Modeling association between DNA copy number and gene expression with constrained piecewise linear regression splines
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.
Keywords
Cite
@article{arxiv.1312.1795,
title = {Modeling association between DNA copy number and gene expression with constrained piecewise linear regression splines},
author = {Gwenaël G. R. Leday and Aad W. van der Vaart and Wessel N. van Wieringen and Mark A. van de Wiel},
journal= {arXiv preprint arXiv:1312.1795},
year = {2013}
}
Comments
Published in at http://dx.doi.org/10.1214/12-AOAS605 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org)