Modeling CD4+ T cell differentiation using COPASI and Cell Designer

The following is a Cell Designer-based illustration of the intracellular network model of CD4+ T cell differentiation that reproduces four functional subsets: T helper (Th)1, Th2, Th17 and regulatory T cells. The model is available for download in CellDesigner xml format (right click the link or ctrl+left click for Mac machines to save the model source file). We have tested that the model is compatible with Cell Designer 4.1.

This model has been lastly updated on Jan 14th, 2012. Here is the release note: Cytokine externalization is a key process in CD4+ T cell differentiation because of its paracrine and autocrine effect. The CD4+ differentiation model was before set up with cytokines produced as final products in the mathematical model. With this new update, cytokines are being both internalized and externalized. Thus, a cytokine produced can affect differentiation by being externalized and then act as an inductor. This refinement will allow more complex differentiation studies. Also, activated transcription factors are now highlighted with a discontinued contour to be more easily detectable. Moreover, their shapes have been rearranged so now the transcription factors have a squared shape and the cytokines an oval one.

For previously versions, please go to the archive page.

The primary MIEP Team member responsible for maintaining this model is Adria Carbo at the Virginia Bioinformatics Institute. Please contact him with any questions or comments.

(Click on the image for a user-friendly interactive CellPublisher model.)

Cell Designer image: COPASI model of CD4+ T cell differentiation

Statistical Analysis
Fitted specie1 No. of Experimental Set Experimental induced phenotype Objective value2 Root Mean Square Error Mean Error Mean St. Deviation
IL23R #1 iTreg 0.02 0.08165 -3.70e-17 0.08165
FOXP3 #2 iTreg 1.26e-16 1.12e-8 1.12e-8
IL17_ratio #4 Th17 142.396 5.9664 -2.9842 5.16655
IL17 #3 Th17 0.06201 0.24902 0.24902
INFg #3 Th17 8.80e-7 9.380e-4 -9.380e-4
FOXP3_ratio #4 Th17 1.25e-6 5.5e-4 4.194e-4 3.701e-4
IL4 #5 Th2 1.53255 0.505396 0.29067 0.413444
INFg #6 Th2 7.41e-17 8.61e-9 -8.61e-9
IL2 #7 Th1 1.1471e-7 2.395e-4 -1.798e-4 1.582e-4
INFg #7 Th1 3.572 0.40294 0.37702 0.14219
  1. A fitted specie is fitted computationally using experimental data and simulation algorithms
  2. The objective value is the value that COPASI targets based on the experimental data and the computational simulation



 

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