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Finding regulatory DNA motifs using alignment-free evolutionary conservation information.

Publication ,  Journal Article
Gordân, R; Narlikar, L; Hartemink, AJ
Published in: Nucleic Acids Res
April 2010

As an increasing number of eukaryotic genomes are being sequenced, comparative studies aimed at detecting regulatory elements in intergenic sequences are becoming more prevalent. Most comparative methods for transcription factor (TF) binding site discovery make use of global or local alignments of orthologous regulatory regions to assess whether a particular DNA site is conserved across related organisms, and thus more likely to be functional. Since binding sites are usually short, sometimes degenerate, and often independent of orientation, alignment algorithms may not align them correctly. Here, we present a novel, alignment-free approach for using conservation information for TF binding site discovery. We relax the definition of conserved sites: we consider a DNA site within a regulatory region to be conserved in an orthologous sequence if it occurs anywhere in that sequence, irrespective of orientation. We use this definition to derive informative priors over DNA sequence positions, and incorporate these priors into a Gibbs sampling algorithm for motif discovery. Our approach is simple and fast. It requires neither sequence alignments nor the phylogenetic relationships between the orthologous sequences, yet it is more effective on real biological data than methods that do.

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Published In

Nucleic Acids Res

DOI

EISSN

1362-4962

Publication Date

April 2010

Volume

38

Issue

6

Start / End Page

e90

Location

England

Related Subject Headings

  • Transcription Factors
  • Sequence Analysis, DNA
  • Sequence Alignment
  • Promoter Regions, Genetic
  • Molecular Sequence Data
  • Developmental Biology
  • Conserved Sequence
  • Binding Sites
  • Base Sequence
  • 41 Environmental sciences
 

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Gordân, R., Narlikar, L., & Hartemink, A. J. (2010). Finding regulatory DNA motifs using alignment-free evolutionary conservation information. Nucleic Acids Res, 38(6), e90. https://doi.org/10.1093/nar/gkp1166
Gordân, Raluca, Leelavati Narlikar, and Alexander J. Hartemink. “Finding regulatory DNA motifs using alignment-free evolutionary conservation information.Nucleic Acids Res 38, no. 6 (April 2010): e90. https://doi.org/10.1093/nar/gkp1166.
Gordân R, Narlikar L, Hartemink AJ. Finding regulatory DNA motifs using alignment-free evolutionary conservation information. Nucleic Acids Res. 2010 Apr;38(6):e90.
Gordân, Raluca, et al. “Finding regulatory DNA motifs using alignment-free evolutionary conservation information.Nucleic Acids Res, vol. 38, no. 6, Apr. 2010, p. e90. Pubmed, doi:10.1093/nar/gkp1166.
Gordân R, Narlikar L, Hartemink AJ. Finding regulatory DNA motifs using alignment-free evolutionary conservation information. Nucleic Acids Res. 2010 Apr;38(6):e90.
Journal cover image

Published In

Nucleic Acids Res

DOI

EISSN

1362-4962

Publication Date

April 2010

Volume

38

Issue

6

Start / End Page

e90

Location

England

Related Subject Headings

  • Transcription Factors
  • Sequence Analysis, DNA
  • Sequence Alignment
  • Promoter Regions, Genetic
  • Molecular Sequence Data
  • Developmental Biology
  • Conserved Sequence
  • Binding Sites
  • Base Sequence
  • 41 Environmental sciences