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Evaluation of Design Strategies for Time Course Experiments in Genetic Networks: Case Study of the XlnR Regulon in Aspergillus niger

机译:遗传网络中的时程实验设计策略的评估:黑曲霉中的XlnR调节子的案例研究

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One of the challenges in genetic network reconstruction is finding experimental designs that maximize the information content in a data set. In this paper, the information value of mRNA transcription time course experiments was used to compare experimental designs. The study concerns the dynamic response of genes in the XlnR regulon of Aspergillus niger, with the goal to find the best moment in time to administer an extra pulse of inducing D-xylose. Low and high D-xylose pulses were used to perturb the XlnR regulon. Evaluation of the experimental methods was based on simulation of the regulon. Models that govern the regulation of the target genes in this regulon were used for the simulations. Parameter sensitivity analysis, the Fisher Information Matrix (FIM) and the modified E-criterion were used to assess the design performances. The results show that the best time to give a second D-xylose pulse is when the D-xylose concentration from the first pulse has not yet completely faded away. Due to the presence of a repression effect the strength of the second pulse must be optimized, rather than maximized. The results suggest that the modified E-criterion is a better metric than the sum of integrals of absolute sensitivity for comparing alternative designs.
机译:遗传网络重建中的挑战之一是寻找能够最大化数据集中信息内容的实验设计。本文利用mRNA转录时程实验的信息价值对实验设计进行了比较。这项研究涉及黑曲霉XlnR调控区中基因的动态响应,目的是及时发现最佳时机以额外诱导D-木糖。低和高D-木糖脉冲被用来扰动XlnR调节子。实验方法的评估是基于规则调节器的仿真。用于控制该调节子中靶基因调控的模型用于模拟。使用参数敏感度分析,Fisher信息矩阵(FIM)和修改后的E标准来评估设计性能。结果表明,发出第二个D-木糖脉冲的最佳时间是来自第一个脉冲的D-木糖浓度尚未完全消失。由于存在抑制效应,因此必须优化而不是最大化第二脉冲的强度。结果表明,与比较其他设计的绝对灵敏度积分之和相比,修改后的E标准是一种更好的指标。

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