Detection of cooperatively bound transcription factor pairs using ChIP-seq peak intensities and expectation maximization
Detection of cooperatively bound transcription factor pairs using ChIP-seq peak intensities and expectation maximization
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DOI：
10.1371/journal.pone.0199771
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发表时间：
2018-07-17
期刊：
影响因子：
3.7
通讯作者：
Krishna, Sandeep
中科院分区：
文献类型：
--
作者：
Datta, Vishaka;Siddharthan, Rahul;Krishna, Sandeep
转录因子（TF）通常协同工作，其中一个TF与DNA的结合增强了第二个TF与附近位置的结合亲和力。这种协同结合对于在原核和真核细胞中激活启动子和增强子的基因表达是重要的。检测TF对的协同结合的现有方法依赖于分析结合的序列。我们提出了一种方法，该方法仅使用ChIP-seq峰强度和期望最大化（CPI-EM）算法。我们使用来自细胞的ChIP-seq数据来验证我们的方法，其中所考虑的一对TF中的一个已经被基因敲除。我们的算法依赖于我们的观察，即合作TFTF结合与其中一个TF的弱结合相关，我们在各种细胞类型中证明了这一点，包括E。coli、S. cerevisiae和M.肌细胞我们表明，这种方法比仅基于所考虑的TF的ChIP-seq峰距离的预测器表现得显著更好。这表明峰强度包含可以帮助检测TF对的协同结合的信息。CPI-EM在检测合作绑定方面也优于现有的基于序列的算法。CPI-EM算法可在https://github.com/vishakad/cpi-em上获得。
Transcription factors (TFs) often work cooperatively, where the binding of one TF to DNA enhances the binding affinity of a second TF to a nearby location. Such cooperative binding is important for activating gene expression from promoters and enhancers in both prokaryotic and eukaryotic cells. Existing methods to detect cooperative binding of a TF pair rely on analyzing the sequence that is bound. We propose a method that uses, instead, only ChlP-seq peak intensities and an expectation maximization (CPI-EM) algorithm. We validate our method using ChlP-seq data from cells where one of a pair of TFs under consideration has been genetically knocked out. Our algorithm relies on our observation that cooperative TFTF binding is correlated with weak binding of one of the TFs, which we demonstrate in a variety of cell types, including E. coli, S. cerevisiae and M. musculus cells. We show that this method performs significantly better than a predictor based only on the ChlP-seq peak distance of the TFs under consideration. This suggests that peak intensities contain information that can help detect the cooperative binding of a TF pair. CPI-EM also outperforms an existing sequence-based algorithm in detecting cooperative binding. The CPI-EM algorithm is available at https://github.com/vishakad/cpi-em.