TY - JOUR
T1 - CONTROLLING the CELL CYCLE RESTRICTION SWITCH ACROSS the INFORMATION GRADIENT
AU - Rozum, Jordan C.
AU - Albert, Réka
N1 - Funding Information:
This work was supported by grants NSF PHY 1205840 and NSF PHY 1545832 to RA. We thank Dávid Deritei for helpful discussions regarding the BRS model upon which much of this work is built.
Publisher Copyright:
© 2019 World Scientific Publishing Company.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - 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.
AB - 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.
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U2 - 10.1142/S0219525919500206
DO - 10.1142/S0219525919500206
M3 - Article
AN - SCOPUS:85081556879
SN - 0219-5259
VL - 22
JO - Advances in Complex Systems
JF - Advances in Complex Systems
IS - 7-8
M1 - 1950020
ER -