CUT&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. Here 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. SEACR 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.

中文翻译：

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通过稀疏富集分析调用峰进行CUT＆RUN染色质分析。

CUT＆RUN是一种有效的表观基因组图谱分析方法，可在全基因组范围内鉴定具有高信噪比和低测序要求的DNA结合蛋白富集位点。当前，CUT＆RUN数据的分析由于其极低的背景而变得复杂，这使得设计用于分析ChIP-seq数据的程序容易受到对识别蛋白质结合位点的过度敏感性的影响。在这里，我们介绍了针对CUT＆RUN的稀疏富集分析（SEACR），一种使用背景信号的全局分布来校准用于峰调用的简单阈值的分析策略。SEACR通过“黄金标准” CUT＆RUN数据集以近乎完美的特异性区分真假峰和假阳性峰，并有效地鉴定了几种不同蛋白质靶标的富集区域。我们还引入了一个Web服务器（http://seacr.fredhutch.org），用于使用SEACR进行即插即用分析，该功能可促进所有技能水平的用户之间的最大可访问性。SEACR是一个高度选择性的峰调用程序，可以对具有已知真实负数的数据集进行绝对验证，以验证CUT＆RUN的准确性。与现有的峰值调用策略相比，它的易用性和性能使其成为分析CUT＆RUN数据的理想选择。