Towards abstraction of computational modelling of mammalian cell cycle: Model reduction pipeline incorporating multi-level hybrid petri nets.

Journal of Theoretical Biology
Ali AbroudiDon Kulasiri

Abstract

Cell cycle is a large biochemical network and it is crucial to simplify it to gain a clearer understanding and insights into the cell cycle. This is also true for other biochemical networks. In this study, we present a model abstraction scheme/pipeline to create a minimal abstract model of the whole mammalian cell cycle system from a large Ordinary Differential Equation model of cell cycle we published previously (Abroudi et al., 2017). The abstract model is developed in a way that it captures the main characteristics (dynamics of key controllers), responses (G1-S and G2-M transitions and DNA damage) and the signalling subsystems (Growth Factor, G1-S and G2-M checkpoints, and DNA damage) of the original model (benchmark). Further, our model exploits: (i) separation of time scales (slow and fast reactions), (ii) separation of levels of complexity (high-level and low-level interactions), (iii) cell-cycle stages (temporality), (iv) functional subsystems (as mentioned above), and (v) represents the whole cell cycle - within a Multi-Level Hybrid Petri Net (MLHPN) framework. Although hybrid Petri Nets is not new, the abstraction of interactions and timing we introduced here is new to cell cycle and Petri Nets. Importantly, our models...Continue Reading

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