Transcript mapping with high-density oligonucleotide tiling arrays

Bioinformatics. 2006 Aug 15;22(16):1963-70. doi: 10.1093/bioinformatics/btl289. Epub 2006 Jun 20.

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 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 http://www.bioconductor.org.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Computational Biology / methods*
  • DNA / chemistry
  • Gene Expression Profiling / methods*
  • Genome
  • Models, Statistical
  • Nucleic Acid Hybridization
  • Oligonucleotide Array Sequence Analysis / methods*
  • Oligonucleotide Probes / genetics
  • Oligonucleotides / chemistry*
  • RNA, Messenger / metabolism*
  • Saccharomyces cerevisiae / metabolism
  • Transcription, Genetic

Substances

  • Oligonucleotide Probes
  • Oligonucleotides
  • RNA, Messenger
  • DNA