Boolean models represent a drastic simplification of complex biomolecular systems, and yet accurately predict system properties, e.g., effective control strategies. Why is this? Parameter robustness has been highlighted as a general feature of biomolecular systems and may play an important role in the accuracy of Boolean models. We argue here that a useful way to view a system’s controllability properties is through its repertoire of self-sustaining positive circuits (stable motifs). We examine attractor control and self-sustaining circuits within the cell cycle restriction switch, a bistable regulatory circuit that allows or prevents entry into the cell cycle. We explore this system using three models: a previously published Boolean model, a Hill kinetics model that we construct from the Boolean model using the HillCube methodology, and a reaction-based model we construct from the literature. We highlight the robustness of stable motifs across these three levels of modeling detail. We also show how consideration of control-robust regulatory circuits can aid in parameter specification.

中文翻译：

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跨信息梯度控制细胞周期限制开关

布尔模型代表了复杂的生物分子系统的极大简化，并且准确地预测了系统特性，例如有效的控制策略。为什么是这样？参数稳健性已被强调为生物分子系统的一般特征，并且可能在布尔模型的准确性中发挥重要作用。我们在这里争辩说，查看系统可控性属性的一种有用方法是通过其自我维持的正电路（稳定基序）的全部内容。我们检查了细胞周期限制开关内的吸引子控制和自我维持电路，这是一种允许或阻止进入细胞周期的双稳态调节电路。我们使用三个模型来探索这个系统：之前发布的布尔模型，我们使用 HillCube 方法从布尔模型构建的希尔动力学模型，以及我们从文献中构建的基于反应的模型。我们强调了在这三个建模细节层次上稳定基序的稳健性。我们还展示了对控制鲁棒性调节电路的考虑如何有助于参数规范。