A Random Coefficients Model for Regional Coexpression Associated with DNA Copy Number Aberrations

• Activity Number: 603
• Type: Invited
• Date/Time: Thursday, August 5, 2010 : 8:30 AM to 10:20 AM
• Sponsor: WNAR
• Author(s): Wessel Van Wieringen*+
• Companies: VU University Medical Center
• Keywords: Bootstrap ; Constrained estimation ; Data integration ; Microarray

Abstract

We integrate coupled DNA copy number and gene expression data in order to study regional co-expression, i.e. the phenomenon of neighborhoods of contiguous genes showing similar expression patterns. Such neighborhoods appear throughout the cancer genome and often coincide with copy number aberrations (CNA). We use a random coefficients model to link copy number data of a genomic region to its genes' expression data. The model facilitates a global analysis of regional co-expression at the level of the region (rather than its genes) to assess whether a) there is a shared CNA effect on expression levels of genes within the region, and b) the CNA effect is identical for all genes. To estimate the parameters from high-throughput data, we optimize estimation wrt computational speed and memory use, while incorporating prior knowledge on the parameters. Two examples illustrate the methodology.