{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T03:38:09Z","timestamp":1776397089385,"version":"3.51.2"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"15","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: Proteins play a crucial role in biological activity, so much can be learned from measuring protein expression and post-translational modification quantitatively. The reverse-phase protein lysate arrays allow us to quantify the relative expression levels of a protein in many different cellular samples simultaneously. Existing approaches to quantify protein arrays use parametric response curves fit to dilution series data. The results can be biased when the parametric function does not fit the data.<\/jats:p><jats:p>Results: We propose a non-parametric approach which adapts to any monotone response curve. The non-parametric approach is shown to be promising via both simulation and real data studies; it reduces the bias due to model misspecification and protects against outliers in the data. The non-parametric approach enables more reliable quantification of protein lysate arrays.<\/jats:p><jats:p>Availability: Code to implement the proposed method in the statistical package R is available at: http:\/\/odin.mdacc.tmc.edu\/jhu\/lysatearray-analysis\/<\/jats:p><jats:p>Contact: \u00a0jhu@mdanderson.org<\/jats:p><jats:p>Supplementary information: Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btm283","type":"journal-article","created":{"date-parts":[[2007,6,29]],"date-time":"2007-06-29T00:25:06Z","timestamp":1183076706000},"page":"1986-1994","source":"Crossref","is-referenced-by-count":199,"title":["Non-parametric quantification of protein lysate arrays"],"prefix":"10.1093","volume":"23","author":[{"given":"Jianhua","family":"Hu","sequence":"first","affiliation":[{"name":"1 Department of Bioinformatics and Computational Biology, University of Texas M.D. Anderson Cancer Center, 2Department of Statistics, University of Illinois at Urbana-Champaign, 3Department of Gynecologic Medical Oncology and 4Department of Systems Biology, University of Texas M.D. Anderson Cancer Center, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuming","family":"He","sequence":"additional","affiliation":[{"name":"1 Department of Bioinformatics and Computational Biology, University of Texas M.D. Anderson Cancer Center, 2Department of Statistics, University of Illinois at Urbana-Champaign, 3Department of Gynecologic Medical Oncology and 4Department of Systems Biology, University of Texas M.D. Anderson Cancer Center, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith A.","family":"Baggerly","sequence":"additional","affiliation":[{"name":"1 Department of Bioinformatics and Computational Biology, University of Texas M.D. Anderson Cancer Center, 2Department of Statistics, University of Illinois at Urbana-Champaign, 3Department of Gynecologic Medical Oncology and 4Department of Systems Biology, University of Texas M.D. Anderson Cancer Center, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin R.","family":"Coombes","sequence":"additional","affiliation":[{"name":"1 Department of Bioinformatics and Computational Biology, University of Texas M.D. Anderson Cancer Center, 2Department of Statistics, University of Illinois at Urbana-Champaign, 3Department of Gynecologic Medical Oncology and 4Department of Systems Biology, University of Texas M.D. Anderson Cancer Center, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bryan T.J.","family":"Hennessy","sequence":"additional","affiliation":[{"name":"1 Department of Bioinformatics and Computational Biology, University of Texas M.D. Anderson Cancer Center, 2Department of Statistics, University of Illinois at Urbana-Champaign, 3Department of Gynecologic Medical Oncology and 4Department of Systems Biology, University of Texas M.D. Anderson Cancer Center, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gordon B.","family":"Mills","sequence":"additional","affiliation":[{"name":"1 Department of Bioinformatics and Computational Biology, University of Texas M.D. Anderson Cancer Center, 2Department of Statistics, University of Illinois at Urbana-Champaign, 3Department of Gynecologic Medical Oncology and 4Department of Systems Biology, University of Texas M.D. Anderson Cancer Center, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2007,6,28]]},"reference":[{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/ng1987","article-title":"A module of negative feedback regulators defines growth factor signaling","volume":"39","author":"Amit","year":"2006","journal-title":"Nat. Genet."},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1214\/aos\/1176349847","article-title":"Simulated power functions","volume":"14","author":"Beran","year":"1986","journal-title":"Ann. Stat."},{"key":"2023041105312749200_","first-page":"263","article-title":"Methods in functional proteomics: two-dimensional polyacrylamide gel electrophoresis with immobilized pH gradients, in-gel digestion and identification of proteins by mass spectrometry","volume":"250","author":"Bernard","year":"2004","journal-title":"Method Mol. Biol."},{"key":"2023041105312749200_","first-page":"177","article-title":"Protein arrays and their role in proteomics","volume":"83","author":"Cahill","year":"2003","journal-title":"Adv. Biochem. Eng. Biotechnol."},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1038\/labinvest.3780204","article-title":"Validation of tissue microarray technology in breast carcinoma","volume":"80","author":"Camp","year":"2000","journal-title":"Lab. Invest."},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1038\/nm1139","article-title":"Protein microarrays for multiplex analysis of signal transduction pathways","volume":"10","author":"Chan","year":"2004","journal-title":"Nat. Med."},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/S0076-6879(05)03017-X","article-title":"Assay of Rab25 function in ovarian and breast cancers","volume":"403","author":"Cheng","year":"2005","journal-title":"Method Enzymol."},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1126\/science.275.5300.661","article-title":"Regulation of neuronal survival by the serine-threonine protein kinase Akt","volume":"275","author":"Dudek","year":"1997","journal-title":"Science"},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1002\/pmic.200300592","article-title":"Protein microarrays: molecular profiling technologies for clinical specimens","volume":"3","author":"Espina","year":"2003","journal-title":"Proteomics"},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.jim.2004.04.013","article-title":"Protein microarray detection strategies: focus on direct detection technologies","volume":"290","author":"Espina","year":"2004","journal-title":"J. Immunol. Methods"},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s001800050019","article-title":"COBS: qualitatively constrained smoothing via linear program","volume":"14","author":"He","year":"1999","journal-title":"Comput. Stat."},{"key":"2023041105312749200_","first-page":"643","article-title":"Monotone B-spline smoothing","volume":"93","author":"He","year":"1998","journal-title":"J. Am. Stat. Assoc."},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1002\/pmic.200300461","article-title":"Mitochondrial proteome: altered cytochrome c oxidase subunit levels in prostate cancer","volume":"3","author":"Herrmann","year":"2003","journal-title":"Proteomics"},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"10436","DOI":"10.1074\/jbc.M212881200","article-title":"Proteome analysis reveals phosphorylation of ATP synthase beta-subunit in human skeletal muscle and proteins with potential roles in type 2 diabetes","volume":"278","author":"Hojlund","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1074\/mcp.M300130-MCP200","article-title":"Antibodies immobilized as arrays to profile protein post-translational modifications in mammalian cells","volume":"3","author":"Ivanov","year":"2004","journal-title":"Mol. Cell Proteomics"},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"2964","DOI":"10.1002\/pmic.200500555","article-title":"Pathway alterations during glioma progression revealed by reverse phase protein lysate arrays","volume":"6","author":"Jiang","year":"2006","journal-title":"Proteomics"},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.metabol.2003.12.002","article-title":"The relationship between glycemic control and plasma vascular endothelial growth factor and endothelin-1 concentration in diabetic patients","volume":"53","author":"Kakizawa","year":"2004","journal-title":"Metabolism"},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/0304-4076(96)84507-6","article-title":"An interior point algorithm for nonlinear quantile regression","volume":"71","author":"Koenker","year":"1994","journal-title":"J. Econom."},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1038\/nm0798-844","article-title":"Tissue microarray for high-throughput molecular profiling of tumor specimens","volume":"4","author":"Kononen","year":"1998","journal-title":"Nat. Med."},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1515\/CCLM.2003.023","article-title":"Detection of multiple cytokines by protein arrays from cell lysate and tissue lysate","volume":"41","author":"Lin","year":"2003","journal-title":"Clin. Chem. Lab. Med."},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1016\/S0002-9440(10)64434-3","article-title":"Software tools for high-throughput analysis and archiving of immunohi-stochemistry staining data obtained with tissue microarrays","volume":"161","author":"Liu","year":"2002","journal-title":"Am. J. Pathol."},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1038\/ng1037","article-title":"Protein microarrays and proteomics","volume":"32","author":"MacBeath","year":"2002","journal-title":"Nat. Genet."},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1126\/science.289.5485.1760","article-title":"Printing proteins as microarrays for high-throughput function determination","volume":"289","author":"MacBeath","year":"2000","journal-title":"Science"},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1093\/bioinformatics\/bti258","article-title":"Robust estimation of protein expression ratios with lysate microarray technology","volume":"21","author":"Mircean","year":"2005","journal-title":"Bioinformatics"},{"key":"2023041105312749200_","article-title":"Individualized molecular medicine: linking functional proteomics to select therapeutics targeting the PI3K pathway for specific patients.","author":"Murph","year":"2006","journal-title":"Ovarian Cancer: State of the Art and Future Directions in Translational Research"},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"14229","DOI":"10.1073\/pnas.2331323100","article-title":"Proteomic profiling of the NCI-60 cancer cell lines using new high-density reverse-phase lysate microarrays","volume":"100","author":"Nishizuka","year":"2003","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023041105312749200_","first-page":"5243","article-title":"Diagnostic markers that distinguish colon and ovarian adenocarcinomas: identification by genomic proteomic and tissue array profiling","volume":"63","author":"Nishizuka","year":"2003","journal-title":"Cancer Res."},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/S1046-2023(02)00303-1","article-title":"Mass spectrometric-based approaches in quantitative proteomics","volume":"29","author":"Ong","year":"2003","journal-title":"Methods"},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1136\/mp.56.4.198","article-title":"Demystified \u2026 tissue microarray technology","volume":"56","author":"Packeisen","year":"2003","journal-title":"Mol. Pathol."},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1038\/sj.onc.1204265","article-title":"Reverse phase protein microarrays which capture disease progression show activation of pro-survival pathways at the cancer invasion front","volume":"20","author":"Paweletz","year":"2001","journal-title":"Oncogene"},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1477-5956-3-9","article-title":"Application of protein lysate microarrays to molecular marker verification and quantification","volume":"3","author":"Ramaswamy","year":"2005","journal-title":"Proteome Sci."},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1083\/jcb.200603161","article-title":"New consensus nomenclature for mammalian keratins","volume":"174","author":"Schweizer","year":"2006","journal-title":"J. Cell. Biol."},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1074\/mcp.T500003-MCP200","article-title":"Use of reverse phase protein microarrays and reference standard development for molecular network analysis of metastatic ovarian carcinoma","volume":"4","author":"Sheehan","year":"2005","journal-title":"Mol. Cell. Proteomics"},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"2394","DOI":"10.1109\/TSP.2006.873719","article-title":"Nonlinear modeling of protein expressions in protein arrays","volume":"54","author":"Tabus","year":"2006","journal-title":"IEEE Trans. Signal Processing"},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"2512","DOI":"10.1158\/1535-7163.MCT-06-0334","article-title":"Reverse phase protein array (RPPA): validation of a novel proteomic technology and utility for analysis of primary leukemia specimens and hematopoetic stem cells (HSC)","volume":"5","author":"Tibes","year":"2006","journal-title":"Mol. Cancer. Ther."},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1089\/154065803322302772","article-title":"A \u2018mix and read\u2019 assay for insulin using fluorometric microvolume assay technology","volume":"1","author":"Toney","year":"2003","journal-title":"Assay Drug Dev. Technol."},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"2249","DOI":"10.1016\/S0002-9440(10)63075-1","article-title":"Tissue microarrays for rapid linking of molecular changes to clinical endpoints","volume":"159","author":"Torhorst","year":"2001","journal-title":"Am. J. Pathol."},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1002\/pmic.200300591","article-title":"Signal pathway profiling of ovarian cancer from human tissue specimens using reverse-phase protein microarrays","volume":"3","author":"Wulfkuhle","year":"2003","journal-title":"Proteomics"},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1002\/pmic.200300443","article-title":"Protein microarrays using liquid phase fractionation of cell lysates","volume":"3","author":"Yan","year":"2003","journal-title":"Proteomics"},{"key":"2023041105312749200_","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/labinvest.3700051","article-title":"Similarities of prosurvival signals in Bcl-2-positive and Bcl-2-negative follicular lymphomas identified by reverse phase protein microarray","volume":"84","author":"Zha","year":"2004","journal-title":"Lab. Invest."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/23\/15\/1986\/49814671\/bioinformatics_23_15_1986.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/23\/15\/1986\/49814671\/bioinformatics_23_15_1986.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T18:53:29Z","timestamp":1683917609000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/23\/15\/1986\/205819"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,6,28]]},"references-count":40,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2007,8,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btm283","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2007,8]]},"published":{"date-parts":[[2007,6,28]]}}}