Guespin-Michel Janine F, Bernot Gilles, Comet Jean Paul, Mérieau Annabelle, Richard Adrien, Hulen Christian, Polack Benoit
Laboratoire de microbiologie du froid, EA 2123, Université de Rouen, F-76 821 Mt St Aignan, France.
Acta Biotheor. 2004;52(4):379-90. doi: 10.1023/B:ACBI.0000046604.18092.a7.
Mucoidy and cytotoxicity arise from two independent modifications of the phenotype of the bacterium Pseudomonas aeruginosa that contribute to the mortality and morbidity of cystic fibrosis. We show that, even though the transcriptional regulatory networks controlling both processes are quite different from a molecular or mechanistic point of view, they may be identical from a dynamic point of view: epigenesis may in both cases be the cause of the acquisition of these new phenotypes. This was highlighted by the identity of formal graphs modelling these networks. A mathematical framework based on formal methods from computer science was defined and implemented with a software environment. It allows an easy and rigorous validation and certification of these models and of the experimental methods that can be proposed to falsify or validate the underlying hypothesis.
黏液样变性和细胞毒性源于铜绿假单胞菌表型的两种独立改变，这两种改变会导致囊性纤维化的死亡率和发病率上升。我们发现，尽管从分子或机制角度来看，控制这两个过程的转录调控网络有很大不同，但从动态角度来看它们可能是相同的：在这两种情况下，表观遗传可能都是这些新表型获得的原因。对这些网络进行建模的形式图的一致性突出了这一点。我们定义了一个基于计算机科学形式方法的数学框架，并在一个软件环境中实现。它允许对这些模型以及为证伪或验证潜在假设而提出的实验方法进行轻松且严格的验证和认证。
