title: BLSSpeller: exhaustive comparative discovery of conserved cis-regulatory elements.
abstract: BACKGROUND
  The accurate discovery and annotation of regulatory elements remains a challenging problem. The growing number of sequenced genomes creates new opportunities for comparative approaches to motif discovery. Putative binding sites are then considered to be functional if they are conserved in orthologous promoter sequences of multiple related species. Existing methods for comparative motif discovery usually rely on pregenerated multiple sequence alignments, which are difficult to obtain for more diverged species such as plants. As a consequence, misaligned regulatory elements often remain undetected.
  
  
  RESULTS
  We present a novel algorithm that supports both alignment-free and alignment-based motif discovery in the promoter sequences of related species. Putative motifs are exhaustively enumerated as words over the IUPAC alphabet and screened for conservation using the branch length score. Additionally, a confidence score is established in a genome-wide fashion. In order to take advantage of a cloud computing infrastructure, the MapReduce programming model is adopted. The method is applied to four monocotyledon plant species and it is shown that high-scoring motifs are significantly enriched for open chromatin regions in Oryza sativa and for transcription factor binding sites inferred through protein-binding microarrays in O.sativa and Zea mays. Furthermore, the method is shown to recover experimentally profiled ga2ox1-like KN1 binding sites in Z.mays.
  
  
  METHODS
  BLSSpeller was written in Java. Source code and manual are available at http://bioinformatics.intec.ugent.be/blsspeller
  
  
  BACKGROUND
  Klaas.Vandepoele@psb.vib-ugent.be or jan.fostier@intec.ugent.be.
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Department of Information Technology (INTEC), Ghent University-iMinds, Ghent, Belgium.
authors.forename: Dieter
authors.initials: D
authors.lastname: De Witte
authors.affiliation: Department of Plant Systems Biology, VIB and Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Van de Velde
authors.affiliation: Department of Information Technology (INTEC), Ghent University-iMinds, Ghent, Belgium.
authors.forename: Dries
authors.initials: D
authors.lastname: Decap
authors.affiliation: Department of Plant Systems Biology, VIB and Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, Belgium.
authors.forename: Michiel
authors.initials: M
authors.lastname: Van Bel
authors.affiliation: Department of Information Technology (INTEC), Ghent University-iMinds, Ghent, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Audenaert
authors.affiliation: Department of Information Technology (INTEC), Ghent University-iMinds, Ghent, Belgium.
authors.forename: Piet
authors.initials: P
authors.lastname: Demeester
authors.affiliation: Department of Information Technology (INTEC), Ghent University-iMinds, Ghent, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Dhoedt
authors.affiliation: Department of Plant Systems Biology, VIB and Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, Belgium.
authors.forename: Klaas
authors.initials: K
authors.lastname: Vandepoele
authors.affiliation: Department of Information Technology (INTEC), Ghent University-iMinds, Ghent, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Fostier
mesh_terms: D000465:Algorithms; D001483:Base Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D018744:DNA, Plant / Q000737:chemistry; D018745:Genome, Plant; D059372:Nucleotide Motifs; D011401:Promoter Regions, Genetic; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA / Q000379:methods*; D012984:Software; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D018744:DNA, Plant; D014157:Transcription Factors