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June 2013 Modeling association between DNA copy number and gene expression with constrained piecewise linear regression splines
Gwenaël G. R. Leday, Aad W. van der Vaart, Wessel N. van Wieringen, Mark A. van de Wiel
Ann. Appl. Stat. 7(2): 823-845 (June 2013). DOI: 10.1214/12-AOAS605

Abstract

DNA copy number and mRNA expression are widely used data types in cancer studies, which combined provide more insight than separately. Whereas in existing literature the form of the relationship between these two types of markers is fixed a priori, in this paper we model their association. We employ piecewise linear regression splines (PLRS), which combine good interpretation with sufficient flexibility to identify any plausible type of relationship. The specification of the model leads to estimation and model selection in a constrained, nonstandard setting. We provide methodology for testing the effect of DNA on mRNA and choosing the appropriate model. Furthermore, we present a novel approach to obtain reliable confidence bands for constrained PLRS, which incorporates model uncertainty. The procedures are applied to colorectal and breast cancer data. Common assumptions are found to be potentially misleading for biologically relevant genes. More flexible models may bring more insight in the interaction between the two markers.

Citation

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Gwenaël G. R. Leday. Aad W. van der Vaart. Wessel N. van Wieringen. Mark A. van de Wiel. "Modeling association between DNA copy number and gene expression with constrained piecewise linear regression splines." Ann. Appl. Stat. 7 (2) 823 - 845, June 2013. https://doi.org/10.1214/12-AOAS605

Information

Published: June 2013
First available in Project Euclid: 27 June 2013

zbMATH: 1288.62161
MathSciNet: MR3112919
Digital Object Identifier: 10.1214/12-AOAS605

Keywords: confidence bands , constrained inference , DNA copy number , Model selection , mRNA expression , regression splines

Rights: Copyright © 2013 Institute of Mathematical Statistics

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Vol.7 • No. 2 • June 2013
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