Genome-wide histone acetylation data improve prediction of mammalian transcription factor binding sites

• DOI: 10.1093/bioinformatics/btq405
• Publication Date: 2010-07-28T00:49:19Z
• Authors: Stephen A. Ramsey; Theo A. Knijnenburg; Kathleen A. Kennedy; Daniel E. Zak; Mark Gilchrist; Elizabeth S. Gold; Carrie D. Johnson; Aaron E. Lampano; Vladimir Litvak; Garnet Navarro; Tetyana Stolyar; Alan Aderem; Ilya Shmulevich
• Keywords: Chromatin immunoprecipitation; Sequence motif; DNA binding site; Motif (music)

Abstract Motivation: 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 transcriptional response of activated macrophages. We hypothesized that using data from large-scale sequencing a chromatin immunoprecipitation assay (ChIP-Seq) would improve performance computational prediction locations TFs mediating signaling event, namely, macrophage activation. Results: tested this hypothesis multi-evidence approach for predicting sites. As training/test dataset, we used ChIP-Seq-derived TF site five murine Our model combined motif scanning evidence sequence-based sources ChIP-Seq data, weighted sum thresholded scores. find significantly improves motif-based prediction. Furthermore, within regions high HAc, local minima signal are particularly correlated locations. model, minima, sensitivity by ∼50% over based on alone, at false positive rate cutoff 0.01. Availability: The software source code training validation freely available online http://magnet.systemsbiology.net/hac. Contact: [e-mail]; [e-mail] Supplementary information: Bioinformatics online.