{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T13:21:39Z","timestamp":1765545699660,"version":"3.38.0"},"reference-count":16,"publisher":"Oxford University Press (OUP)","issue":"20","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: Phosphorylation by protein kinases is a central theme in biological systems. Aberrant protein kinase activity has been implicated in a variety of human diseases (e.g. cancer). Therefore, modulation of kinase activity represents an attractive therapeutic approach for the treatment of human illnesses. Thus, identification of signature peptides is crucial for protein kinase targeting and can be achieved by using PamChip\u00ae microarray technology. We propose a flexible semiparametric mixed model for analyzing PamChip\u00ae data. This approach enables the estimation of the phosphorylation rate (Velocity) as a function of time together with pointwise confidence intervals.<\/jats:p><jats:p>Results: Using a publicly available dataset, we show that our model is capable of adequately fitting the kinase activity profiles and provides velocity estimates over time. Moreover, it allows to test for differences in the velocity of kinase inhibition between responding and non-responding cell lines. This can be done at individual time point as well as for the entire velocity profile.<\/jats:p><jats:p>Contact: \u00a0pushpike@med.kuleuven.be<\/jats:p><jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btr475","type":"journal-article","created":{"date-parts":[[2011,8,17]],"date-time":"2011-08-17T01:16:54Z","timestamp":1313543814000},"page":"2859-2865","source":"Crossref","is-referenced-by-count":8,"title":["The use of semiparametric mixed models to analyze PamChip\u00ae peptide array data: an application to an oncology experiment"],"prefix":"10.1093","volume":"27","author":[{"given":"Pushpike J.","family":"Thilakarathne","sequence":"first","affiliation":[{"name":"1 Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Katholieke Universiteit Leuven, B3000 Leuven, 2Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Universiteit Hasselt, Agoralaan 1, B3590 Diepenbeek, Belgium, 3Wolfson Research Institute, Durham University Queen's Campus, University Boulevard, Thornaby, Stockton-on-Tees, UK and 4Janssen Pharmaceutica N.V., Beerse, Belgium"}]},{"given":"Lieven","family":"Clement","sequence":"additional","affiliation":[{"name":"1 Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Katholieke Universiteit Leuven, B3000 Leuven, 2Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Universiteit Hasselt, Agoralaan 1, B3590 Diepenbeek, Belgium, 3Wolfson Research Institute, Durham University Queen's Campus, University Boulevard, Thornaby, Stockton-on-Tees, UK and 4Janssen Pharmaceutica N.V., Beerse, Belgium"},{"name":"1 Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Katholieke Universiteit Leuven, B3000 Leuven, 2Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Universiteit Hasselt, Agoralaan 1, B3590 Diepenbeek, Belgium, 3Wolfson Research Institute, Durham University Queen's Campus, University Boulevard, Thornaby, Stockton-on-Tees, UK and 4Janssen Pharmaceutica N.V., Beerse, Belgium"}]},{"given":"Dan","family":"Lin","sequence":"additional","affiliation":[{"name":"1 Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Katholieke Universiteit Leuven, B3000 Leuven, 2Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Universiteit Hasselt, Agoralaan 1, B3590 Diepenbeek, Belgium, 3Wolfson Research Institute, Durham University Queen's Campus, University Boulevard, Thornaby, Stockton-on-Tees, UK and 4Janssen Pharmaceutica N.V., Beerse, Belgium"},{"name":"1 Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Katholieke Universiteit Leuven, B3000 Leuven, 2Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Universiteit Hasselt, Agoralaan 1, B3590 Diepenbeek, Belgium, 3Wolfson Research Institute, Durham University Queen's Campus, University Boulevard, Thornaby, Stockton-on-Tees, UK and 4Janssen Pharmaceutica N.V., Beerse, Belgium"}]},{"given":"Ziv","family":"Shkedy","sequence":"additional","affiliation":[{"name":"1 Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Katholieke Universiteit Leuven, B3000 Leuven, 2Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Universiteit Hasselt, Agoralaan 1, B3590 Diepenbeek, Belgium, 3Wolfson Research Institute, Durham University Queen's Campus, University Boulevard, Thornaby, Stockton-on-Tees, UK and 4Janssen Pharmaceutica N.V., Beerse, Belgium"}]},{"given":"Adetayo","family":"Kasim","sequence":"additional","affiliation":[{"name":"1 Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Katholieke Universiteit Leuven, B3000 Leuven, 2Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Universiteit Hasselt, Agoralaan 1, B3590 Diepenbeek, Belgium, 3Wolfson Research Institute, Durham University Queen's Campus, University Boulevard, Thornaby, Stockton-on-Tees, UK and 4Janssen Pharmaceutica N.V., Beerse, Belgium"}]},{"given":"Willem","family":"Talloen","sequence":"additional","affiliation":[{"name":"1 Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Katholieke Universiteit Leuven, B3000 Leuven, 2Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Universiteit Hasselt, Agoralaan 1, B3590 Diepenbeek, Belgium, 3Wolfson Research Institute, Durham University Queen's Campus, University Boulevard, Thornaby, Stockton-on-Tees, UK and 4Janssen Pharmaceutica N.V., Beerse, Belgium"}]},{"given":"Matthias","family":"Versele","sequence":"additional","affiliation":[{"name":"1 Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Katholieke Universiteit Leuven, B3000 Leuven, 2Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Universiteit Hasselt, Agoralaan 1, B3590 Diepenbeek, Belgium, 3Wolfson Research Institute, Durham University Queen's Campus, University Boulevard, Thornaby, Stockton-on-Tees, UK and 4Janssen Pharmaceutica N.V., Beerse, Belgium"}]},{"given":"Geert","family":"Verbeke","sequence":"additional","affiliation":[{"name":"1 Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Katholieke Universiteit Leuven, B3000 Leuven, 2Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Universiteit Hasselt, Agoralaan 1, B3590 Diepenbeek, Belgium, 3Wolfson Research Institute, Durham University Queen's Campus, University Boulevard, Thornaby, Stockton-on-Tees, UK and 4Janssen Pharmaceutica N.V., Beerse, Belgium"}]}],"member":"286","published-online":{"date-parts":[[2011,8,16]]},"reference":[{"key":"2023012512011710200_B1","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B"},{"key":"2023012512011710200_B2","doi-asserted-by":"crossref","DOI":"10.1093\/oso\/9780198523963.001.0001","volume-title":"Applied Smoothing Techniques for Data Analysis.","author":"Bowman","year":"1997"},{"key":"2023012512011710200_B3","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1002\/sim.1991","article-title":"Simple fitting of subject-specific curves for longitudinal data","volume":"24","author":"Durb\u00e1n","year":"2004","journal-title":"Stat. Med."},{"key":"2023012512011710200_B4","doi-asserted-by":"crossref","DOI":"10.1201\/9781420011579","volume-title":"Longitudinal Data Analysis.","author":"Fitzmaurice","year":"2008"},{"key":"2023012512011710200_B5","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.ab.2009.01.022","article-title":"Peptide microarrays for detailed, high-throughput substrate identification, kinetic characterization, and inhibition studies on protein kinase A","volume":"387","author":"Hilhorst","year":"2009","journal-title":"Anal. Biochem."},{"key":"2023012512011710200_B6","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.jaad.2005.02.011","article-title":"The promise of molecular targeted therapies: Protein kinase inhibitors in the treatment of cutaneous malignancies","volume":"53","author":"Kondapalli","year":"2005","journal-title":"J. Am. Acad. Dermatol."},{"key":"2023012512011710200_B7","doi-asserted-by":"crossref","first-page":"6009","DOI":"10.1002\/sim.3363","article-title":"Analysis of cross-over designs with serial correlation within periods using semi-parametric mixed models","volume":"27","author":"Maringwa","year":"2008","journal-title":"Stat. Med."},{"key":"2023012512011710200_B8","doi-asserted-by":"crossref","first-page":"5187","DOI":"10.1128\/JCM.43.10.5187-5194.2005","article-title":"Use of a three-dimensional microarray system for detection of levofloxacin resistance and the mec A gene in Staphylococcus aureus","volume":"43","author":"Nagaoka","year":"2005","journal-title":"J. Clin. Microbiol."},{"key":"2023012512011710200_B9","article-title":"Models for discrete longitudinal data","volume-title":"Springer Series in Statistics.","author":"Molenberghs","year":"2005"},{"key":"2023012512011710200_B10","first-page":"178","article-title":"JNJ-26483327 is a novel multi-targeted tyrosine kinase inhibitor with cellular activity against EGFR, Her2, Src and VEGFR3","volume":"4","author":"Perera","year":"2006","journal-title":"EJC"},{"key":"2023012512011710200_B11","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4419-0318-1","article-title":"Mixed-Effects Models in S and S-PLUS","volume-title":"Springer Series in Statistics and Computing.","author":"Pinheiro","year":"2000"},{"key":"2023012512011710200_B12","doi-asserted-by":"crossref","DOI":"10.1007\/b98888","volume-title":"Functional Data Analysis","author":"Ramsay","year":"2005","edition":"2"},{"key":"2023012512011710200_B13","doi-asserted-by":"crossref","DOI":"10.1017\/CBO9780511755453","volume-title":"Semiparametric Regression.","author":"Ruppert","year":"2003"},{"key":"2023012512011710200_B14","article-title":"Linear Mixed Models for Longitudinal Data","volume-title":"Springer Series in Statistics.","author":"Verbeke","year":"2000"},{"key":"2023012512011710200_B15","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1158\/1535-7163.MCT-08-1029","article-title":"Response prediction to a multitargeted kinase inhibitor in cancer cell lines and xenograft tumors using high-content tyrosine peptide arrays with a kinetic readout","volume":"8","author":"Versele","year":"2009","journal-title":"Mol. Cancer Therap."},{"key":"2023012512011710200_B16","doi-asserted-by":"crossref","DOI":"10.1201\/9781420010404","volume-title":"Generalized Additive Models: An Introduction with R.","author":"Wood","year":"2006"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/27\/20\/2859\/48870342\/bioinformatics_27_20_2859.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/27\/20\/2859\/48870342\/bioinformatics_27_20_2859.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,8]],"date-time":"2025-03-08T20:51:16Z","timestamp":1741467076000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/27\/20\/2859\/201703"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,8,16]]},"references-count":16,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2011,10,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btr475","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"type":"electronic","value":"1367-4811"},{"type":"print","value":"1367-4803"}],"subject":[],"published-other":{"date-parts":[[2011,10,15]]},"published":{"date-parts":[[2011,8,16]]}}}