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首页> 外文期刊>BMC Veterinary Research >Pinpointing transcription factor binding sites from ChIP-seq data with SeqSite
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Pinpointing transcription factor binding sites from ChIP-seq data with SeqSite

机译：使用SeqSite精确定位ChIP-seq数据中的转录因子结合位点

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BackgroundChromatin immunoprecipitation combined with the next-generation DNA sequencing technologies (ChIP-seq) becomes a key approach for detecting genome-wide sets of genomic sites bound by proteins, such as transcription factors (TFs). Several methods and open-source tools have been developed to analyze ChIP-seq data. However, most of them are designed for detecting TF binding regions instead of accurately locating transcription factor binding sites (TFBSs). It is still challenging to pinpoint TFBSs directly from ChIP-seq data, especially in regions with closely spaced binding events.ResultsWith the aim to pinpoint TFBSs at a high resolution, we propose a novel method named SeqSite, implementing a two-step strategy: detecting tag-enriched regions first and pinpointing binding sites in the detected regions. The second step is done by modeling the tag density profile, locating TFBSs on each strand with a least-squares model fitting strategy, and merging the detections from the two strands. Experiments on simulation data show that SeqSite can locate most of the binding sites more than 40-bp from each other. Applications on three human TF ChIP-seq datasets demonstrate the advantage of SeqSite for its higher resolution in pinpointing binding sites compared with existing methods.ConclusionsWe have developed a computational tool named SeqSite, which can pinpoint both closely spaced and isolated binding sites, and consequently improves the resolution of TFBS detection from ChIP-seq data.
机译：背景染色质免疫沉淀与下一代DNA测序技术（ChIP-seq）结合成为检测由蛋白质结合的全基因组基因组位点的关键方法，例如转录因子（TFs）。已经开发了几种方法和开源工具来分析ChIP-seq数据。但是，大多数设计用于检测TF结合区域，而不是准确定位转录因子结合位点（TFBS）。直接从ChIP-seq数据中精确定位TFBS仍然具有挑战性，尤其是在具有紧密间隔的结合事件的区域中。结果为了以高分辨率精确定位TFBS，我们提出了一种名为SeqSite的新颖方法，该方法实现了两步策略：检测标签富集区域首先定位在检测区域中的结合位点。第二步是通过对标签密度分布进行建模，使用最小二乘模型拟合策略在每条链上定位TFBS以及合并两条链的检测结果来完成的。仿真数据实验表明，SeqSite可以定位彼此之间超过40 bp的大多数结合位点。在三个人类TF ChIP-seq数据集上的应用表明，与现有方法相比，SeqSite在确定结合位点上具有更高的分辨率。 ChIP-seq数据中TFBS检测的分辨率。

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