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基因表达中的转录爆发动力学。

Transcriptional bursting dynamics in gene expression.

作者信息

Zhang Qiuyu, Cao Wenjie, Wang Jiaqi, Yin Yihao, Sun Rui, Tian Zunyi, Hu Yuhan, Tan Yalan, Zhang Ben-Gong

机构信息

Research Center of Nonlinear Sciences, School of Mathematical & Physical Sciences, Wuhan Textile University, Wu Han, China.

School of Mathematics, Sun Yat-sen University, Guangzhou, China.

出版信息

Front Genet. 2024 Sep 13;15:1451461. doi: 10.3389/fgene.2024.1451461. eCollection 2024.

Abstract

Gene transcription is a stochastic process that occurs in all organisms. Transcriptional bursting, a critical molecular dynamics mechanism, creates significant heterogeneity in mRNA and protein levels. This heterogeneity drives cellular phenotypic diversity. Currently, the lack of a comprehensive quantitative model limits the research on transcriptional bursting. This review examines various gene expression models and compares their strengths and weaknesses to guide researchers in selecting the most suitable model for their research context. We also provide a detailed summary of the key metrics related to transcriptional bursting. We compared the temporal dynamics of transcriptional bursting across species and the molecular mechanisms influencing these bursts, and highlighted the spatiotemporal patterns of gene expression differences by utilizing metrics such as burst size and burst frequency. We summarized the strategies for modeling gene expression from both biostatistical and biochemical reaction network perspectives. Single-cell sequencing data and integrated multiomics approaches drive our exploration of cutting-edge trends in transcriptional bursting mechanisms. Moreover, we examined classical methods for parameter estimation that help capture dynamic parameters in gene expression data, assessing their merits and limitations to facilitate optimal parameter estimation. Our comprehensive summary and review of the current transcriptional burst dynamics theories provide deeper insights for promoting research on the nature of cell processes, cell fate determination, and cancer diagnosis.

摘要

基因转录是一个在所有生物体中都会发生的随机过程。转录爆发是一种关键的分子动力学机制,它在mRNA和蛋白质水平上产生显著的异质性。这种异质性驱动了细胞表型的多样性。目前,缺乏一个全面的定量模型限制了对转录爆发的研究。这篇综述考察了各种基因表达模型,并比较了它们的优缺点,以指导研究人员为其研究背景选择最合适的模型。我们还提供了与转录爆发相关的关键指标的详细总结。我们比较了不同物种间转录爆发的时间动态以及影响这些爆发的分子机制,并通过利用爆发大小和爆发频率等指标突出了基因表达差异的时空模式。我们从生物统计学和生化反应网络的角度总结了基因表达建模的策略。单细胞测序数据和整合多组学方法推动了我们对转录爆发机制前沿趋势的探索。此外,我们考察了有助于捕捉基因表达数据中动态参数的经典参数估计方法,评估了它们的优缺点以促进最佳参数估计。我们对当前转录爆发动力学理论的全面总结和综述为推动细胞过程本质、细胞命运决定和癌症诊断的研究提供了更深入的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0475/11437526/dd0b72db9e5e/fgene-15-1451461-g001.jpg

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