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Title: | The use of semiparametric mixed models to analyze PamChip® peptide array data: an application to an oncology experiment | Authors: | THILAKARATHNE, Pushpike CLEMENT, Lieven LIN, Dan SHKEDY, Ziv KASIM, Adetayo TALLOEN, Willem Versele, Matthias VERBEKE, Geert |
Issue Date: | 2011 | Publisher: | OXFORD UNIV PRESS | Source: | BIOINFORMATICS, 27(20), p. 2859-2865 | Abstract: | 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 PamChipr microarray technology. we propose a flexible semi-parametric mixed model for analyzing PamChipr data. This approach enables the estimation of the phosphorylation rate (Velocity) as a function of time together with pointwise confidence intervals. Results: Using a publicly available dataset (Versele et al., 2009), 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. | Keywords: | Reprint Address: Thilakarathne, PJ (reprint author), Katholieke Univ Leuven, Interuniv Inst Biostat & Stat Bioinformat, B-3000 Louvain, Belgium Addresses: 1. Katholieke Univ Leuven, Interuniv Inst Biostat & Stat Bioinformat, B-3000 Louvain, Belgium 2. Univ Hasselt, Interuniv Inst Biostat & Stat Bioinformat, B-3590 Diepenbeek, Belgium 3. Durham Univ Queens Campus, Wolfson Res Inst, Thornaby, Stockton On Tee, England 4. Janssen Pharmaceut NV, Beerse, Belgium E-mail Address: pushpike@med.kuleuven.be | Document URI: | http://hdl.handle.net/1942/12952 | Link to publication/dataset: | http://bioinformatics.oxfordjournals.org/content/27/20/2859.abstract | ISSN: | 1367-4803 | e-ISSN: | 1367-4811 | DOI: | 10.1093/bioinformatics/btr475 | ISI #: | 000295680600012 | Rights: | The Author 2011. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2012 |
Appears in Collections: | Research publications |
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