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转录爆发使toggle switch 的行为多样化:随机基因表达的混合模拟。

Transcriptional bursting diversifies the behaviour of a toggle switch: hybrid simulation of stochastic gene expression.

机构信息

Department of Applied Mathematics and Statistics, Comenius University, Mlynská dolina, Bratislava 842 48, Slovakia.

出版信息

Bull Math Biol. 2013 Feb;75(2):351-71. doi: 10.1007/s11538-013-9811-z. Epub 2013 Jan 25.

Abstract

Hybrid models for gene expression combine stochastic and deterministic representations of the underlying biophysical mechanisms. According to one of the simplest hybrid formalisms, protein molecules are produced in randomly occurring bursts of a randomly distributed size while they are degraded deterministically. Here, we use this particular formalism to study two key regulatory motifs-the autoregulation loop and the toggle switch. The distribution of burst times is determined and used as a basis for the development of exact simulation algorithms for gene expression dynamics. For the autoregulation loop, the simulations are compared to an analytic solution of a master equation. Simulations of the toggle switch reveal a number of qualitatively distinct scenarios with implications for the modelling of cell-fate selection.

摘要

混合模型用于基因表达,将潜在的生物物理机制的随机和确定表示结合在一起。根据最简单的混合形式之一,蛋白质分子在随机分布大小的随机突发中产生,而它们则确定性降解。在这里,我们使用这种特殊的形式来研究两个关键的调控模体 - 自调节环和切换开关。突发时间的分布是确定的,并用作基因表达动力学的精确模拟算法的基础。对于自调节环,模拟与主方程的解析解进行了比较。切换开关的模拟揭示了一些具有细胞命运选择建模意义的定性不同的情况。

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