Analysis of single-cell CRISPR perturbations indicates that enhancers predominantly act multiplicatively Journal Article


Authors: Zhou, J. L.; Guruvayurappan, K.; Toneyan, S.; Chen, H. V.; Chen, A. R.; Koo, P.; McVicker, G.
Article Title: Analysis of single-cell CRISPR perturbations indicates that enhancers predominantly act multiplicatively
Abstract: 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. © 2024 The Author(s)
Keywords: controlled study; human cell; nonhuman; mouse; gene expression; embryo; simulation; regulatory mechanism; computer model; statistical model; transcriptional regulation; enhancer region; etiology; false discovery rate; enhancers; human; article; crispr; clustered regularly interspaced short palindromic repeat; single-cell sequencing; statistical modeling; data simulation; generalized linear models; genome-wide crispr screen; regulatory screen
Journal Title: Cell Genomics
Volume: 4
Issue: 11
ISSN: 2666-979X
Publisher: Cell Press  
Date Published: 2024-11-13
Start Page: 100672
Language: English
DOI: 10.1016/j.xgen.2024.100672
PROVIDER: scopus
PMCID: PMC11605691
PUBMED: 39406234
DOI/URL:
Notes: Article -- Source: Scopus
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