Center for Biological Engineering, Biomolecular Science and Engineering Program, Department of Mechanical Engineering, Center for Control, Dynamical Systems, and Computation, University of California, Santa Barbara, CA, USA.
Department of Life Sciences, POSTECH, Pohang, South Korea.
J R Soc Interface. 2021 Sep;18(182):20210413. doi: 10.1098/rsif.2021.0413. Epub 2021 Sep 8.
Synthetic gene networks are frequently conceptualized and visualized as static graphs. This view of biological programming stands in stark contrast to the transient nature of biomolecular interaction, which is frequently enacted by labile molecules that are often unmeasured. Thus, the network topology and dynamics of synthetic gene networks can be difficult to verify or , due to the presence of unmeasured biological states. Here we introduce the dynamical structure function as a new mesoscopic, data-driven class of models to describe gene networks with incomplete measurements of state dynamics. We develop a network reconstruction algorithm and a code base for reconstructing the dynamical structure function from data, to enable discovery and visualization of graphical relationships in a genetic circuit diagram as rather than static, unknown weights. We prove a theorem, showing that dynamical structure functions can provide a data-driven estimate of the size of crosstalk fluctuations from an idealized model. We illustrate this idea with numerical examples. Finally, we show how data-driven estimation of dynamical structure functions can explain failure modes in two experimentally implemented genetic circuits, a previously reported genetic circuit and a new -based transcriptional event detector.
合成基因网络通常被概念化为和可视化作为静态图。这种生物编程的观点与生物分子相互作用的瞬态性质形成鲜明对比，生物分子相互作用通常由不稳定的分子来执行，而这些分子往往是无法测量的。因此，由于存在未测量的生物状态，合成基因网络的网络拓扑和动态特性可能难以验证或推断。在这里，我们引入动态结构函数作为一种新的介观、数据驱动的模型类别，用于描述状态动态测量不完全的基因网络。我们开发了一种网络重构算法和一个代码库，用于从数据中重构动态结构函数，以能够在遗传电路图中发现和可视化图形关系，而不是静态的、未知的权重。我们证明了一个定理，表明动态结构函数可以从理想模型提供对串扰波动大小的一种数据驱动的估计。我们用数值例子来说明这个想法。最后，我们展示了如何通过对动态结构函数的数据驱动估计来解释两个实验实现的遗传电路中的故障模式，一个是以前报道过的遗传电路，另一个是基于的转录事件探测器。
