INESC-ID/IST, Rua Alves Redol 9, Lisboa 1000-029, Portugal.
IET Syst Biol. 2011 Sep;5(5):308-16. doi: 10.1049/iet-syb.2011.0001.
Qualitative models allow understanding the relation between the structure and the dynamics of gene regulatory networks. The dynamical properties of these models can be automatically analysed by means of formal verification methods, like model checking. This facilitates the model-validation process and the test of new hypotheses to reconcile model predictions with the experimental data.
The authors report in this study the qualitative modelling and simulation of the transcriptional regulatory network controlling the response of the model eukaryote Saccharomyces cerevisiae to the agricultural fungicide mancozeb. The model allowed the analysis of the regulation level and activity of the components of the gene mancozeb-induced network controlling the transcriptional activation of the FLR1 gene, which is proposed to confer multidrug resistance through its putative role as a drug eflux pump. Formal verification analysis of the network allowed us to confront model predictions with the experimental data and to assess the model robustness to parameter ordering and gene deletion.
This analysis enabled us to better understand the mechanisms regulating the FLR1 gene mancozeb response and confirmed the need of a new transcription factor for the full transcriptional activation of YAP1. The result is a computable model of the FLR1 gene response to mancozeb, permitting a quick and cost-effective test of hypotheses prior to experimental validation.
定性模型可以帮助理解基因调控网络的结构和动态之间的关系。这些模型的动态特性可以通过形式验证方法（如模型检查）自动分析。这有助于模型验证过程和新假设的测试，以协调模型预测与实验数据。
本研究报告了对控制模型真核生物酿酒酵母对农业杀真菌剂代森锰锌响应的转录调控网络的定性建模和模拟。该模型允许分析控制 FLR1 基因转录激活的基因曼克泽布诱导网络的调控水平和活性，该基因被认为通过其作为药物外排泵的潜在作用赋予多药耐药性。对网络的形式验证分析使我们能够将模型预测与实验数据进行对比，并评估模型对参数排序和基因缺失的鲁棒性。
这项分析使我们能够更好地理解调节 FLR1 基因曼克泽布反应的机制，并证实了需要一个新的转录因子来实现 YAP1 的完全转录激活。结果是对曼克泽布诱导的 FLR1 基因反应的可计算模型，允许在实验验证之前快速、经济高效地测试假设。
