Abstract

BackgroundThere is great current interest in developing microarray platforms for measuring mRNA abundance at both gene level and exon level. The Affymetrix Exon Array is a new high-density gene expression microarray platform, with over six million probes targeting all annotated and predicted exons in a genome. An important question for the analysis of exon array data is how to compute overall gene expression indexes. Because of the complexity of the design of exon array probes, this problem is different in nature from summarizing gene-level expression from traditional 3′ expression arrays.Methodology/Principal FindingsIn this manuscript, we use exon array data from 11 human tissues to study methods for computing gene-level expression. We showed that for most genes there is a subset of exon array probes having highly correlated intensities across multiple samples. We suggest that these probes could be used as reliable indicators of overall gene expression levels. We developed a probe selection algorithm to select such a subset of highly correlated probes for each gene, and computed gene expression indexes using the selected probes.Conclusions/SignificanceOur results demonstrate that probe selection improves gene expression estimates from exon arrays. The selected probes can be used in future analyses of other exon array datasets to compute gene expression indexes.

Highlights

  • Microarrays have become one of the most popular technologies for profiling gene expression since its invention more than a decade ago [1,2,3]

  • We present our probe-level analysis of the exon array data, and describe a probe selection strategy for computing gene expression indexes from Exon Arrays

  • We normalized the data by sketch normalization using the Affymetrix Exon Array Computational Tool (ExACT)

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Summary

Introduction

Microarrays have become one of the most popular technologies for profiling gene expression since its invention more than a decade ago [1,2,3]. A variety of gene expression microarray platforms are used today, including spotted cDNA arrays, Affymetrix GeneChip arrays, Agilent ink-jet arrays and Illumina long-oligonucleotide beadbased arrays [4,5]. These microarray platforms differ in their probe design, hybridization protocol, labeling and production methods [4,5]. We showed that for most genes there is a subset of exon array probes having highly correlated intensities across multiple samples We suggest that these probes could be used as reliable indicators of overall gene expression levels. The selected probes can be used in future analyses of other exon array datasets to compute gene expression indexes

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