Team:Colombia Uniandes/Parameters

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Revision as of 19:40, 1 September 2013 (view source) D.olivera1320 (Talk | contribs) (→Nickel removal system) ← Older edit		Revision as of 19:49, 1 September 2013 (view source) D.olivera1320 (Talk | contribs) (→Nickel removal system) Newer edit →
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	A complete sensitivity analysis was performed in order to see which parameters have a significant importance in the model. Each parameter was evaluated in various orders of magnitude and the behaviour of the nickel intake was analysed.		A complete sensitivity analysis was performed in order to see which parameters have a significant importance in the model. Each parameter was evaluated in various orders of magnitude and the behaviour of the nickel intake was analysed.
-	Most of the parameters had a significant effect. Only the rate constant for the formation of the tetramer and the repressor destruction rate were the  parameters that compared with the others had little effect on the nickel intake:	+	Most of the parameters had a significant effect. Only the rate constant for the formation of the tetramer and the repressor destruction rate were the  parameters that compared with the others had little effect on the nickel intake. The first one needed to be found with the model, but after seeing that it has not a significant effect on the desired response an estimated order of magnitude is enough to run the deterministic model.
	[[File:repressordestructionses.png|left|950x800px]]		[[File:repressordestructionses.png|left|950x800px]]
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	[[File:basalprodrepanalysis.png|center|500x450px]]		[[File:basalprodrepanalysis.png|center|500x450px]]
		+	As said before most of the parameters showed to have influence in the model. The parameters related to the Hill's equation: The Maximum expression rate and the cooperation constant had the highest effect on the model and its value needs to be screened.
-		+	[[File:EffectNickel.png|left|950x800px]]
-		+
-		+
-	here were some parameters that had not a significant effect in the model which meant that the screening with these parameter was unnecessary. Some examples are shown below:	+

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Revision as of 19:49, 1 September 2013

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The second step in the deterministic model is to find the parameters that define the system. There are 3 possible ways to do this:

1. Literature: Many of the genes that we use in iGEM have been characterised before, and the constants that model their behaviour have been found. Sometimes an exact value is not found, so we have to find at least the order of magnitude or a range where the parameter can be found
2. Experiments: This is the most reliable way of knowing the parameters. But in our case we need the to perform de deterministic model first in order to see if the system works as expected in the lab. So the experimental way can only work to check if the parameters were correctly found.
3. Screening: If the parameters we are looking of are not found in literature we proceed to perform a screening of parameters as described in Colombia 2012 Team Wiki

Below is shown how we found the parameters for both of the projects:

Glucocorticoid sensor

After performing the literature research for the parameters the following values were found:

• The values for these parameter varied a lot depending on the glucocorticoid detected; as in the lab is planned to test the circuit with Dexamethasone all the parameters were done for this glucocorticoid.
• The values in red are the parameters that could not be found. An estimated order of magnitude was assessed supported in the literature read.
• As the part of the chimera that is going to activate transcription is Gal4p the values for the activation of the gene are assumed to be the same as the pure protein.
• Some of the destruction rates are not found so it is assumed the concentration of the protein is significantly reduced only when the cell divides

Sensitivity Analysis

In order to see which if the parameters had a significant effect in the signal response, we performed a Sensitivity analysis. For each parameter, we took the value found in the literature (or guessed value) and evaluated the model in a range that varied from one order of magnitude below to one order of magnitude greater. Depending on how much the response varied to each parameter the screening was planned.

After perfoming the analysis we found some parameters that had little effect on the desired response of the system. For example the destruction rate of Glucocorticoid inside the cell and the reverse kinetic constant for the formation of the complex:

The parameters related to the hill expression had a significant effect on the desired response, for this reason and given the fact that two of the three parameters had an estimated order of magnitud the screening of parameters was focused on this part of the model.

You can see the complete Sensitivity Analysis here.

Nickel removal system

After a research for parameters in the literature research was done the following values were found:

• The values in red are the parameters that could not be found. An estimated order of magnitude was assessed supported in the literature read.
• Some of the destruction rates are not found so it is assumed the concentration of the protein is significantly reduced only when the cell divides

Sensitivity Analysis

A complete sensitivity analysis was performed in order to see which parameters have a significant importance in the model. Each parameter was evaluated in various orders of magnitude and the behaviour of the nickel intake was analysed.

Most of the parameters had a significant effect. Only the rate constant for the formation of the tetramer and the repressor destruction rate were the parameters that compared with the others had little effect on the nickel intake. The first one needed to be found with the model, but after seeing that it has not a significant effect on the desired response an estimated order of magnitude is enough to run the deterministic model.

The repressor basal production rate is one of the parameters that needs to be found with the model. As can be seen below this parameter has a strong influence on the response of the system in a small range (0.8-1.3) . After 1.4 the response of the system is not influenced by the change of the basal production. The parameter can be picked after 1.4 because it has no significant influence in the response and the intake of nickel is high enough.

As said before most of the parameters showed to have influence in the model. The parameters related to the Hill's equation: The Maximum expression rate and the cooperation constant had the highest effect on the model and its value needs to be screened.

Here is the complete document with the results for all the parameters