Structural Robustness of Biochemical Networks: Quantifying Robustness and Identifying Fragilities
Structural Robustness of Biochemical Networks: Quantifying Robustness and Identifying Fragilities
This chapter covers the explicit perturbations of the network structure. It addresses the models of the mitogen-activated protein kinase (MAPK) signaling cascade, metabolic oscillations in white blood cells, and the mammalian circadian clock. It shows that the Goodwin oscillator clears the biological interpretation of applied perturbations and their impact on the network function. It notes that small structural perturbations can induce bistability and sustained oscillations in the signaling for the MAPK model. For the neutrophil model, a specific metabolic reaction is determined as a severe fragility and a small delay in this reaction is shown to remove the oscillatory behavior. For the relatively robust circadian clock model, structural robustness analysis identifies a 5-state subnetwork within the full 16-state network chiefly responsible for the circadian oscillations.
Keywords: network structure, mitogen-activated protein kinase, metabolic oscillations, white blood cells, mammalian circadian clock, Goodwin oscillator, structural robustness, oscillations, signaling cascade, structural perturbations
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