User manual THE MATHWORKS SIMBIOLOGY 3

[. . . ] SimBiology® 3 User's Guide How to Contact MathWorks Web Newsgroup www. mathworks. com/contact_TS. html Technical Support www. mathworks. com comp. soft-sys. matlab suggest@mathworks. com bugs@mathworks. com doc@mathworks. com service@mathworks. com info@mathworks. com Product enhancement suggestions Bug reports Documentation error reports Order status, license renewals, passcodes Sales, pricing, and general information 508-647-7000 (Phone) 508-647-7001 (Fax) The MathWorks, Inc. 3 Apple Hill Drive Natick, MA 01760-2098 For contact information about worldwide offices, see the MathWorks Web site. SimBiology® User's Guide © COPYRIGHT 2005­2010 by The MathWorks, Inc. The software described in this document is furnished under a license agreement. The software may be used or copied only under the terms of the license agreement. [. . . ] specifies full dedimensionalization. · 'Full' For an example, see: "Command-Line Example -- Calculating Sensitivities" on page 3-37 Performing Sensitivity Analysis Using the Desktop You must have a model open in the desktop for this feature to be enabled. After opening a model, to get started with calculating sensitivities, do the following: 1 In the SimBiology desktop, from the Tasks menu select Add Model Task to model_name > Calculate sensitivities. 3-27 3 Analysis The desktop adds Sensitivity Analysis in the Project Explorer and opens the Sensitivity Analysis pane. 2 See the context-sensitive SimBiology Desktop Help for more information on how to set up sensitivity analysis. To access SimBiology Desktop Help, select Help > SimBiology Desktop Help. For an example, see: "Desktop Example -- Calculating Sensitivities" on page 3-29 References Ingalls, B. P, and Sauro, H. M. Sensitivity analysis of stoichiometric networks: an extension of metabolic control analysis to non-steady state trajectories. Martins, J. R. R. A. , Sturdza, P. , and Alanso, J. J. The connection between the complex-step derivative approximation and algorithmic differentiation. Martins, J. R. R. A. , Kroo, I. M. , and Alanso, J. J. An automated method for sensitivity analysis using complex variables. AIAA Paper 2000­0689. 3-28 Desktop Example -- Calculating Sensitivities Desktop Example -- Calculating Sensitivities In this section. . . "Overview" on page 3-29 "Prerequisites" on page 3-32 "Setting Options for Sensitivity Analysis" on page 3-33 "Getting Results for Sensitivity Analysis" on page 3-35 "References" on page 3-36 Overview This example shows you how to set up and calculate sensitivities in the SimBiology desktop. For information on how to calculate sensitivities at the command line, see "Command-Line Example -- Calculating Sensitivities" on page 3-37. About the Example Model This example uses the model from "Modeling a G Protein Cycle" in the SimBiology Model Reference documentation. This table shows the reactions used to model the G protein cycle and the corresponding rate parameters (rate constants) for each reaction. For reversible reactions, the forward rate parameter is listed first. Name 1 2 3 4 Receptor-ligand interaction Heterotrimeric G protein formation G protein activation Receptor synthesis and degradation Reaction L + R <-> RL Gd + Gbg -> G RL + G -> Ga + Gbg + RL Rate Parameters kRL, kRLm kG1 kGa kRdo, kRs R <-> null 3-29 3 Analysis No. Name 5 6 Receptor-ligand degradation G protein inactivation Reaction RL -> null Ga -> Gd Rate Parameters kRD1 kGd About This Example Yi et al. (2003) show that the rate of G protein inactivation is much lower in the mutant strain (kGd = 0. 004) relative to the wild-type strain (kGd = 0. 11), which explains the higher levels of activated G protein (Ga) over time as shown in the following figure. 3-30 Desktop Example -- Calculating Sensitivities Thus, the active G protein, Ga, is sensitive to the value of the parameter, kGd. Other species or parameters in the model can also affect levels of active G protein. To study the sensitivity of a species to other species or parameters in a model, you can perform sensitivity analysis. Sensitivity analysis lets you compute the time-dependent derivatives of one or more species (Output) relative to either model parameter values or species initial conditions (Input). First, it might be useful to explore the sensitivities of every species with respect to every parameter in the model. You can later narrow down the results to visualize the sensitivity results for Ga using plots. [. . . ] To edit a response, double-click the cells in the Value column to edit them. · Column Name -- Column header in the data set containing the observed response. · Component Name -- Component in the model representing the observed response. Tip After double-clicking a cell, press the down arrow key to display a list of possible values to choose from, select a name from the list, and then press Enter. 4-95 4 Pharmacokinetic Modeling To add a response, click and then click . . [. . . ]