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Crosstalk and Signalling Pathway Complexity - A Case Study on Synthetic Models

机译:串扰和信号通路的复杂性-以综合模型为例

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Crosstalk between signalling pathways have been intensively studied in wet laboratory experiments. More and more experimental evidences show that crosstalk is a very important component for maintaining biology systems robustness. In wet laboratory experiments, crosstalk are normally predicted by applying specific stimulus, i.e., various extracellular cues or individual gene suppressors or protein inhibitors. If significant difference between a control group without a specific stimulus and an experimental group with a specific stimulus is found, crosstalk is predicted. In terms of time complexity and cost, such experiments are commonly limited to small scales by using very few sampling time points. At the same time, few mathematical models have been proposed to analyse or predict crosstalk. This work investigates how crosstalk affects signalling pathway complexity and if such effect is significant for discrimination purpose, hence providing evidence for crosstalk prediction. Two crosstalk activities (positive and negative) based on simple synthetic transcription models are used for study. The study has found that crosstalk can change the steady-state gene expression order, hence making signalling pathway complex. The finding indicates that crosstalk is predictable using computer programs in top-down systems biology research.
机译:信号通路之间的串扰已在湿实验室实验中进行了深入研究。越来越多的实验证据表明,串扰是维持生物学系统鲁棒性的非常重要的组成部分。在湿实验室实验中,串扰通常是通过施加特定的刺激即各种细胞外提示或单个基因抑制剂或蛋白质抑制剂来预测的。如果发现没有特定刺激的对照组与具有特定刺激的实验组之间存在显着差异,则可以预测串扰。就时间复杂度和成本而言,此类实验通常通过使用很少的采样时间点而局限于小规模。同时,很少有人提出分析或预测串扰的数学模型。这项工作研究了串扰如何影响信号通路的复杂性,以及这种影响是否对区分目的很重要,从而为串扰预测提供了证据。基于简单的合成转录模型的两个串扰活动(正向和负向)用于研究。研究发现串扰可以改变稳态基因的表达顺序,从而使信号通路复杂化。该发现表明,在自上而下的系统生物学研究中,使用计算机程序可以预测串扰。

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