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 e...

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Bibliographic Details
Published in:Cell genomics 2024-11, Vol.4 (11), p.100672, Article 100672
Main Authors: Zhou, Jessica L., Guruvayurappan, Karthik, Toneyan, Shushan, Chen, Hsiuyi V., Chen, Aaron R., Koo, Peter, McVicker, Graham
Format: Article
Language:English
Subjects:
Clustered Regularly Interspaced Short Palindromic Repeats - genetics
CRISPR
CRISPR-Cas Systems - genetics
data simulation
Enhancer Elements, Genetic - genetics
enhancers
gene expression
generalized linear models
genome-wide CRISPR screen
Humans
regulatory screen
Single-Cell Analysis
single-cell sequencing
statistical modeling
Technology
transcriptional regulation
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Summary: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
ISSN:2666-979X
2666-979X
DOI:10.1016/j.xgen.2024.100672