The use of semiparametric mixed models to analyze PamChip(R) peptide array data: an application to an oncology experiment

Bioinformatics. 2011 Oct 15;27(20):2859-65. doi: 10.1093/bioinformatics/btr475. Epub 2011 Aug 16.

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 PamChip(®) microarray technology. We propose a flexible semiparametric mixed model for analyzing PamChip(®) 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, 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.

Contact: pushpike@med.kuleuven.be

Supplementary information: Supplementary data are available at Bioinformatics online.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Confidence Intervals
  • Humans
  • Microarray Analysis / methods*
  • Models, Statistical*
  • Peptides / metabolism*
  • Phosphorylation
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinases / metabolism

Substances

  • Peptides
  • Protein Kinase Inhibitors
  • Protein Kinases