对单细胞CRISPR扰动的分析表明,增强子主要起倍增作用。

IF 11.1 Q1 CELL BIOLOGY Cell genomics Pub Date : 2024-11-13 Epub Date: 2024-10-14 DOI:10.1016/j.xgen.2024.100672
Jessica L Zhou, Karthik Guruvayurappan, Shushan Toneyan, Hsiuyi V Chen, Aaron R Chen, Peter Koo, Graham McVicker
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引用次数: 0

摘要

一个基因可能有多个增强子,但人们对它们如何协同调节转录却知之甚少。为了分析增强子在整个基因组中的相互作用,我们开发了一个广义线性建模框架 GLiMMIRS,用于分析单细胞 CRISPR 实验中的增强子效应。我们将 GLiMMIRS 应用于已发表的数据集,测试了 46,166 个增强子对和相应基因之间的相互作用,其中包括 264 个 "高置信度 "增强子对。我们发现,增强子效应是成倍结合的,但进一步相互作用的证据有限。只有 31 个增强子对表现出显著的相互作用(假发现率
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Analysis of single-cell CRISPR perturbations indicates that enhancers predominantly act multiplicatively.

A single gene may have multiple enhancers, but how they work in concert to regulate transcription is poorly understood. To analyze enhancer interactions throughout the genome, we developed a generalized linear modeling framework, GLiMMIRS, for interrogating enhancer effects from single-cell CRISPR experiments. We applied GLiMMIRS to a published dataset and tested for interactions between 46,166 enhancer pairs and corresponding genes, including 264 "high-confidence" enhancer pairs. We found that enhancer effects combine multiplicatively but with limited evidence for further interactions. Only 31 enhancer pairs exhibited significant interactions (false discovery rate <0.1), none of which came from the high-confidence set, and 20 were driven by outlier expression values. Additional analyses of a second CRISPR dataset and in silico enhancer perturbations with Enformer both support a multiplicative model of enhancer effects without interactions. Altogether, our results indicate that enhancer interactions are uncommon or have small effects that are difficult to detect.

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