Transcript mapping with high-density oligonucleotide tiling arrays.
BACKGROUND
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 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.


BACKGROUND
R package tilingArray at http://www.bioconductor.org.
Huber
Wolfgang
W
European Molecular Biology Laboratory, European Bioinformatics Institute, Cambridge CB10 1SD, UK. huber@ebi.ac.uk
Toedling
Joern
J
Steinmetz
Lars M
LM
D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D004247:DNA / Q000737:chemistry; D020869:Gene Expression Profiling / Q000379:methods*; D016678:Genome; D015233:Models, Statistical; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D015345:Oligonucleotide Probes / Q000235:genetics; D009841:Oligonucleotides / Q000737:chemistry*; D012333:RNA, Messenger / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D014158:Transcription, Genetic
D015345:Oligonucleotide Probes; D009841:Oligonucleotides; D012333:RNA, Messenger; D004247:DNA