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具有纤维化对称性的遗传回路中的动力学与分岔

Dynamics and bifurcations in genetic circuits with fibration symmetries.

作者信息

Stewart Ian, Reis Saulo D S, Makse Hernán A

机构信息

Mathematics Institute, University of Warwick , Coventry CV4 7AL, UK.

Departamento de Física, Universidade Federal do Ceará , Fortaleza, Ceará, Brazil.

出版信息

J R Soc Interface. 2024 Aug;21(217):20240386. doi: 10.1098/rsif.2024.0386. Epub 2024 Aug 14.

Abstract

Circuit building blocks of gene regulatory networks (GRN) have been identified through the fibration symmetries of the underlying biological graph. Here, we analyse analytically six of these circuits that occur as functional and synchronous building blocks in these networks. Of these, the lock-on, toggle switch, Smolen oscillator, feed-forward fibre and Fibonacci fibre circuits occur in living organisms, notably ; the sixth, the repressilator, is a synthetic GRN. We consider synchronous steady states determined by a fibration symmetry (or balanced colouring) and determine analytic conditions for local bifurcation from such states, which can in principle be either steady-state or Hopf bifurcations. We identify conditions that characterize the first bifurcation, the only one that can be stable near the bifurcation point. We model the state of each gene in terms of two variables: mRNA and protein concentration. We consider all possible 'admissible' models-those compatible with the network structure-and then specialize these general results to simple models based on Hill functions and linear degradation. The results systematically classify using graph symmetries the complexity and dynamics of these circuits, which are relevant to understand the functionality of natural and synthetic cells.

摘要

基因调控网络(GRN)的电路构建模块已通过基础生物图的纤维化对称性得以识别。在此,我们对这些电路中的六个进行分析,它们在这些网络中作为功能性和同步性的构建模块出现。其中,锁定、拨动开关、斯莫伦振荡器、前馈纤维和斐波那契纤维电路存在于生物体中,特别是;第六个,即抑制器,是一种合成基因调控网络。我们考虑由纤维化对称性(或平衡着色)确定的同步稳态,并确定从此类状态发生局部分岔的解析条件,原则上这些分岔可以是稳态分岔或霍普夫分岔。我们确定了表征第一个分岔的条件,这是在分岔点附近唯一可能稳定的分岔。我们用两个变量来描述每个基因的状态:信使核糖核酸(mRNA)和蛋白质浓度。我们考虑所有可能的“可接受”模型——那些与网络结构兼容的模型——然后将这些一般结果专门应用于基于希尔函数和线性降解的简单模型上。这些结果利用图对称性系统地对这些电路的复杂性和动力学进行分类,这对于理解天然细胞和合成细胞的功能至关重要。

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