文章基本信息

标题：Modeling noise propagation in time-delayed auto-inhibitory genetic circuits
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作者：Zhanhao Zhang ; Supravat Dey ; Abhyudai Singh 等
期刊名称：IFAC PapersOnLine
印刷版ISSN：2405-8963
出版年度：2022
卷号：55
期号：20
页码：552-557
DOI：10.1016/j.ifacol.2022.09.153
语种：English
出版社：Elsevier
摘要：AbstractThe abundance of specific protein molecules in genetically identical cell populations exposed to the same external environment can show remarkable cell-to-cell variations as biochemical reactions are inherently stochastic and occur with low numbers of molecular copies. Such variations in gene products are commonly known as gene expression noise. One of the mechanisms for cells to reduce such noise is auto-regulatory negative feedback (auto-inhibition), commonly found across organisms. This auto-inhibition is subjected to unavoidable time-delays associated with transcriptional and translational processes. Sufficient time-delays and strong auto-inhibition can generate sustained oscillations in gene products, which is a common mechanism for precise timekeeping in many biomolecular clocks. While the importance of time-delays in the generation of oscillations is well appreciated, its role in stochastic dynamics is not well understood in the absence of sustained oscillations. Here, we investigate the interplay between the feedback strength and the time-delay to study the noise propagation in the non-oscillatory regime using linear stability analysis, the linear noise approximation, and stochastic simulations. From a simple auto-regulatory model with one protein species (no delay), we systematically introduce one-step and two-step time-delays by incorporating intermediate dynamics with additional second and third species, respectively. Interestingly, the negative feedback in the presence of time-delay can show counterintuitive noise behavior to our common perception about its role as a noise buffer.
关键词：KeywordsStochastic systemTime-delayGene expresion noiseMoment analysisSystem biology