Sun Yanhong, Zhang Fengyu, Ouyang Qi, Luo Chunxiong
The State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing 100871, China.
Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
iScience. 2024 Feb 5;27(3):109142. doi: 10.1016/j.isci.2024.109142. eCollection 2024 Mar 15.
Differential equation models are widely used to describe genetic regulations, predict multicomponent regulatory circuits, and provide quantitative insights. However, it is still challenging to quantitatively link the dynamic behaviors with measured parameters in synthetic circuits. Here, we propose a dynamic delay model (DDM) which includes two simple parts: the dynamic determining part and the doses-related steady-state-determining part. The dynamic determining part is usually supposed as the delay time but without a clear formula. For the first time, we give the detail formula of the dynamic determining function and provide a method for measuring all parameters of synthetic elements (include 8 activators and 5 repressors) by microfluidic system. Three synthetic circuits were built to show that the DDM can notably improve the prediction accuracy and can be used in various synthetic biology applications.
微分方程模型被广泛用于描述基因调控、预测多组分调控回路并提供定量见解。然而,在合成回路中,将动态行为与测量参数进行定量关联仍然具有挑战性。在此,我们提出了一种动态延迟模型(DDM),它包括两个简单部分:动态决定部分和与剂量相关的稳态决定部分。动态决定部分通常被认为是延迟时间,但没有明确的公式。我们首次给出了动态决定函数的详细公式,并提供了一种通过微流控系统测量合成元件(包括8个激活剂和5个抑制剂)所有参数的方法。构建了三个合成回路以表明DDM可以显著提高预测准确性,并可用于各种合成生物学应用。