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Bioinformatics Advance Access published online on June 20, 2006
Bioinformatics, doi:10.1093/bioinformatics/btl289
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© 2006 The Author(s)
Received April 3, 2006
Accepted May 24, 2006

Article

Transcript mapping with high-density oligonucleotide tiling arrays

Wolfgang Huber 1 *, Joern Toedling 1, and Lars M. Steinmetz 2

1 European Molecular Biology Laboratory, European Bioinformatics Institute, Cambridge CB10 1SD, UK
2 European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany

* To whom correspondence should be addressed.
Wolfgang Huber, E-mail: huber{at}ebi.ac.uk


  Abstract

Motivation: High-density DNA tiling microarrays are a powerful tool for the characterization of complete transcriptomes. The two major analytical challenges are the segmentation of the hybridization signal along genomic coordinates to accurately determine transcript boundaries and the adjustment of the sequence-dependent response of the oligonucleotide probes to achieve quantitative comparability of the signal between different probes.

Results: We describe a dynamic programming algorithm for finding a globally optimal fit of a piecewise constant expression profile along genomic coordinates. We developed a probe-specific background correction and scaling method that employs empirical probe response parameters determined from reference hybridizations with no need for paired mismatch (MM) probes. This combined analysis approach allows the accurate determination of dynamical changes in transcription architectures from hybridization data and will help to study the biological significance of complex transcriptional phenomena in eukaryotic genomes.

Availability: R package tilingArray at www.bioconductor.org.

Associate Editor: Joaquin Dopazo
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