title: Identification of C2H2-ZF binding preferences from ChIP-seq data using RCADE.
abstract: Current methods for motif discovery from chromatin immunoprecipitation followed by sequencing (ChIP-seq) data often identify non-targeted transcription factor (TF) motifs, and are even further limited when peak sequences are similar due to common ancestry rather than common binding factors. The latter aspect particularly affects a large number of proteins from the Cys2His2 zinc finger (C2H2-ZF) class of TFs, as their binding sites are often dominated by endogenous retroelements that have highly similar sequences. Here, we present recognition code-assisted discovery of regulatory elements (RCADE) for motif discovery from C2H2-ZF ChIP-seq data. RCADE combines predictions from a DNA recognition code of C2H2-ZFs with ChIP-seq data to identify models that represent the genuine DNA binding preferences of C2H2-ZF proteins. We show that RCADE is able to identify generalizable binding models even from peaks that are exclusively located within the repeat regions of the genome, where state-of-the-art motif finding approaches largely fail.
  
  
  METHODS
  RCADE is available as a webserver and also for download at http://rcade.ccbr.utoronto.ca/.
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
  
  
  BACKGROUND
  t.hughes@utoronto.ca.
authors.affiliation: Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.
authors.forename: Hamed S
authors.initials: HS
authors.lastname: Najafabadi
authors.affiliation: Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.
authors.forename: Mihai
authors.initials: M
authors.lastname: Albu
authors.affiliation: Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada and Canadian Institute for Advanced Research, Toronto, ON, Canada.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Hughes
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation / Q000379:methods*; D005786:Gene Expression Regulation; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D059372:Nucleotide Motifs / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins; D018626:Retroelements / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods; D014157:Transcription Factors / Q000378:metabolism*; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: C486563:BCL11A protein, human; D002352:Carrier Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D018626:Retroelements; D014157:Transcription Factors