title: Predicting the binding preference of transcription factors to individual DNA k-mers.
abstract: BACKGROUND
  Recognition of specific DNA sequences is a central mechanism by which transcription factors (TFs) control gene expression. Many TF-binding preferences, however, are unknown or poorly characterized, in part due to the difficulty associated with determining their specificity experimentally, and an incomplete understanding of the mechanisms governing sequence specificity. New techniques that estimate the affinity of TFs to all possible k-mers provide a new opportunity to study DNA-protein interaction mechanisms, and may facilitate inference of binding preferences for members of a given TF family when such information is available for other family members.
  
  
  RESULTS
  We employed a new dataset consisting of the relative preferences of mouse homeodomains for all eight-base DNA sequences in order to ask how well we can predict the binding profiles of homeodomains when only their protein sequences are given. We evaluated a panel of standard statistical inference techniques, as well as variations of the protein features considered. Nearest neighbour among functionally important residues emerged among the most effective methods. Our results underscore the complexity of TF-DNA recognition, and suggest a rational approach for future analyses of TF families.
authors.affiliation: Department of Molecular Genetics, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada.
authors.forename: Trevis M
authors.initials: TM
authors.lastname: Alleyne
authors.forename: Lourdes
authors.initials: L
authors.lastname: Peña-Castillo
authors.forename: Gwenael
authors.initials: G
authors.lastname: Badis
authors.forename: Shaheynoor
authors.initials: S
authors.lastname: Talukder
authors.forename: Michael F
authors.initials: MF
authors.lastname: Berger
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Gehrke
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Philippakis
authors.forename: Martha L
authors.initials: ML
authors.lastname: Bulyk
authors.forename: Quaid D
authors.initials: QD
authors.lastname: Morris
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Hughes
mesh_terms: D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D017422:Sequence Analysis, DNA / Q000379:methods*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D014157:Transcription Factors; D004247:DNA