Evidence map›Paper›PMID 39406234›Full record

ArticleCell genomics2024

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

Jessica L Zhou, Karthik Guruvayurappan, Shushan Toneyan, Hsiuyi V Chen, Aaron R Chen, Peter Koo, Graham McVicker

Abstract read
In one paragraph

Article in Cell genomics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Jessica L ZhouIntegrative Biology Laboratory, Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA; Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA 92093, USA; Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Karthik GuruvayurappanIntegrative Biology Laboratory, Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA; School of Biological Sciences, University of California, San Diego, La Jolla, CA 92037, USA; Halicioglu Data Science Institute, University of California, San Diego, La Jolla, CA 92093, USA; Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Shushan ToneyanCold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Hsiuyi V ChenIntegrative Biology Laboratory, Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA.
Aaron R ChenIntegrative Biology Laboratory, Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA.
Peter KooCold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Graham McVickerIntegrative Biology Laboratory, Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: gmcvicker@salk.edu.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
Using genomic perturbations to understand trait-associated human genetic variationR35HG011315 · NHGRI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI MCVICKER, GRAHAM · 2021 to 2025
$2.9M
Computational analysis of single-nucleus sequencing data for studying the cell type-specific basis of opioid use disordersF31DA056226 · NIDA · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI ZHOU, JESSICA LU · 2022 to 2023
$68k
NCI NIH HHS P30 CA008748NHGRI NIH HHS R35 HG011315NIDA NIH HHS F31 DA056226
6 · The paper itself

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.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsEnhancer Elements, GeneticSingle-Cell AnalysisCRISPR-Cas SystemsHumansCRISPRdata simulationenhancersgene expressiongeneralized linear modelsgenome-wide CRISPR screenregulatory screensingle-cell sequencingstatistical modelingtranscriptional regulation

Identifiers

PMID39406234
PMCPMC11605691

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.