4 research outputs found
Modeling association between DNA copy number and gene expression with constrained piecewise linear regression splines
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.Comment: 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
PLRS Piecewise Linear Regression Splines for the association between DNA copy number and
The PLRS package implements the methodology described by [2] for the joint analysis of DNA copy number and mRNA expression. The framework employs piecewise linear regression splines (PLRS), a broad class of interpretable models, to model cis-relationships between the two molecular levels. In the present vignette, we provide guidance for
Matching of array CGH and gene expression microarray features for the purpose of integrative genomic analyses
<p>Abstract</p> <p>Background</p> <p>An increasing number of genomic studies interrogating more than one molecular level is published. Bioinformatics follows biological practice, and recent years have seen a surge in methodology for the integrative analysis of genomic data. Often such analyses require knowledge of which elements of one platform link to those of another. Although important, many integrative analyses do not or insufficiently detail the matching of the platforms.</p> <p>Results</p> <p>We describe, illustrate and discuss six matching procedures. They are implemented in the R-package sigaR (available from Bioconductor). The principles underlying the presented matching procedures are generic, and can be combined to form new matching approaches or be applied to the matching of other platforms. Illustration of the matching procedures on a variety of data sets reveals how the procedures differ in the use of the available data, and may even lead to different results for individual genes.</p> <p>Conclusions</p> <p>Matching of data from multiple genomics platforms is an important preprocessing step for many integrative bioinformatic analysis, for which we present six generic procedures, both old and new. They have been implemented in the R-package sigaR, available from Bioconductor.</p