-dictated positioning","volume":"18","author":"Valouev","year":"2008","journal-title":"Genome Res."},{"key":"2023013110025178000_B35","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/381413a0","article-title":"Levy flight search patterns of wandering albatrosses","volume":"381","author":"Viswanathan","year":"1996","journal-title":"Nature"},{"key":"2023013110025178000_B36","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/nature750","article-title":"Comparative assessment of large-scale data sets of protein\u2013protein interactions","volume":"417","author":"von Mering","year":"2002","journal-title":"Nature"},{"key":"2023013110025178000_B37","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1126\/science.1158684","article-title":"High-quality binary protein interaction map of the yeast interactome network","volume":"322","author":"Yu","year":"2008","journal-title":"Science"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/25\/3\/372\/48982355\/bioinformatics_25_3_372.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/25\/3\/372\/48982355\/bioinformatics_25_3_372.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T07:18:58Z","timestamp":1738826338000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/25\/3\/372\/244556"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,12,17]]},"references-count":37,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2009,2,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btn640","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2009,2,1]]},"published":{"date-parts":[[2008,12,17]]}}}