Zhou, Jessica, Guruvayurappan, Karthik, Toneyan, Shushan, Chen, Hsiuyi V, Chen, Aaron R, Koo, Peter, McVicker, Graham (July 2024) Analysis of single-cell CRISPR perturbations indicates that enhancers act multiplicatively and provides limited evidence for epistatic-like interactions. bioRxiv. (Public Dataset) (Submitted)
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10.1101.2023.04.26.538501.pdf - Submitted Version Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (19MB) | Preview |
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 (FDR < 0.1), of which none came from the high confidence subset 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.
| Item Type: | Paper |
|---|---|
| Subjects: | bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics Investigative techniques and equipment Investigative techniques and equipment > assays Investigative techniques and equipment > CRISPR-Cas9 Investigative techniques and equipment > assays > Single cell sequencing |
| CSHL Authors: | |
| Communities: | CSHL labs > Koo Lab |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 9 July 2024 |
| Date Deposited: | 02 Aug 2024 18:01 |
| Last Modified: | 02 Aug 2024 18:01 |
| PMCID: | PMC10168320 |
| Related URLs: | |
| Dataset ID: |
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| URI: | https://repository.cshl.edu/id/eprint/41628 |
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