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Bioinformatics 2005 21(Suppl 1):i338-i343; doi:10.1093/bioinformatics/bti1047
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© The Author 2005. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions{at}oupjournals.org

Predicting the in vivo signature of human gene regulatory sequences

William Stafford Noble 1,*, Scott Kuehn 2, Robert Thurman 2, Man Yu 2 and John Stamatoyannopoulos 3

1Department of Genome Sciences and Department of Computer Science and Engineering, University of Washington Seattle, WA, USA
2Division of Medical Genetics, University of Washington Seattle, WA, USA
3Department of Molecular Biology Regulome, 2211 Elliott Avenue, Suite 600, Seattle, WA 98121, USA

*To whom correspondence should be addressed.

Motivation: In the living cell nucleus, genomic DNA is packaged into chromatin. DNA sequences that regulate transcription and other chromosomal processes are associated with local disruptions, or ‘openings’, in chromatin structure caused by the cooperative action of regulatory proteins. Such perturbations are extremely specific for cis-regulatory elements and occur over short stretches of DNA (typically ~250 bp). They can be detected experimentally as DNaseI hypersensitive sites (HSs) in vivo, though the process is extremely laborious and costly. The ability to discriminate DNaseI HSs computationally would have a major impact on the annotation and utilization of the human genome.

Results: We found that a supervised pattern recognition algorithm, trained using a set of 280 DNaseI HS and 737 non-HS control sequences from erythroid cells, was capable of de novo prediction of HSs across the human genome with surprisingly high accuracy determined by prospective in vivo validation. Systematic application of this computational approach will greatly facilitate the discovery and analysis of functional non-coding elements in the human and other complex genomes.

Availability: Supplementary data is available at noble.gs.washington.edu/proj/hs

Contact: noble{at}gs.washington.edu; jstam{at}regulome.com

Received on January 15, 2005; accepted on March 27, 2005

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