Synergising single-cell resolution and 4sU labelling boosts inference of transcriptional bursting

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 g...

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Veröffentlicht in:Genome Biology Jg. 24; H. 1; S. 138
Hauptverfasser: Edwards, David M., Davies, Philip, Hebenstreit, Daniel
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London BioMed Central 16.06.2023
Springer Nature B.V
BMC
Schlagworte:
4sU
Animal Genetics and Genomics
Bayes Theorem
Bayesian analysis
Bayesian theory
Bioinformatics
Biomedical and Life Sciences
Bursting
Cell cycle
chromatin immunoprecipitation
Chromatin Immunoprecipitation Sequencing
data collection
Dynamics
Estimates
Evolutionary Biology
Genes
genome
Genomes
Histones
Human Genetics
Inference
Labeling
Life Sciences
Mathematical models
Method
Microbial Genetics and Genomics
Plant Genetics and Genomics
RNA polymerase
RNA-Seq
sequence analysis
Staining and Labeling
Thiouridine
Time-resolved
Transcription
transcription (genetics)
Transcription
Dynamics
4sU
Inference
Histone modification
Genome-wide
Bursting
Time-resolved
Single-cell
ISSN:1474-760X, 1474-7596, 1474-760X
Online-Zugang:Volltext
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Beschreibung
Zusammenfassung: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.
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ISSN:1474-760X
1474-7596
1474-760X
DOI:10.1186/s13059-023-02977-y