Correcting signal biases and detecting regulatory elements in STARR-seq data.

Correcting signal biases and detecting regulatory elements in STARR-seq data.
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DOI:
10.1101/gr.269209.120
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发表时间:
2021-05
期刊:
影响因子:
7
通讯作者:
Reddy TE
Reddy TE
中科院分区:
生物学1区
文献类型:
--
作者:
Kim YS;Johnson GD;Seo J;Barrera A;Cowart TN;Majoros WH;Ochoa A;Allen AS;Reddy TE

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自转录活性调控区测序(STARR-seq)等高通量报告基因测定法已经可以一次测量整个人类基因组中的调控元件活性。然而,由此产生的数据提出了重大的分析挑战。在这里,我们确定了解释STARR-seq数据中大部分方差的技术偏差。然后,我们开发了一个统计模型,以纠正这些偏见,并提高监管要素的检测。这种方法大大提高了当前方法的精确度和召回率,提高了激活和抑制调节元件的检测,并控制了错误的发现,尽管在信号中存在很强的局部相关性。
High-throughput reporter assays such as self-transcribing active regulatory region sequencing (STARR-seq) have made it possible to measure regulatory element activity across the entire human genome at once. The resulting data, however, present substantial analytical challenges. Here, we identify technical biases that explain most of the variance in STARR-seq data. We then develop a statistical model to correct those biases and to improve detection of regulatory elements. This approach substantially improves precision and recall over current methods, improves detection of both activating and repressive regulatory elements, and controls for false discoveries despite strong local correlations in signal.
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