title: MCAST: scanning for cis-regulatory motif clusters.
abstract: Precise regulatory control of genes, particularly in eukaryotes, frequently requires the joint action of multiple sequence-specific transcription factors. A cis-regulatory module (CRM) is a genomic locus that is responsible for gene regulation and that contains multiple transcription factor binding sites in close proximity. Given a collection of known transcription factor binding motifs, many bioinformatics methods have been proposed over the past 15 years for identifying within a genomic sequence candidate CRMs consisting of clusters of those motifs.
  
  
  
  The MCAST algorithm uses a hidden Markov model with a P-value-based scoring scheme to identify candidate CRMs. Here, we introduce a new version of MCAST that offers improved graphical output, a dynamic background model, statistical confidence estimates based on false discovery rate estimation and, most significantly, the ability to predict CRMs while taking into account epigenomic data such as DNase I sensitivity or histone modification data. We demonstrate the validity of MCAST's statistical confidence estimates and the utility of epigenomic priors in identifying CRMs.
  
  
  
  MCAST is part of the MEME Suite software toolkit. A web server and source code are available at http://meme-suite.org and http://alternate.meme-suite.org
  
  
  
  t.bailey@imb.uq.edu.au or william-noble@uw.edu
  
  
  
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA, USA.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Grant
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia and.
authors.forename: James
authors.initials: J
authors.lastname: Johnson
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia and.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Bailey
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA, USA, Department of Computer Science and Engineering, University of Washington, Seattle, WA, USA.
authors.forename: William Stafford
authors.initials: WS
authors.lastname: Noble
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D016678:Genome; D006801:Humans; D050436:Regulatory Elements, Transcriptional; D017422:Sequence Analysis, DNA; D012984:Software; D014157:Transcription Factors
chemical_list: D014157:Transcription Factors