title: Genome-wide histone acetylation data improve prediction of mammalian transcription factor binding sites.
abstract: BACKGROUND
  Histone acetylation (HAc) is associated with open chromatin, and HAc has been shown to facilitate transcription factor (TF) binding in mammalian cells. In the innate immune system context, epigenetic studies strongly implicate HAc in the transcriptional response of activated macrophages. We hypothesized that using data from large-scale sequencing of a HAc chromatin immunoprecipitation assay (ChIP-Seq) would improve the performance of computational prediction of binding locations of TFs mediating the response to a signaling event, namely, macrophage activation.
  
  
  RESULTS
  We tested this hypothesis using a multi-evidence approach for predicting binding sites. As a training/test dataset, we used ChIP-Seq-derived TF binding site locations for five TFs in activated murine macrophages. Our model combined TF binding site motif scanning with evidence from sequence-based sources and from HAc ChIP-Seq data, using a weighted sum of thresholded scores. We find that using HAc data significantly improves the performance of motif-based TF binding site prediction. Furthermore, we find that within regions of high HAc, local minima of the HAc ChIP-Seq signal are particularly strongly correlated with TF binding locations. Our model, using motif scanning and HAc local minima, improves the sensitivity for TF binding site prediction by approximately 50% over a model based on motif scanning alone, at a false positive rate cutoff of 0.01.
  
  
  BACKGROUND
  The data and software source code for model training and validation are freely available online at http://magnet.systemsbiology.net/hac.
authors.affiliation: Institute for Systems Biology, 1441 North 34th Street, Seattle, WA 98103, USA. aderem@systemsbiology.org
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Ramsey
authors.forename: Theo A
authors.initials: TA
authors.lastname: Knijnenburg
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Kennedy
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Zak
authors.forename: Mark
authors.initials: M
authors.lastname: Gilchrist
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Gold
authors.forename: Carrie D
authors.initials: CD
authors.lastname: Johnson
authors.forename: Aaron E
authors.initials: AE
authors.lastname: Lampano
authors.forename: Vladimir
authors.initials: V
authors.lastname: Litvak
authors.forename: Garnet
authors.initials: G
authors.lastname: Navarro
authors.forename: Tetyana
authors.initials: T
authors.lastname: Stolyar
authors.forename: Alan
authors.initials: A
authors.lastname: Aderem
authors.forename: Ilya
authors.initials: I
authors.lastname: Shmulevich
mesh_terms: D000107:Acetylation; D000818:Animals; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation / Q000379:methods*; D016678:Genome; D006657:Histones / Q000378:metabolism; D008262:Macrophage Activation; D051379:Mice; D008954:Models, Biological; D012984:Software; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D006657:Histones; D014157:Transcription Factors