Identification of transcription factor binding sites from ChIP-seq data at high resolution
Identification of transcription factor binding sites from ChIP-seq data at high resolution
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DOI：
10.1093/bioinformatics/btt470
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发表时间：
2013-11-01
期刊：
影响因子：
5.8
通讯作者：
Stark, Alexander
中科院分区：
文献类型：
--
作者：
Bardet, Anais F.;Steinmann, Jonas;Stark, Alexander
动机：染色质免疫沉淀结合下一代测序（ChIP-seq）被广泛用于研究转录因子（TF）及其调控靶点的体内结合位点。最近的改进ChIP-seq，如提高分辨率，承诺更深入地了解转录调控，但需要新的计算工具，以充分利用其优势。e.解析单个结合位点，即使间隔很近），正如我们使用半合成数据集，在具有不同实验片段大小的果蝇胚胎中对TF Twist进行ChIP-seq，并分析ChIP-exo数据集所证明的那样。我们发现，peakzilla达到的分辨率增加是高度相关的，因为紧密间隔的Twist结合位点在转录增强子中强烈富集，这表明了区分功能性和丰富的非功能性或中性TF结合的特征。Peakzilla易于使用，因为它可以从数据中估计所有必要的参数，并且可以免费获得。
Motivation: Chromatin immunoprecipitation coupled to next-generation sequencing (ChIP-seq) is widely used to study the in vivo binding sites of transcription factors (TFs) and their regulatory targets. Recent improvements to ChIP-seq, such as increased resolution, promise deeper insights into transcriptional regulation, yet require novel computational tools to fully leverage their advantages.Results: To this aim, we have developed peakzilla, which can identify closely spaced TF binding sites at high resolution (i. e. resolves individual binding sites even if spaced closely), as we demonstrate using semisynthetic datasets, performing ChIP-seq for the TF Twist in Drosophila embryos with different experimental fragment sizes, and analyzing ChIP-exo datasets. We show that the increased resolution reached by peakzilla is highly relevant, as closely spaced Twist binding sites are strongly enriched in transcriptional enhancers, suggesting a signature to discriminate functional from abundant non-functional or neutral TF binding. Peakzilla is easy to use, as it estimates all the necessary parameters from the data and is freely available.