Traynard Pauline, Fauré Adrien, Fages François, Thieffry Denis
Computational Systems Biology Team, Institut de Biologie de L'Ecole Normale Supérieure (IBENS), CNRS, Inserm, Ecole Normale Supérieure, PSL Research University, Paris, France EPI Lifeware, Inria Inria Saclay Ile-de-France, Palaiseau, France.
Graduate School of Science and Engineering, Yamaguchi University, Yamaguchi, Japan.
Bioinformatics. 2016 Sep 1;32(17):i772-i780. doi: 10.1093/bioinformatics/btw457.
Understanding the temporal behaviour of biological regulatory networks requires the integration of molecular information into a formal model. However, the analysis of model dynamics faces a combinatorial explosion as the number of regulatory components and interactions increases.
We use model-checking techniques to verify sophisticated dynamical properties resulting from the model regulatory structure in the absence of kinetic assumption. We demonstrate the power of this approach by analysing a logical model of the molecular network controlling mammalian cell cycle. This approach enables a systematic analysis of model properties, the delineation of model limitations, and the assessment of various refinements and extensions based on recent experimental observations. The resulting logical model accounts for the main irreversible transitions between cell cycle phases, the sequential activation of cyclins, and the inhibitory role of Skp2, and further emphasizes the multifunctional role for the cell cycle inhibitor Rb.
The original and revised mammalian cell cycle models are available in the model repository associated with the public modelling software GINsim (http://ginsim.org/node/189).
Supplementary data are available at Bioinformatics online.
理解生物调控网络的时间行为需要将分子信息整合到一个形式化模型中。然而，随着调控组件和相互作用数量的增加，模型动力学分析面临组合爆炸问题。
我们使用模型检查技术在没有动力学假设的情况下验证由模型调控结构产生的复杂动力学性质。通过分析控制哺乳动物细胞周期的分子网络的逻辑模型，我们展示了这种方法的强大功能。这种方法能够对模型性质进行系统分析，划定模型局限性，并根据最近的实验观察评估各种改进和扩展。所得的逻辑模型解释了细胞周期各阶段之间主要的不可逆转变、细胞周期蛋白的顺序激活以及Skp2的抑制作用，并进一步强调了细胞周期抑制剂Rb的多功能作用。
原始和修订后的哺乳动物细胞周期模型可在与公共建模软件GINsim相关联的模型库中获取（http://ginsim.org/node/189）。
补充数据可在《生物信息学》在线获取。
