{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T08:29:54Z","timestamp":1681720194244},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Post-translational modifications are vital to the function of proteins, but are hard to study, especially since several modified isoforms of a protein may be present simultaneously. Mass spectrometers are a great tool for investigating modified proteins, but the data they provide is often incomplete, ambiguous and difficult to interpret. Combining data from multiple experimental techniques\u2014especially bottom-up and top-down mass spectrometry\u2014provides complementary information. When integrated with background knowledge this allows a human expert to interpret what modifications are present and where on a protein they are located. However, the process is arduous and for high-throughput applications needs to be automated.<\/jats:p>\n               <jats:p>Results: This article explores a data integration methodology based on Markov chain Monte Carlo and simulated annealing. Our software, the Protein Inference Engine (the PIE) applies these algorithms using a modular approach, allowing multiple types of data to be considered simultaneously and for new data types to be added as needed. Even for complicated data representing multiple modifications and several isoforms, the PIE generates accurate modification predictions, including location. When applied to experimental data collected on the L7\/L12 ribosomal protein the PIE was able to make predictions consistent with manual interpretation for several different L7\/L12 isoforms using a combination of bottom-up data with experimentally identified intact masses.<\/jats:p>\n               <jats:p>Availability: Software, demo projects and source can be downloaded from http:\/\/pie.giddingslab.org\/<\/jats:p>\n               <jats:p>Contact: \u00a0morgan@giddingslab.org.<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online<\/jats:p>","DOI":"10.1093\/bioinformatics\/btr027","type":"journal-article","created":{"date-parts":[[2011,3,9]],"date-time":"2011-03-09T15:42:19Z","timestamp":1299685339000},"page":"844-852","source":"Crossref","is-referenced-by-count":3,"title":["Baking a mass-spectrometry data PIE with McMC and simulated annealing: predicting protein post-translational modifications from integrated top-down and bottom-up data"],"prefix":"10.1093","volume":"27","author":[{"given":"Stuart R.","family":"Jefferys","sequence":"first","affiliation":[{"name":"1 Curriculum in Genetics and Molecular Biology, University of Chapel Hill, Chapel Hill, NC and 2Biomolecular Research Center, Boise State University, Boise, ID 83725, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morgan C.","family":"Giddings","sequence":"additional","affiliation":[{"name":"1 Curriculum in Genetics and Molecular Biology, University of Chapel Hill, Chapel Hill, NC and 2Biomolecular Research Center, Boise State University, Boise, ID 83725, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2011,3,8]]},"reference":[{"key":"2023012511543875000_B1","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1074\/mcp.M900487-MCP200","article-title":"A novel approach for untargeted post-translational modification identification using integer linear optimization and tandem mass spectrometry","volume":"9","author":"Baliban","year":"2010","journal-title":"Mol. Cell Proteomics"},{"key":"2023012511543875000_B2","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/sj.icb.7100098","article-title":"Coordinating TLR-activated signaling pathways in cells of the immune system","volume":"85","author":"Banerjee","year":"2007","journal-title":"Immunol. Cell Biol."},{"key":"2023012511543875000_B3","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.jmb.2004.05.028","article-title":"Improved prediction of signal peptides: SignalP 3.0","volume":"340","author":"Bendtsen","year":"2004","journal-title":"J. Mol. Biol."},{"key":"2023012511543875000_B4","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1006\/jmbi.1999.3310","article-title":"Sequence and structure-based prediction of eukaryotic protein phosphorylation sites","volume":"294","author":"Blom","year":"1999","journal-title":"J. Mol. Biol."},{"key":"2023012511543875000_B5","volume-title":"The Republic of Plato translated, with notes, and an interpretive essay.","author":"Bloom","year":"1991","edition":"2"},{"key":"2023012511543875000_B6","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1002\/mas.20015","article-title":"Proteomics by FTICR mass spectrometry: top down and bottom up","volume":"24","author":"Bogdanov","year":"2005","journal-title":"Mass Spectrom. Rev."},{"key":"2023012511543875000_B7","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/376399a0","article-title":"Conflict over the age of the Universe","volume":"376","author":"Bolte","year":"2002","journal-title":"Nature"},{"key":"2023012511543875000_B8","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1093\/bioinformatics\/bth092","article-title":"TANDEM: matching proteins with tandem mass spectra","volume":"20","author":"Craig","year":"2004","journal-title":"Bioinformatics"},{"key":"2023012511543875000_B9","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1002\/pmic.200300744","article-title":"Unimod: protein modifications for mass spectrometry","volume":"4","author":"Creasy","year":"2004","journal-title":"Proteomics"},{"key":"2023012511543875000_B10","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1126\/science.1124619","article-title":"Mass spectrometry and protein analysis","volume":"312","author":"Domon","year":"2006","journal-title":"Science"},{"key":"2023012511543875000_B11","doi-asserted-by":"crossref","first-page":"3589","DOI":"10.1002\/pmic.201000177","article-title":"Intact mass detection, interpretation, and visualization to automate Top-Down proteomics on a large scale","volume":"10","author":"Durbin","year":"2010","journal-title":"Proteomics"},{"key":"2023012511543875000_B12","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1021\/pr901063t","article-title":"Quantitative analysis of proteome coverage and recovery rates for upstream fractionation methods in proteomics","volume":"9","author":"Fang","year":"2010","journal-title":"J. Proteome Res."},{"key":"2023012511543875000_B13","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1385\/1-59259-890-0:571","article-title":"Protein identification and analysis tools on the ExPASy server","volume-title":"The Proteomics Protocols Handbook.","author":"Gasteiger","year":"2005"},{"key":"2023012511543875000_B14","doi-asserted-by":"crossref","first-page":"8743","DOI":"10.1523\/JNEUROSCI.2294-09.2009","article-title":"Phosphorylation of prion protein at serine 43 induces prion protein conformational change","volume":"29","author":"Giannopoulos","year":"2009","journal-title":"J. Neurosci."},{"key":"2023012511543875000_B15","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1093\/emboj\/cdg007","article-title":"Control of protein life-span by N-terminal methionine excision","volume":"22","author":"Giglione","year":"2003","journal-title":"EMBO J."},{"key":"2023012511543875000_B16","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1146\/annurev.genet.30.1.405","article-title":"Ubiquitin-dependent protein degradation","volume":"30","author":"Hochstrasser","year":"1996","journal-title":"Ann. Rev. Gen."},{"key":"2023012511543875000_B17","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1021\/ac034739d","article-title":"Prediction of posttranslational modifications using intact-protein mass spectrometric data","volume":"76","author":"Holmes","year":"2004","journal-title":"Anal. Chem."},{"key":"2023012511543875000_B18","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S0092-8674(02)00741-9","article-title":"The conformational plasticity of protein kinases","volume":"109","author":"Huse","year":"2002","journal-title":"Cell"},{"key":"2023012511543875000_B19","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.1126\/science.1065889","article-title":"Bayesian inference of phylogeny and its impact on evolutionary biology","volume":"294","author":"Huelsenbeck","year":"2001","journal-title":"Science"},{"key":"2023012511543875000_B20","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/978-1-60761-977-2_17","article-title":"Automated data integration and determination of posttranslational modifications with the protein inference engine","volume-title":"Bioinformatics for Comparative Proteomics.","author":"Jefferys","year":"2011"},{"key":"2023012511543875000_B21","doi-asserted-by":"crossref","first-page":"2987","DOI":"10.1021\/bi902153g","article-title":"Practically useful: what the Rosetta protein modeling suite can do for you","volume":"49","author":"Kaufmann","year":"2010","journal-title":"Biochemistry"},{"key":"2023012511543875000_B22","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1039\/c000896f","article-title":"The emerging process of top down mass spectrometry for protein analysis: biomarkers, protein-therapeutics, and achieving high throughput","volume":"6","author":"Kellie","year":"2010","journal-title":"Mol. BioSyst."},{"key":"2023012511543875000_B23","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1074\/mcp.M800103-MCP200","article-title":"Spectral dictionaries: integrating de novo peptide sequencing with database search of tandem mass spectra","volume":"8","author":"Kim","year":"2009","journal-title":"Mol. Cell Proteomics"},{"key":"2023012511543875000_B24","doi-asserted-by":"crossref","first-page":"196A","DOI":"10.1021\/ac0415657","article-title":"Top-down proteomics","volume":"76","author":"Kelleher","year":"2004","journal-title":"Anal. Chem."},{"key":"2023012511543875000_B25","doi-asserted-by":"crossref","first-page":"8387","DOI":"10.1021\/ac901163c","article-title":"PTMSearchPlus: software tool for automated protein identification and post-translational modification characterization by integrating accurate intact protein mass and bottom-up mass spectrometric data searches","volume":"81","author":"Kertesz","year":"2009","journal-title":"Anal. Chem."},{"key":"2023012511543875000_B26","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1126\/science.220.4598.671","article-title":"Optimization by simulated annealing","volume":"220","author":"Kirkpatrick","year":"1983","journal-title":"Science"},{"key":"2023012511543875000_B27","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s00704-009-0190-1","article-title":"Coverage probability of bootstrap confidence intervals in heavy-tailed frequency models, with application to precipitation data","volume":"101","author":"Kysely","year":"2009","journal-title":"Theor. Appl. Climatol."},{"key":"2023012511543875000_B28","doi-asserted-by":"crossref","first-page":"D622","DOI":"10.1093\/nar\/gkj083","article-title":"dbPTM: an information repository of protein post-translational modification","volume":"34","author":"Lee","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"2023012511543875000_B29","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.aca.2008.06.034","article-title":"Twenty years of interface development for capillary electrophoresis-electrospray ionization-mass spectrometry","volume":"627","author":"Maxwell","year":"2008","journal-title":"Anal. Chim. Acta."},{"key":"2023012511543875000_B30","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1063\/1.1699114","article-title":"Equation of state calculations by fast computing machines","volume":"21","author":"Metropolis","year":"1953","journal-title":"J. Chem. Phys."},{"key":"2023012511543875000_B31","doi-asserted-by":"crossref","first-page":"3341","DOI":"10.1038\/sj.onc.1204458","article-title":"Distinct pattern of p53 phosphorylation in human tumors","volume":"20","author":"Minamoto","year":"2001","journal-title":"Oncogene"},{"key":"2023012511543875000_B32","doi-asserted-by":"crossref","first-page":"4175","DOI":"10.1021\/ac0602266","article-title":"Enhancing electrospray ionization efficiency of peptides by derivatization","volume":"78","author":"Mirzaei","year":"2006","journal-title":"Anal. Chem."},{"key":"2023012511543875000_B33","doi-asserted-by":"crossref","first-page":"3551","DOI":"10.1002\/(SICI)1522-2683(19991201)20:18<3551::AID-ELPS3551>3.0.CO;2-2","article-title":"Probability-based protein identification by searching sequence databases using mass spectrometry data","volume":"20","author":"Perkins","year":"1999","journal-title":"Electrophoresis"},{"key":"2023012511543875000_B34","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1002\/mas.20186","article-title":"Orbitrap mass spectrometry: instrumentation, ion motion and applications","volume":"27","author":"Perry","year":"2008","journal-title":"Mass Spectrom. Rev."},{"key":"2023012511543875000_B35","doi-asserted-by":"crossref","first-page":"472","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":"2023012511543875000_B36","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/nrg2218","article-title":"Histone lysine demethylases: emerging roles in development, physiology and disease","volume":"8","author":"Shi","year":"2007","journal-title":"Nat. Rev. Genet."},{"key":"2023012511543875000_B37","doi-asserted-by":"crossref","first-page":"4626","DOI":"10.1021\/ac050102d","article-title":"InsPecT: Identification of Posttranslationally Modified Peptides from Tandem Mass Spectra","volume":"77","author":"Tanner","year":"2005","journal-title":"Anal. Chem."},{"key":"2023012511543875000_B38","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1021\/ac00104a020","article-title":"Method to correlate tandem mass spectra of modified peptides to amino acid sequences in the protein database","volume":"67","author":"Yates","year":"1995","journal-title":"Anal. Chem."},{"key":"2023012511543875000_B39","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1146\/annurev-bioeng-061008-124934","article-title":"Proteomics by mass spectrometry: approaches, advances, and applications","volume":"11","author":"Yates","year":"2009","journal-title":"Annu. Rev. Biomed. Eng."},{"key":"2023012511543875000_B40","first-page":"562","article-title":"The optimality of naive Bayes","volume-title":"Proceeding of 17th International FLAIRS Conference","author":"Zhang","year":"2004"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/27\/6\/844\/48864728\/bioinformatics_27_6_844.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/27\/6\/844\/48864728\/bioinformatics_27_6_844.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T12:03:51Z","timestamp":1674648231000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/27\/6\/844\/236331"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,3,8]]},"references-count":40,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2011,3,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btr027","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2011,3,15]]},"published":{"date-parts":[[2011,3,8]]}}}