Academy of Integrated Science

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Mathematical Models of Death Signaling Networks
Srinivasan, Madhumita; Clarke, Robert; Kraikivski, Pavel (MDPI, 2022-10-01)
This review provides an overview of the progress made by computational and systems biologists in characterizing different cell death regulatory mechanisms that constitute the cell death network. We define the cell death network as a comprehensive decision-making mechanism that controls multiple death execution molecular circuits. This network involves multiple feedback and feed-forward loops and crosstalk among different cell death-regulating pathways. While substantial progress has been made in characterizing individual cell death execution pathways, the cell death decision network is poorly defined and understood. Certainly, understanding the dynamic behavior of such complex regulatory mechanisms can be only achieved by applying mathematical modeling and system-oriented approaches. Here, we provide an overview of mathematical models that have been developed to characterize different cell death mechanisms and intend to identify future research directions in this field.