Methodology article

Background correction using dinucleotide affinities improves the performance of GCRMA

Raad Z Gharaibeh , Anthony A Fodor and Cynthia J Gibas

Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, NC, 28223, USA

author email corresponding author email

BMC Bioinformatics 2008, 9:452doi:10.1186/1471-2105-9-452

Published:	23 October 2008

Abstract

Background

High-density short oligonucleotide microarrays are a primary research tool for assessing global gene expression. Background noise on microarrays comprises a significant portion of the measured raw data, which can have serious implications for the interpretation of the generated data if not estimated correctly.

Results

We introduce an approach to calculate probe affinity based on sequence composition, incorporating nearest-neighbor (NN) information. Our model uses position-specific dinucleotide information, instead of the original single nucleotide approach, and adds up to 10% to the total variance explained (R²) when compared to the previously published model. We demonstrate that correcting for background noise using this approach enhances the performance of the GCRMA preprocessing algorithm when applied to control datasets, especially for detecting low intensity targets.

Conclusion

Modifying the previously published position-dependent affinity model to incorporate dinucleotide information significantly improves the performance of the model. The dinucleotide affinity model enhances the detection of differentially expressed genes when implemented as a background correction procedure in GeneChip preprocessing algorithms. This is conceptually consistent with physical models of binding affinity, which depend on the nearest-neighbor stacking interactions in addition to base-pairing.