Abstract
In this Chapter you will learn how to carry out, with COPASI, some of the analysis techniques described in Chap. 10. Initially, we will use a new model for the Toggle Switch, which takes into account promoter leakage, to run sensitivity analysis and show that the circuit is not robust against variations in the value of the leakage translation rate constant. We will then use the same model to see how to run a circuit optimization with a stochastic algorithm (Simulated Annealing). This procedure is used to find new values for some selected kinetic parameters such that the circuit performance is improved. As in every optimization problem, you will have to specify a proper objective function. Finally, on a simpler circuit, where a reporter protein is expressed in the presence of an inducer chemical, you will see how to fit a model to two different data sets in order to estimate the Hill constant and coefficient.
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Notes
- 1.
This is a local sensitivity analysis around the parameter values in Table 11.1.
- 2.
An increase in λ 1 causes a decrease in the concentration of \(p_1^a\), which implies a lower number of molecules of R 2 at steady state. Hence, at the equilibrium the system has a higher concentration of \(p_2^a\), the species that leads the production of R 1.
- 3.
Due to the circuit scheme and the parameter values in Table 11.1, analogous considerations hold for R 2.
- 4.
See Chap. 3 for general instructions about both the “Parameter Scan” task and the creation of a “Report”.
- 5.
The symbol × indicates the Cartesian product.
- 6.
You can associate each optimization with a report. Click on “Report” in the “Optimization” definition panel, select “Optimization” as “Report definition”, set the “Target” file that will contain the report, and then click on “OK”.
- 7.
If you defined it as a “Global Quantity”, you will find it under “Global Quantities”, “Initial Values”.
- 8.
Both for K H and n use as “Start Value” the value of the “Lower Bound”.
- 9.
- 10.
Click on “i2.txt”. “Copy Settings” is set, by default, to “from previous”, which is fine with our simulations.
- 11.
The data files were indeed generated with these values and then modified by hands.
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Marchisio, M.A. (2018). Circuit Analysis with COPASI. In: Introduction to Synthetic Biology. Learning Materials in Biosciences. Springer, Singapore. https://doi.org/10.1007/978-981-10-8752-3_11
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DOI: https://doi.org/10.1007/978-981-10-8752-3_11
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