Team:OUC-China/Modeling/NoiseAnalysis

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<h1>Noise analysis-model</h1>
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<h1 style="border:none;">Noise analysis-model</h1>
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<p><strong>Aim:</strong><span></span>To analysis the noise in the ternary system .
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<p><strong>Aim:</strong><span></span>To figure out whether output is robust when presented with intrinsic noise.
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<br/><span></span>1. Use the Gillespie algorithm to perform the stochastic analysis;
<br/><span></span>1. Use the Gillespie algorithm to perform the stochastic analysis;
<br/><span></span>2. Draw probability distribution figures (pdf);
<br/><span></span>2. Draw probability distribution figures (pdf);
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<br/><span></span>3. Computing the noise statistically.
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<br/><span></span>3. Compute the noise statistically.
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We refer to the most classical Gillespie algorithm and lots of improvements have been made by later generation. For example, Sagar Indurkhya et al mentioned that Dynamic Monte Carlo methods are a common means of simulating the time-evolution of chemical systems.The Gillespie Algorithm (SSA) [1] is the standard algorithm for this process, and has inspired a variety of derivative methods that speed up computation, including the Optimized Direct Method (ODM) [2] and the Next Reaction Method (NRM) [3]. These methods, however, are still computationally costly.Now,we still use the classical algorithm.:
We refer to the most classical Gillespie algorithm and lots of improvements have been made by later generation. For example, Sagar Indurkhya et al mentioned that Dynamic Monte Carlo methods are a common means of simulating the time-evolution of chemical systems.The Gillespie Algorithm (SSA) [1] is the standard algorithm for this process, and has inspired a variety of derivative methods that speed up computation, including the Optimized Direct Method (ODM) [2] and the Next Reaction Method (NRM) [3]. These methods, however, are still computationally costly.Now,we still use the classical algorithm.:
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<p>ηij is use to describe the noise, where：
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<p>ηij is used to describe the noise, where：
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<p><span></span>The value of noise is ηi2 .
<p><span></span>The value of noise is ηi2 .
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If the mean([m]1:1)-mean([m]1:2) > 5 times the noise, we identify the output wouldn’t be drown in noise.
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If the mean([m]1:1)-mean([m]1:2) >> the value of noise, we identify the output wouldn’t be drown in noise.
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<h2>Ratio sensor</h2>
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<h2>Result_Ratio sensor</h2>
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<p><span></span>To get how the system behaves in the stochastic regime, we plotted the mRNA and sRNA molecule numbers as function of time(at left). Then we obtain the histogram(at right) The histogram make clear that the mean is around the mean, thus we can conclude that the system is stable.  Since the numbers of mRNA molecules do not jump between two or more distinct values we can assume that the system is not bistable or multistable.
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<p style="text-align:center; font-size:90%;">Figure 1: the parameters which is from the parameter sweep are used in the Gillespie algorithm  the left are the sRNA and mRNA change with time goes by. The right are the mRNA of probability distribution frequency (pdf)
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<p style="text-align:center; font-size:90%;">Fig.1 Pdf means probability distribution frequency  
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<p>The respective mean value and variance are shown as follows:
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<p>The statistics is given below:
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<br/><br/><p style="text-align:center; font-size:90%;">Table 1:using the Gillespie algorithm, we get the mean and variance when as1:as2 equal to 0.5,1,2.</p>
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<p>then we caculate the noise :
 
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<br/><br/><p style="text-align:center; font-size:90%;">Table 2: From the table, We can conclude that the noise is very small and it’s nearly the same when as1:as2 equal 0.5 and as1:as2 equal 2 .it’s fit the ode equations.<br/>
 
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<p><span></span>From the table2 , we can conclude that the noise almost the same. And the mean of mRNA>>difference value between as1:as2=1 .At the same time, the mean of mRNA>>difference value between as1:as2=1 and 2. So when as1:as2 is equal to 1:1,the equilibrium concentration isn’t drown the noise.
 
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<h2>Comparator</h2>
<h2>Comparator</h2>
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<p><span></span>We have done the same thing in the comparator. The differences are the km and ks , which values are from the parameter sweep.
 
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<br/><p style="text-align:center; font-size:90%;">Fig.2 Pdf stands for probability distribution frequency.</p>
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<a><img src="https://static.igem.org/mediawiki/2012/1/18/Ouc-modeling-math22.jpg"></a>
 
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<a><img style="margin-left:380px; margin-top: -290px;" src="https://static.igem.org/mediawiki/2012/b/b2/Ouc-modeling-math31.jpg"></a>
 
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<a><img src="https://static.igem.org/mediawiki/2012/1/15/Ouc-modeling-math32.jpg"></a>
 
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<a><img style="margin-left:380px; margin-top: -290px;" src="https://static.igem.org/mediawiki/2012/b/bc/Ouc-modeling-math25.jpg"></a>
 
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<a><img src="https://static.igem.org/mediawiki/2012/e/e2/Ouc-modeling-math34.jpg"></a>
 
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<a><img style="margin-left:380px; margin-top: -290px;" src="https://static.igem.org/mediawiki/2012/9/9b/Ouc-modeling-math35.jpg"></a>
 
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<br/><p style="text-align:center; font-size:90%;">Figure 2: the same principle is used the comparator. the left are the sRNA and mRNA change with time goes by. The right are the mRNA of probability distribution frequency (pdf)</p>
 
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<p>The statistics is given below:
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<p>then we compute the noise :
 
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<a><img src="https://static.igem.org/mediawiki/2012/c/c4/Ouc-c_analysis2.png"></a>
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<a><img style="margin-left:65px;" src="https://static.igem.org/mediawiki/2012/5/58/Ouc-modeling-math36.jpg"></a>
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<br/><br/><p style="text-align:center; font-size:90%;">Table 3:Using the Gillespie algorithm, we get the mean and variance values when as1:as2 equal to 0.5,1</p><br/>
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<a><img style="margin-left:65px;" src="https://static.igem.org/mediawiki/2012/7/7f/Ouc-modeling-math37.jpg"></a>
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<br/><br/><p style="text-align:center; font-size:90%;">Table 4: From the table, We can conclude that the noise is also very small .<br/>
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<br/><br/><p><span></span>Then we calculate the noise value
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From the table 4 ,we can observe that the mean of mRNA>>difference value between as1:as2=1 and 0.5.At the same time, the mean of mRNA>>difference value between as1:as2=1 and 2. So when as1:as2 is equal to 1:1,the equilibrium concentration isn’t drown the noise.
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<h2>Conclusion</h2>
<h2>Conclusion</h2>
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<p><span></span> By using the noise analysis, we can conclude that the mRNA isn’t drawn the noise,. that’s  by simulating the real organism, our model also meets the requirements to design the experiment.
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<p><span></span>Both ratio sensor and comparator, the change of mRNA concentration is robust enough when presented with noise(mean([m]1:1)-mean([m]1:2) >> noise).It is rational to design our device by this parameter sets.
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Latest revision as of 04:04, 27 October 2012

Noise analysis-model

Aim:To figure out whether output is robust when presented with intrinsic noise.

Steps:
1. Use the Gillespie algorithm to perform the stochastic analysis;
2. Draw probability distribution figures (pdf);
3. Compute the noise statistically.

Background:After having determined the parameter range, we would make the noise analysis.According to theoretical predictions, elementary chemical reactions involved in biochemical processes exhibit substantial stochastic fluctuations when low numbers of reactant molecules are involved within the small volume of a living cell. The existence of significant stochastic fluctuations in biochemical processes has been confirmed by numerous experiments including tracking of individual protein molecules in individual cells in gene expression processes[Zhou L, Gregori G, Blackman J,Robinson J, Wanner B (2005) Stochastic activation of the response regulator PhoB by noncognate histidine kinases.J Integrative Bioinformatics 2: 11.] We refer to the most classical Gillespie algorithm and lots of improvements have been made by later generation. For example, Sagar Indurkhya et al mentioned that Dynamic Monte Carlo methods are a common means of simulating the time-evolution of chemical systems.The Gillespie Algorithm (SSA) [1] is the standard algorithm for this process, and has inspired a variety of derivative methods that speed up computation, including the Optimized Direct Method (ODM) [2] and the Next Reaction Method (NRM) [3]. These methods, however, are still computationally costly.Now,we still use the classical algorithm.:

ηij is used to describe the noise, where：

σ ij stands for standard deviation and represents the mean value. If i=j then



The value of noise is ηi2 . If the mean([m]1:1)-mean([m]1:2) >> the value of noise, we identify the output wouldn’t be drown in noise.

Result_Ratio sensor




Fig.1 Pdf means probability distribution frequency



The statistics is given below:





Comparator




Fig.2 Pdf stands for probability distribution frequency.



The statistics is given below:



Conclusion


Both ratio sensor and comparator, the change of mRNA concentration is robust enough when presented with noise(mean([m]1:1)-mean([m]1:2) >> noise).It is rational to design our device by this parameter sets.

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