Peak calling by Sparse Enrichment Analysis for CUT&RUN chromatin profiling
Peak calling by Sparse Enrichment Analysis for CUT&RUN chromatin profiling
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DOI：
10.1186/s13072-019-0287-4
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发表时间：
2019-07-12
影响因子：
3.9
通讯作者：
Henikoff, Steven
中科院分区：
文献类型：
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作者：
Meers, Michael P.;Tenenbaum, Dan;Henikoff, Steven
背景CUT&RUN是一种高效的表观基因组图谱分析方法，它在全基因组范围内识别DNA结合蛋白浓缩的位置，具有高信噪比和低测序要求。目前，切割和运行数据的分析非常复杂，这使得为分析芯片序列数据而设计的程序在识别蛋白质结合位点时容易出现过度敏感的情况。结果本文介绍了稀疏浓缩分析切割与运行分析(SEACR)，该分析策略利用背景信号的全球分布来校准峰值调用的简单阈值。SEACR从黄金标准CUT&RUN数据集中以近乎完美的特异性区分真阳性峰和假阳性峰，并有效地识别几个不同蛋白质目标的富集区。我们还引入了一个Web服务器(http://seacr.fredhutch.org)，用于即插即用分析和SEACR，它促进了所有技能水平的用户的最大可访问性。结论SEACR是一个高度选择性的峰值调用器，它最终验证了对具有已知真阴性的数据集的CUT&RUN的准确性。与现有的高峰呼叫策略相比，它的易用性和性能使其成为分析快速运行数据的理想选择。
BackgroundCUT&RUN is an efficient epigenome profiling method that identifies sites of DNA binding protein enrichment genome-wide with high signal to noise and low sequencing requirements. Currently, the analysis of CUT&RUN data is complicated by its exceptionally low background, which renders programs designed for analysis of ChIP-seq data vulnerable to oversensitivity in identifying sites of protein binding.ResultsHere we introduce Sparse Enrichment Analysis for CUT&RUN (SEACR), an analysis strategy that uses the global distribution of background signal to calibrate a simple threshold for peak calling. SEACR discriminates between true and false-positive peaks with near-perfect specificity from gold standard CUT&RUN datasets and efficiently identifies enriched regions for several different protein targets. We also introduce a web server(http://seacr.fredhutch.org) for plug-and-play analysis with SEACR that facilitates maximum accessibility across users of all skill levels.ConclusionsSEACR is a highly selective peak caller that definitively validates the accuracy of CUT&RUN for datasets with known true negatives. Its ease of use and performance in comparison with existing peak calling strategies make it an ideal choice for analyzing CUT&RUN data.