Modeling Formalisms in Systems Biology of Apoptosis
Apoptosis is a form of cellular suicide central to various aspects in biology including tissue homeostasis, embryonic development, carcinogenesis, and neurodegenerative disorders. Quantitative modeling approaches provided valuable insights into the digital and irreversible nature of apoptosis initiation. In this chapter, we summarize the mathematical formalisms used in systems biology of apoptosis. In addition, we give an overview of apoptosis-related research questions that can be addressed by modeling. Moreover, we review top-down and bottom-up modeling approaches applied to apoptosis, and particularly focus on ordinary differential equation (ODE) modeling. Basic concepts such as bistability and sensitivity analysis are introduced, and a review of apoptosis-related ODE models is provided. We describe bistability, temporal switching, crosstalk between death and survival, and also discuss approaches to model cell-to-cell variability.
KeywordsMitochondrial Outer Membrane Permeabilization Ordinary Differential Equation Model Unstable Steady State Extrinsic Noise Apoptosis Initiation
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