title: A DNA shape-based regulatory score improves position-weight matrix-based recognition of transcription factor binding sites.
abstract: BACKGROUND
  The position-weight matrix (PWM) is a useful representation of a transcription factor binding site (TFBS) sequence pattern because the PWM can be estimated from a small number of representative TFBS sequences. However, because the PWM probability model assumes independence between individual nucleotide positions, the PWMs for some TFs poorly discriminate binding sites from non-binding-sites that have similar sequence content. Since the local three-dimensional DNA structure ('shape') is a determinant of TF binding specificity and since DNA shape has a significant sequence-dependence, we combined DNA shape-derived features into a TF-generalized regulatory score and tested whether the score could improve PWM-based discrimination of TFBS from non-binding-sites.
  
  
  RESULTS
  We compared a traditional PWM model to a model that combines the PWM with a DNA shape feature-based regulatory potential score, for accuracy in detecting binding sites for 75 vertebrate transcription factors. The PWM+shape model was more accurate than the PWM-only model, for 45% of TFs tested, with no significant loss of accuracy for the remaining TFs.
  
  
  METHODS
  The shape-based model is available as an open-source R package at that is archived on the GitHub software repository at https://github.com/ramseylab/regshape/.
  
  
  BACKGROUND
  stephen.ramsey@oregonstate.edu
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Department of Biomedical Sciences and.
authors.forename: Jichen
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Biomedical Sciences and School of Electrical Engineering and Computer Science, Oregon State University, Corvallis, OR, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Ramsey
mesh_terms: D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008962:Models, Theoretical; D056510:Position-Specific Scoring Matrices; D011485:Protein Binding; D012984:Software; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D014157:Transcription Factors; D004247:DNA