Optimization examples

Here we give some examples of the BioUML usage for solving the problem of parameter estimation applied to the models of biochemical pathways. For details about creation your oun optimization document in BioUML, see the chapter Optimization document. Some information about the optimization methods implemented in BioUML is done in the chapter Optimization problem.

Testing the convergence rate of the optimization methods

• Optimization document: data > Examples > Optimization > Data > Documents > test_case_1A
• Model: data > Examples > Optimization > Data > Diagrams > diagram_1A
• Experimental data: data > Examples > Optimization > Data > Experiments > exp_data_1

To analyze a convergence rate of the optimization methods implemented in BioUML, we considered a reaction chain extracted from the model by Neumann et al. [1] and representing activation of caspase-8 triggered by the receptor CD95 (APO-1/Fas).

The test model of caspase-8 activation

ID Reactions Reaction rates r1 CD95L + FADD:CD95R → DISC k1 ⋅ [CD95L] ⋅ [CD95R:FADD] r2 DISC + pro8 → DISC:pro8 k2 ⋅ [DISC] ⋅ [pro8] r3 DISC:pro8 + pro8 → 2 · p43/p41 k3 ⋅ [DISC:pro8] ⋅ [pro8] r4 2 · p43/p41 → casp8 k4 ⋅ [p43/p41]2 r5 casp8 → k5 ⋅ [casp8]

We performed estimation of parameters using the search space defined as:

0 ≤ k₁ ≤ 1, 0 ≤ k₅ ≤ 0.1, 0 ≤ k_i ≤ 10⁻³, i = 2, 3, 4.

References

1. Neumann L., Pforr C., Beaudouin J., Pappa A., Fricker N., Krammer P.H., Lavrik I.N., Eils R. Dynamics within the CD95 death-inducing signaling complex decide life and death of cells. Molecular Systems Biology. 2010. 6:352.