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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Vydáno v:	Genome Biology Ročník 24; číslo 1; s. 138
Hlavní autoři:	Edwards, David M., Davies, Philip, Hebenstreit, Daniel
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London BioMed Central 16.06.2023 Springer Nature B.V BMC
Témata:	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
On-line přístup:	Získat plný text
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1474-760X 1474-7596 1474-760X
DOI:	10.1186/s13059-023-02977-y