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. 2017 Feb 24;7:34. doi: 10.1038/s41598-017-00086-y

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© The Author(s) 2017

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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Analysis workflows for the cardiac signaling network. Step 1. Construct a large-scale cardiac signaling network; Step 2. Formulate the network as a mathematical model using the normalized equation modeling method; Step 3. Generate one million random parameter sets from standard uniform distributions; Step 4. Conduct the numerical simulation using ode15s function in MATLAB and verify the model by comparing the simulation results with experimental data; Step 5. Define apoptotic and hypertrophic phenotypes; Step 6. Calculate marginal distributions of parameters that are associated with apoptotic or hypertrophic phenotypes (plot A and plot B represent non-uniform marginal distributions and plot C represents a near-uniform marginal distribution; the lines colored in red denote a marginal distribution and dotted lines denote a uniform distribution); Step 7. Perform one distribution perturbation analyses; Step 8. Perform two distribution perturbation analyses; Step 9. Observe the change of phenotype distributions by distribution perturbation analyses.