Laboratory of Engineering Sciences, Computer Sciences and Imaging, UMR 7357 (University of Strasbourg / CNRS), Illkirch, France.
PLoS One. 2021 Mar 30;16(3):e0249234. doi: 10.1371/journal.pone.0249234. eCollection 2021.
Gene regulatory networks exhibiting Boolean behaviour, e.g. AND, OR or XOR, have been routinely designed for years. However, achieving more sophisticated functions, such as control or computation, usually requires sequential circuits or so-called state machines. For such a circuit, outputs depend both on inputs and the current state of the system. Although it is still possible to design such circuits by analogy with digital electronics, some particularities of biology make the task trickier. The impact of two of them, namely the stochasticity of biological processes and the inhomogeneity in the response of regulation mechanisms, are assessed in this paper. Numerical simulations performed in two use cases point out high risks of malfunctions even for designed GRNs functional from a theoretical point of view. Several solutions to improve reliability of such systems are also discussed.
多年来，人们已经习惯设计表现出布尔行为（如 AND、OR 或 XOR）的基因调控网络。然而，要实现更复杂的功能，如控制或计算，通常需要使用顺序电路或所谓的状态机。对于这样的电路，输出不仅取决于输入，还取决于系统的当前状态。尽管仍然可以通过类比数字电子学来设计这样的电路，但生物学的一些特殊性使得这项任务更加棘手。本文评估了其中两个特性的影响，即生物过程的随机性和调节机制响应的不均匀性。在两个用例中进行的数值模拟指出，即使从理论角度来看设计的 GRN 是功能正常的，也存在很高的故障风险。还讨论了几种提高此类系统可靠性的解决方案。
