Welkenhuysen Niek, Schnitzer Barbara, Österberg Linnea, Cvijovic Marija
Department of Mathematical Sciences, University of Gothenburg, Gothenburg, Sweden.
Department of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden.
Front Physiol. 2019 Jan 21;9:1964. doi: 10.3389/fphys.2018.01964. eCollection 2018.
Systems biology approaches provide means to study the interplay between biological processes leading to the mechanistic understanding of the properties of complex biological systems. Here, we developed a vector format rule-based Boolean logic model of the yeast cAMP-PKA, Snf1, and the Snf3-Rgt2 pathway to better understand the role of crosstalk on network robustness and function. We identified that phosphatases are the common unknown components of the network and that crosstalk from the cAMP-PKA pathway to other pathways plays a critical role in nutrient sensing events. The model was simulated with known crosstalk combinations and subsequent analysis led to the identification of characteristics and impact of pathway interconnections. Our results revealed that the interconnections between the Snf1 and Snf3-Rgt2 pathway led to increased robustness in these signaling pathways. Overall, our approach contributes to the understanding of the function and importance of crosstalk in nutrient signaling.
系统生物学方法提供了研究生物过程之间相互作用的手段,从而对复杂生物系统的特性进行机理理解。在此,我们开发了一种基于向量格式规则的酵母cAMP-PKA、Snf1和Snf3-Rgt2途径的布尔逻辑模型,以更好地理解串扰对网络稳健性和功能的作用。我们确定磷酸酶是该网络中常见的未知成分,并且从cAMP-PKA途径到其他途径的串扰在营养感知事件中起关键作用。该模型用已知的串扰组合进行模拟,随后的分析导致了对途径互连的特征和影响的识别。我们的结果表明,Snf1和Snf3-Rgt2途径之间的互连导致这些信号通路的稳健性增加。总体而言,我们的方法有助于理解串扰在营养信号传导中的功能和重要性。