Cell Cycle Complexity: Exploring the Structure of Persistent Subsystems in 414 Models

<b>Background</b>: The regulation of cellular proliferation and genomic integrity is controlled by complex surveillance mechanisms known as cell cycle checkpoints. Disruptions in these checkpoints can lead to developmental defects and tumorigenesis. <b>Methods</b>: To better understand these mechanisms, computational modeling has been employed, resulting in a dataset of 414 mathematical models in the BioModels database. These models vary significantly in detail and simulated processes, necessitating a robust analytical approach. <b>Results</b>: In this study, we apply the chemical organization theory (COT) to these models to gain insights into their dynamic behaviors. COT, which handles both ordinary and partial differential equations (ODEs and PDEs), is utilized to analyze the compartmentalized structures of these models. COT's framework allows for the examination of persistent subsystems within these models, even when detailed kinetic parameters are unavailable. By computing and analyzing the lattice of organizations, we can compare and rank models based on their structural features and dynamic behavior. <b>Conclusions</b>: Our application of the COT reveals that models with compartmentalized organizations exhibit distinctive structural features that facilitate the understanding of phenomena such as periodicity in the cell cycle. This approach provides valuable insights into the dynamics of cell cycle control mechanisms, refining existing models and potentially guiding future research in this area.