title: Allele-specific expression analysis methods for high-density SNP microarray data.
abstract: BACKGROUND
  In the past decade, a number of technologies to quantify allele-specific expression (ASE) in a genome-wide manner have become available to researchers. We investigate the application of single-nucleotide polymorphism (SNP) microarrays to this task, exploring data obtained from both cell lines and primary tissue for which both RNA and DNA profiles are available.
  
  
  RESULTS
  We analyze data from two experiments that make use of high-density Illumina Infinium II genotyping arrays to measure ASE. We first preprocess each data set, which involves removal of outlier samples, careful normalization and a two-step filtering procedure to remove SNPs that show no evidence of expression in the samples being analyzed and calls that are clear genotyping errors. We then compare three different tests for detecting ASE, one of which has been previously published and two novel approaches. These tests vary at the level at which they operate (per SNP per individual or per SNP) and in the input data they require. Using SNPs from imprinted genes as true positives for ASE, we observe varying sensitivity for the different testing procedures that improves with increasing sample size. Methods that rely on RNA signal alone were found to perform best across a range of metrics. The top ranked SNPs recovered by all methods appear to be reasonable candidates for ASE.
  
  
  METHODS
  Analysis was carried out in R (http://www.R-project.org/) using existing functions.
authors.affiliation: Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
authors.forename: Ruijie
authors.initials: R
authors.lastname: Liu
authors.forename: Ana-Teresa
authors.initials: AT
authors.lastname: Maia
authors.forename: Roslin
authors.initials: R
authors.lastname: Russell
authors.forename: Carlos
authors.initials: C
authors.lastname: Caldas
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Ponder
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Ritchie
mesh_terms: D000483:Alleles; D055106:Genome-Wide Association Study; D018392:Genomic Imprinting; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D012984:Software