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Genome-wide histone acetylation data improve prediction of mammalian transcription factor binding sites
- Source :
- Bioinformatics
- Publication Year :
- 2010
- Publisher :
- Oxford University Press, 2010.
-
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 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 ∼50% over a model based on motif scanning alone, at a false positive rate cutoff of 0.01. Availability: The data and software source code for model training and validation are freely available online at http://magnet.systemsbiology.net/hac. Contact: aderem@systemsbiology.org; ishmulevich@systemsbiology.org Supplementary information: Supplementary data are available at Bioinformatics online.
- Subjects :
- Statistics and Probability
Chromatin Immunoprecipitation
Computational biology
Biology
Biochemistry
Models, Biological
Histones
03 medical and health sciences
Mice
0302 clinical medicine
Transcription (biology)
Animals
natural sciences
Binding site
Molecular Biology
Transcription factor
030304 developmental biology
Genetics
0303 health sciences
Binding Sites
Genome
Acetylation
Macrophage Activation
Genome Analysis
3. Good health
Computer Science Applications
Chromatin
DNA binding site
Computational Mathematics
Discovery Note
Histone
Computational Theory and Mathematics
030220 oncology & carcinogenesis
biology.protein
Chromatin immunoprecipitation
Software
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 13674811 and 13674803
- Volume :
- 26
- Issue :
- 17
- Database :
- OpenAIRE
- Journal :
- Bioinformatics
- Accession number :
- edsair.doi.dedup.....07b8916aed98443b44c4c4ece71cd8b6