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− | <div class="topic"><p class="text_color | + | <div class="topic"><p class="text_color">Model Introduction</p></div> |
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− | <div class="topic"><p class="text_color | + | <div class="topic"><p class="text_color">What are we modeling?</p></div> |
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− | <div class="topic"><p class="text_color | + | <div class="topic"><p class="text_color">Model</p></div> |
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+ | <h1> | ||
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<div class="img-container"> | <div class="img-container"> | ||
− | <img src="https://static.igem.org/mediawiki/ | + | <img src="https://static.igem.org/mediawiki/2017/1/12/Model_tcfsh.jpeg" class="main-img" width="100%"> |
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<p class="title">Model Introduction</p> | <p class="title">Model Introduction</p> | ||
− | <p class="content"> | + | <p class="content">Modeling has always played an important role in every field of science. In our project, modeling comes up with real data, and thus makes biological theories easier to be realized and observed. Carl Gauss said, “Mathematics is the queen of the science.” A proposition of mathematics is reliable and indisputable, whereas other science theories have always been at risk of being overthrown. The reason why modeling has a good reputation and a certain status is that it theorems scientific phenomena, and makes them more trustworthy. By conducting modeling, we can have a reasonable embryonic form to formulate a possible solution to a difficult problem. However, the reaction series or the operation mechanism of an unknown equation needs to be reasonably presumed, and this is the most difficult part in the whole process. Inappropriate assumption can lead to erroneous results. Once the right theories are established, we can amend our hypothetical surmise, and build another model. In the modeling process we’ve done, the main technique we used is DE (differential equation). We use derivative to describe the difference of any variables that vary within a very short time. But we’ve encountered some very complicated equations when trying to solve the problem, so we use the program MATLAB to help calculate the results.</p> |
</div> | </div> | ||
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<p class="title">What are we modeling?</p> | <p class="title">What are we modeling?</p> | ||
<p class="content"> | <p class="content"> | ||
− | <br> - The growth of E. coli</br> | + | <br> - The growth of <span style="font-style:italic;">E. coli</span></br> |
<br> - The Expression of Different Color</br> | <br> - The Expression of Different Color</br> | ||
− | <br> - The Concentration Function f:(substance,time)→concentration | + | <br> - The Concentration Function f:(substance,time)→concentration</br> |
<br> - Math Is Long, Life Is Short: Math in Our Life</br></p> | <br> - Math Is Long, Life Is Short: Math in Our Life</br></p> | ||
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<p class="title">Model</p> | <p class="title">Model</p> | ||
<div class="modelingPart"> | <div class="modelingPart"> | ||
− | <h2 class="content-1" id="titleA" style="color:#33FFCC">I. The growth of <span style="font-style:italic;">E. coli</span></h2> | + | <h2 class="content-1" id="titleA" style="color:#33FFCC">I. The growth of <span style="font-style:italic;">E. coli</span> (Click to see more)</h2> |
<div class="modelingPartContent" id="partA"> | <div class="modelingPartContent" id="partA"> | ||
− | <p class="content">At first, we assume that E. coli proliferate and die at the same ratio over time, and the value difference is the birth rate (<span style="font-style:italic;">μ<sub>g</sub></span>). So, we do derivative with this assumption.</p> | + | <p class="content">At first, we assume that <span style="font-style:italic;">E. coli</span> proliferate and die at the same ratio over time, and the value difference is the birth rate (<span style="font-style:italic;">μ<sub>g</sub></span>). So, we do derivative with this assumption.</p> |
<img src="https://static.igem.org/mediawiki/2017/7/7e/Model_1.jpeg" class="bigphoto" width="70%"> | <img src="https://static.igem.org/mediawiki/2017/7/7e/Model_1.jpeg" class="bigphoto" width="70%"> | ||
− | <p class="content">Substituting the boundary condition, <span style="font-style:italic;">t = 0, N = N<sub>0</sub></span>, we then have ∴ e<sup>C<sub>2</sub>-C<sub>1</sub></sup>=N<sub>0</sub> | + | <p class="content">Substituting the boundary condition, <span style="font-style:italic;">t = 0, N = N<sub>0</sub></span>, we then have ∴ e<span style="font-style:italic;"><sup>C<sub>2</sub>-C<sub>1</sub></sup></span>=<span style="font-style:italic;">N<sub>0</sub></span> |
Thus, the equation that expresses the relation between bacteria and time is: | Thus, the equation that expresses the relation between bacteria and time is: | ||
</p> | </p> | ||
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<img src="https://static.igem.org/mediawiki/2017/4/48/Model_2.jpeg" class="bigphoto" width="70%"> | <img src="https://static.igem.org/mediawiki/2017/4/48/Model_2.jpeg" class="bigphoto" width="70%"> | ||
− | <p class="content">By substituting the boundary condition, we then have 𝐶= − 𝑛<sub>𝐿𝐵<sub>0</sub></sub>/𝑘<sub>𝑐𝑜𝑛</sub>−𝑁<sub>0</sub>/𝜇<sub>𝑔</sub> | + | <p class="content">By substituting the boundary condition, we then have <br>𝐶= − 𝑛<sub>𝐿𝐵<sub>0</sub></sub>/𝑘<sub>𝑐𝑜𝑛</sub>−𝑁<sub>0</sub>/𝜇<sub>𝑔</sub></br> |
<br>So the relation between <span style="font-style:italic;">n<sub>LB</sub></span> and <span style="font-style:italic;"><sub>t</sub></span> is: | <br>So the relation between <span style="font-style:italic;">n<sub>LB</sub></span> and <span style="font-style:italic;"><sub>t</sub></span> is: | ||
<img src="https://static.igem.org/mediawiki/2017/e/e4/Model_3.jpeg" class="bigphoto" width="70%"> | <img src="https://static.igem.org/mediawiki/2017/e/e4/Model_3.jpeg" class="bigphoto" width="70%"> | ||
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+ | <p class="content"> </p> | ||
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+ | <img src="https://static.igem.org/mediawiki/2017/5/54/Model_table1.jpeg" class="bigphoto" width="70%"> | ||
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− | <h2 class="content-1" id="titleB" style="color:#44FCCE">II. | + | <h2 class="content-1" id="titleB" style="color:#44FCCE">II. The Expression of Different Color (Click to see more)</h2> |
<div class="modelingPartContent" id="partB"> | <div class="modelingPartContent" id="partB"> | ||
− | <p class="content"> | + | <p class="content-1">Assumption</p> |
− | < | + | <p class="content">1. In order to write the equations down simply, we assume that all the chemical reaction rates are proportional to the concentration of each reagent (e.g. for the reaction: A+B+C→D+E,the forward rate <span style="font-style:italic;">r<sub>+</sub>=k<sub>+</sub>[A][B][C]).</p></span> |
− | < | + | <p class="content">2.For every substances produced by biobricks, we assume that their production rate =<span style="font-style:italic;">φ[mRNA]</span>, <br>[mRNA]= the concentration of the promoted biobrick</br><br>φ= the result of multiplication of rate constant, coefficient of correction (since a biobrick is different from a reagtant), a dimension <span style="font-style:italic;">T<sup>-1</sup></span></br></p> |
− | < | + | |
− | + | <p class="content-1">Equations & Solutions</p> | |
− | </ | + | <img src="https://static.igem.org/mediawiki/2017/8/8c/Equations.png" class="bigphoto" width="70%"> |
+ | <p class="content">According to the picture, we can write down 3 equations as follows:</p> | ||
+ | <img src="https://static.igem.org/mediawiki/2017/c/c4/Modeling5.jpeg" class="bigphoto" width="70%"> | ||
+ | <p class="content">P.S. φ= the result of multiplication of rate constant, coefficient of correction (since a promoter is different from a reagtant), a dimension <span style="font-style:italic;">𝑇<sup>−1</sup></span></p> | ||
+ | |||
+ | <p class="content">By solving these 3 equations, the solution expressed by <span style="font-style:italic;">φ、k and [P<sup>a</sup>]</span> are as follows: | ||
+ | <img src="https://static.igem.org/mediawiki/2017/f/f0/Modeling6.jpeg" class="bigphoto" width="70%"> | ||
+ | |||
+ | <p class="content">When the concentration of each activated promoter reaches to each of their steady state, then we can simplify the equations as follows:</p> | ||
+ | <img src="https://static.igem.org/mediawiki/2017/5/57/Modeling7.jpeg" class="bigphoto" width="70%"> | ||
+ | |||
+ | <p class="content">Besides, since <span style="font-style:italic;">lim<sub>t→∞</sub>(1-1/e<sup>kt</sup>) = 1</span>, satisfying the definition of the horizontal asymptotes. And d(1-1/e<sup>kt</sup>)/dt=ke<sup>-kt</sup>>0 (t∈[0,∞)), so it is a strictly increasing function. | ||
+ | <br>So, this is a strictly increasing and convergent function with an upper bound 1.</br> | ||
+ | <br>Then the result is that the extremum of the concentration is:</br></p> | ||
+ | |||
+ | <img src="https://static.igem.org/mediawiki/2017/e/e8/Modeling8.jpeg" class="bigphoto" width="70%"> | ||
+ | |||
+ | <p class="content-1">Degradation Rate Constant Calculation</p> | ||
+ | <p class="content">As for the other variable written in the solutions, the degradation rate constant, can also be solved with differential equations. Since the degradation rate is an “order one” reaction, the equation can be written as follow:</p> | ||
+ | <p class="content"><span style="font-style:italic;">dM/dt= -k<sub>d</sub>M</span></p> | ||
+ | <p class="content">Then, after solving the equation and substituting the boundary conditions<br><span style="font-style:italic;">(t = 0⇒M = M<sub>0</sub>)</span>, the the solution is:</br></p> | ||
+ | <img src="https://static.igem.org/mediawiki/2017/2/24/Modeling9.jpeg" class="bigphoto" width="70%"> | ||
+ | |||
+ | <p class="content">According to the project 2008 iGEM KULeuven and 2014 iGEM Edinburgh had done, both GFP-LVA and RFP-LVA degrades to half of the amount within 50 to 60 minutes, so we assume that cjblue is the same. The RFP and BFP reference are as follow (the latter degrades to half of the amount about 50 minutes while the former does about 3 hours). So we can get</p> | ||
+ | <img src="https://static.igem.org/mediawiki/2017/e/ef/Modeling10.jpeg" class="bigphoto" width="70%"> | ||
+ | |||
+ | <p class="content">From these degradation rate constants and the relation between concentration and time, the “[cjblue],[RFP],[BFP]-t Diagram” is as follow:</p> | ||
+ | |||
+ | <img src="https://static.igem.org/mediawiki/2017/e/e5/Modeling11.png" class="bigphoto" width="70%"> | ||
+ | |||
+ | <p class="content">According to this simulation diagram, we can know that cjblue and BFP increase faster—coming to 90% of maximum only takes about 3 hours. As for RFP, it takes about 5 hours to reach 70% of maximum, which is also acceptable.</p> | ||
+ | <p class="content">Through mathematical modeling, when observing the sicker changing to a specific color, we can calculate the ratio of each kind of chromoprotein by quantifying it.</p> | ||
+ | <img src="" class="bigphoto" width="70%"> | ||
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</div> | </div> | ||
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− | <h2 class="content-1" id="titleC" style="color:#5BFCD4">III. | + | <h2 class="content-1" id="titleC" style="color:#5BFCD4">III. The Concentration Function (Click to see more)</h2> |
<div class="modelingPartContent" id="partC"> | <div class="modelingPartContent" id="partC"> | ||
− | <p class="content"> | + | <p class="content-1">Equations</p> |
− | <p class="content"> | + | <img src="https://static.igem.org/mediawiki/2017/a/a0/Modelpic.jpeg" class="bigphoto" width="70%"> |
+ | <p class="content">Accroding to their feedback mechanism, we can write down the simultaneous equations as follows.</p> | ||
+ | <img src="https://static.igem.org/mediawiki/2017/f/fc/Modeling12.jpeg" class="bigphoto" width="70%"> | ||
+ | <p class="content">Since the designations are too complex to be written, we change these deignations to simple ones. Meanwhile, we’ll explain all the individual meanings of every designations. (See the following tables)</p> | ||
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+ | <p class="content-1">Designation Description Table</p> | ||
+ | <p class="content">Concentration</p> | ||
+ | <img src="https://static.igem.org/mediawiki/2017/0/08/Modeling13.jpeg" class="bigphoto" width="70%"> | ||
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+ | <p class="content">Constant</p> | ||
+ | <img src="https://static.igem.org/mediawiki/2017/0/00/Formula.jpeg" class="bigphoto" width="70%"> | ||
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+ | <p class="content">Here comes the script.</p> | ||
+ | <img src="https://static.igem.org/mediawiki/2017/e/ea/Ript1.png" class="bigphoto" width="70%"> | ||
+ | <p class="content"> </p> | ||
+ | <img src="https://static.igem.org/mediawiki/2017/8/88/Script2.png" class="bigphoto" width="70%"> | ||
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− | <h2 class="content-1" id="titleD" style="color:#6EFFDB">IV. | + | <h2 class="content-1" id="titleD" style="color:#6EFFDB">IV. Math is Long, Life is Short: Math in Our Life (Click to see more)</h2> |
<div class="modelingPartContent" id="partD"> | <div class="modelingPartContent" id="partD"> | ||
− | <p class="content"> | + | <p class="content">Since it requires complicate and large quantity of computing, you might think mathematics as an unreasonable tool. All it can do is endlessly derivation, and not being able to utilize in the real world. But in fact, mathematics are around us everywhere, while we have not notice them. The following math stuffs will be approachable, including offering formulas, for companies to decide whether they want to use our project; calculate the number of samples, so you can know how much surveys you need to do; offering possible data, give some reference for the team after, etc.</p> |
− | <p class="content"> | + | <p class="content-1">The minimum Number of Cargo Packed in a Box</p> |
− | <p class="content"> | + | <img src="https://static.igem.org/mediawiki/2017/2/24/Modeling14.jpeg" class="bigphoto" width="70%"> |
+ | <p class="content">After having a meeting with Professor Cheng-Ming Chang, we learned that the companies would only like to spend less than 2‰ of the price of the item to guarantee the quality of those item. According to this matter of fact, we can list the following equation:</p> | ||
+ | <img src="https://static.igem.org/mediawiki/2017/b/b9/Modeling15.jpeg" class="bigphoto" width="70%"> | ||
− | + | <p class="content-1">Sample Size Estimation</p> | |
− | < | + | <p class="content">Assume that the data of people‘s habits and opinions roughly obey the form of normal distribution. Then, according to the 68-95-99.7 rule, we can know that at 95% confident level, if we allow a deviation (<span style="font-style:italic;">E</span>), the number of samples we should grab is…</p> |
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+ | <p class="title">Conclusion</p> | ||
+ | <p class="content"> | ||
+ | <br> - Through combining modeling and <a href="https://2017.igem.org/Team:TCFSH_Taiwan/Demonstrate" style="color: orange">device</a>, we are able to design a better application.</br> | ||
+ | <br> - Through mathematical modelling, we can estimate how much LB filled in the sticker is adequate.</br> | ||
+ | <br> - Cjblue and BFP comes to 90% of maximum only takes about 3 hours. As for RFP, it takes about 5 hours to reach 70% of maximum, which is also acceptable.</br> | ||
+ | <br> - When observing the sicker changing to a specific color, we can calculate the ratio of each kind of chromoprotein/fluorescent by quantifying it, even know what time the sticker is activated; when it is exposed to UV or sunlight!</br> | ||
+ | <br> - If you aren’t sure whether the sticker for your product is cost-effective or not, mathematical modelling will be your best solution!</br></p> | ||
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− | <! | + | <!--JS--> |
<script> | <script> | ||
$(function(){ | $(function(){ |
Latest revision as of 03:53, 2 November 2017