Corbat2021 - Apoptotic Reaction Model.models

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Apoptotic Reaction Model is an ordinary differential equation model describing every species in the apoptotic cascade and trained to simulate experiments with extrinsic or intrinsic stimuli. It is based on the model introduced by Albeck et al. 2008 and contains a missing feedback between effector caspase 3 and intrinsic caspase 9 to be able to predict results from experiments with either extrinsic and intrinsic stimuli.
Related Publication
  • An Integrative Apoptotic Reaction Model for extrinsic and intrinsic stimuli
  • Agustin, Mauro Silberberg, Hern\'an Edgardo Grecco
  • biorXiv , 5/ 2021 , DOI: 10.1101/2021.05.21.444824
  • Department of Physics, FCEN, University of Buenos Aires and IFIBA, CONICET, Buenos Aires, Argentina
  • Apoptosis, a form of programmed cell death central to all multicellular organisms, plays a key role during organism development and is often misregulated in cancer. Devising a single model applicable to distinct stimuli and conditions has been limited by lack of robust observables. Indeed, previous numerical models have been tailored to fit experimental datasets in restricted scenarios, failing to predict response to different stimuli. We quantified the activity of three caspases simultaneously upon intrinsic or extrinsic stimulation to assemble a comprehensive dataset. We measured and modeled the time between maximum activity of intrinsic, extrinsic and effector caspases, a robust observable of network dynamics, to create the first integrated Apoptotic Reaction Model (ARM). Observing how effector caspases reach maximum activity first irrespective of stimuli used, led us to identify and incorporate a missing feedback into a successful model for extrinsic stimulation. By simulating different recently performed experiments, we corroborated that ARM adequately describes them. This integrated model provides further insight into the indispensable feedback from effector caspase to initiator caspases.

Metadata information

Mathematical Modelling Ontology Ordinary differential equation model

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Model files

arm.sbml SBML Model 72.06 KB Preview | Download

  • Model originally submitted by : Agustin
  • Submitted: 22-May-2021 15:23:09
  • Last Modified: 22-May-2021 15:23:09
  • Version: 2 public model Download this version
    • Submitted on: 22-May-2021 15:23:09
    • Submitted by: Agustin
    • With comment: Updated model publication to biorXiv
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