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Synergising single-cell resolution and 4sU labelling boosts inference of transcriptional bursting
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Edwards, David M., Davies, Philip and Hebenstreit, Daniel (2023) Synergising single-cell resolution and 4sU labelling boosts inference of transcriptional bursting. Genome Biology, 24 . 138 . doi:10.1186/s13059-023-02977-y ISSN 1474-7596.
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Official URL: https://doi.org/10.1186/s13059-023-02977-y
Abstract
Despite the recent rise of RNA-seq datasets combining single-cell (sc) resolution with 4-thiouridine (4sU) labelling, analytical methods exploiting their power to dissect transcriptional bursting are lacking. Here, we present a mathematical model and Bayesian inference implementation to facilitate genome-wide joint parameter estimation and confidence quantification (R package: burstMCMC). We demonstrate that, unlike conventional scRNA-seq, 4sU scRNA-seq resolves temporal parameters and furthermore boosts inference of dimensionless parameters via a synergy between single-cell resolution and 4sU labelling. We apply our method to published 4sU scRNA-seq data and linked with ChIP-seq data, we uncover previously obscured associations between different parameters and histone modifications.
Item Type: | Journal Article | |||||||||
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Subjects: | Q Science > QH Natural history > QH426 Genetics Q Science > QP Physiology |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | |||||||||
Library of Congress Subject Headings (LCSH): | RNA, Genetic regulation, Transcription factors, Genetic transcription -- Regulation, RNA polymerases | |||||||||
Journal or Publication Title: | Genome Biology | |||||||||
Publisher: | BioMed Central Ltd. | |||||||||
ISSN: | 1474-7596 | |||||||||
Official Date: | 16 June 2023 | |||||||||
Dates: |
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Volume: | 24 | |||||||||
Article Number: | 138 | |||||||||
DOI: | 10.1186/s13059-023-02977-y | |||||||||
Status: | Peer Reviewed | |||||||||
Publication Status: | Published | |||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||
Date of first compliant deposit: | 5 May 2023 | |||||||||
Date of first compliant Open Access: | 19 June 2023 | |||||||||
RIOXX Funder/Project Grant: |
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