title: Tissue-specific prediction of directly regulated genes.
abstract: Direct binding by a transcription factor (TF) to the proximal promoter of a gene is a strong evidence that the TF regulates the gene. Assaying the genome-wide binding of every TF in every cell type and condition is currently impractical. Histone modifications correlate with tissue/cell/condition-specific ('tissue specific') TF binding, so histone ChIP-seq data can be combined with traditional position weight matrix (PWM) methods to make tissue-specific predictions of TF-promoter interactions.
  
  
  RESULTS
  We use supervised learning to train a naïve Bayes predictor of TF-promoter binding. The predictor's features are the histone modification levels and a PWM-based score for the promoter. Training and testing uses sets of promoters labeled using TF ChIP-seq data, and we use cross-validation on 23 such datasets to measure the accuracy. A PWM+histone naïve Bayes predictor using a single histone modification (H3K4me3) is substantially more accurate than a PWM score or a conservation-based score (phylogenetic motif model). The naïve Bayes predictor is more accurate (on average) at all sensitivity levels, and makes only half as many false positive predictions at sensitivity levels from 10% to 80%. On average, it correctly predicts 80% of bound promoters at a false positive rate of 20%. Accuracy does not diminish when we test the predictor in a different cell type (and species) from training. Accuracy is barely diminished even when we train the predictor without using TF ChIP-seq data.
  
  
  BACKGROUND
  Our tissue-specific predictor of promoters bound by a TF is called Dr Gene and is available at http://bioinformatics.org.au/drgene.
  
  
  BACKGROUND
  t.bailey@imb.uq.edu.au
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors: Robert C
authors: RC
authors: McLeay
authors: Chris J
authors: CJ
authors: Leat
authors: Timothy L
authors: TL
authors: Bailey
mesh_terms: D001499:Bayes Theorem; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D014157:Transcription Factors