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| + | #introvideo {width:480px; length:360px; margin:20px auto; margin-bottom:0;} |
| + | #home {overflow:auto;} |
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| </div> | | </div> |
| <div id="home" class="item"> | | <div id="home" class="item"> |
- | <div class="homepage"> | + | <div id="introvideo"> |
| + | <embed width="480" height="360" quality="high" bgcolor="#000000" name="main" id="main" allowfullscreen="true" allowscriptaccess="always" src="http://www.dnatube.com/nvlab/player/player.swf?config=http://www.dnatube.com/nvlab/econfig.php?key=ddbdf3eff0f505975b6a" type="application/x-shockwave-flash" /></div><div class="homepage"> |
| + | <div id="homecontainer"><h3>Abstract</h3> |
| + | <p>As Synthetic Biology field is on the rise, iGEM also grows up and number of parts in parts registry increase with submission of more complex constructs each year. Our first milestone was to perform more efficient standardization on parts entry due to facing some difficulty while running our algorithms on the parts registry. We also used Software Requirements Specification, Software Design Description and Quality Plan approaches to define requirements for each part and building blocks, risks and design art elements of the designed software program.</p> |
| + | <p>Next, we have used graph theoretic modeling to visualize relations between parts and to standardize representation of the parts as much as possible. It will help us when we try to find input-output relations between either biobrick parts or constructs. By this way, our program BIOGUIDE will act as a guide for searhing biobricks and will provide alternative pathway choices to users for construction of the most reliable devices with respect to given inputs and expected outputs.</p> |
| + | </div> |
| </div> | | </div> |
| </div> | | </div> |
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| <img alt="" src="https://static.igem.org/mediawiki/2010/b/be/Metu-team6.jpg"> | | <img alt="" src="https://static.igem.org/mediawiki/2010/b/be/Metu-team6.jpg"> |
| </div> | | </div> |
- | <p>METU Turkey Software is an interdisciplinary team of 8 students and | + | <p>METU Turkey Software is an interdisciplinary team of 7 students and |
- | 3 advisors from various backgrounds such as Molecular Biology, Bioinformatics, | + | 4 advisors from various backgrounds such as Molecular Biology, Bioinformatics, |
| Computer Engineering and Computer Education and Instructional Technology. | | Computer Engineering and Computer Education and Instructional Technology. |
| We have put our knowledge and experience in our fields together to bring | | We have put our knowledge and experience in our fields together to bring |
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| </div> | | </div> |
| <div class="smallbox" style="margin: 0 auto; float: none"> | | <div class="smallbox" style="margin: 0 auto; float: none"> |
- | <h2 class="black">Muhammad Akif Ağca</h2> | + | <h2 class="black">Muhammed Akif Ağca</h2> |
- | <img src=""> | + | <img src="https://static.igem.org/mediawiki/2010/1/10/Metu-akif2.jpg"> |
| <div class="smalltext"> | | <div class="smalltext"> |
- | <p>Content here</p> | + | <p>In bachelor he has worked on Software Development, Database Management, Instructional Technologies, and Bioinformatics. He was developing the software and leading the team. |
| + | A new page to his life is starting at 2011 after becoming a graduate of Computer Education and Instructional Technologies. He says that " If we can use technology and science efficiently we can solve too many problems in the world, but if can use. That is if we can manage those we can solve the problems and organize the world with minimum problems " which is a study field Science Technology and Management ( STM ) which is the field he will start to work in 2011 ".</p> |
| </div> | | </div> |
| </div> | | </div> |
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| </ul> | | </ul> |
| </div> | | </div> |
- | <div style="height: 250px; background-color:#1e6dd4; padding:10px;"> | + | <div style="height: 250px; background-color: #1e6dd4; padding: 10px;"> |
| <div id="week"> | | <div id="week"> |
| Week 3 and Week 4</div> | | Week 3 and Week 4</div> |
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| </li> | | </li> |
| </ul> | | </ul> |
- | <p> | + | <p>· Design Group</p> |
- | · Design Group</p>
| + | |
| <ul> | | <ul> |
| <li>Team Logo</li> | | <li>Team Logo</li> |
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| </ul> | | </ul> |
| </div> | | </div> |
- | <div style="height: 600px;background-color:#1e6dd4; padding:10px "> | + | <div style="height: 600px; background-color: #1e6dd4; padding: 10px"> |
| <div id="week"> | | <div id="week"> |
| Week 3 and Week 4 | | Week 3 and Week 4 |
- | <p>DOING THE TASKS.</p>
| + | <p>DOING THE TASKS.</p> |
- | </div></div>
| + | </div> |
| + | </div> |
| </div> | | </div> |
| <div class="month"> | | <div class="month"> |
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| </ul> | | </ul> |
| </div> | | </div> |
- | <div style="float: left; width: 540px; height: 170px; font-weight: normal;background-color:#3fff72; padding:10px;"> | + | <div style="float: left; width: 540px; height: 170px; font-weight: normal; background-color: #3fff72; padding: 10px;"> |
| <div id="week"> | | <div id="week"> |
| Week 2, Week 3, & Week 4 | | Week 2, Week 3, & Week 4 |
- | <p>GOOD NEWS Infinite meetings started :) </p>
| + | <p>GOOD NEWS Infinite meetings started :) </p> |
- | <ul>
| + | <ul> |
- | <li>Writing content [shared it, tasks assigned to members
| + | <li>Writing content [shared it, tasks assigned to |
- | according to their fields.]</li>
| + | members according to their fields.]</li> |
- | <li>Software; debugging, testing, adding functions…</li>
| + | <li>Software; debugging, testing, adding functions…</li> |
- | <li>Designers web, poster, presentation, animation,
| + | <li>Designers web, poster, presentation, animation, |
- | importing content…</li>
| + | importing content…</li> |
- | </ul>
| + | </ul> |
- | </div></div>
| + | </div> |
| + | </div> |
| </div> | | </div> |
| <div class="month"> | | <div class="month"> |
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| </div> | | </div> |
| </div> | | </div> |
- | </div> | + | </div><h3>Follow our discussion topic at <a href="http://groups.google.com.tr/group/software_MetuTurkey/topics">our googlegroups</a></h3> |
| + | |
| </div> | | </div> |
| </div> | | </div> |
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| <div class="content2"> | | <div class="content2"> |
| <div class="text"> | | <div class="text"> |
- | <h2>Download</h2> | + | <h2>Download Executable and Code</h2> |
| + | <p>You can download BioGUIDE at <a href="http://sourceforge.net/projects/bioguide">http://sourceforge.net/projects/bioguide</a></p> |
| + | <p>Download & install it and feel it's power!!</p> |
| </div> | | </div> |
| </div> | | </div> |
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| <div class="text"> | | <div class="text"> |
| <h2>Design</h2> | | <h2>Design</h2> |
| + | <a href="https://static.igem.org/mediawiki/2010/6/6a/Metu_Turkey_Software_ER3.jpg"><img src="https://static.igem.org/mediawiki/igem.org/7/71/Metu_Software_ER3.png" /></a> |
| + | |
| </div> | | </div> |
| </div> | | </div> |
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| <div class="content2"> | | <div class="content2"> |
| <div class="text"> | | <div class="text"> |
- | <h2>Code</h2> | + | <h2>User Guide</h2> |
| + | <object width="425" height="344"><param name="movie" value="http://www.youtube.com/v/Znb1o7cr5dc?hl=en&fs=1"></param><param name="allowFullScreen" value="true"></param><param name="allowscriptaccess" value="always"></param><embed src="http://www.youtube.com/v/Znb1o7cr5dc?hl=en&fs=1" type="application/x-shockwave-flash" allowscriptaccess="always" allowfullscreen="true" width="425" height="344"></embed></object><object width="425" height="344"><param name="movie" value="http://www.youtube.com/v/Fk7eJ-Ig_IQ?hl=en&fs=1"></param><param name="allowFullScreen" value="true"></param><param name="allowscriptaccess" value="always"></param><embed src="http://www.youtube.com/v/Fk7eJ-Ig_IQ?hl=en&fs=1" type="application/x-shockwave-flash" allowscriptaccess="always" allowfullscreen="true" width="425" height="344"></embed></object><p>For new users whom want to interest with synthetic biology and for experienced scientists, in our program you have two options for Input Output properties ;</p> |
| + | <p>To find input-output related biobrick parts or larger constructs! If you want to provide specific chemical or physical inputs from external environment, you may choose these inputs from the list. if you want other specific inputs which will be expressed from a coding sequence, the list can provide these specified protein names.</p> |
| + | <img src="https://static.igem.org/mediawiki/2010/6/60/Metu-guide1.jpg"> |
| + | <p>Wanted features of outputs can be selected by either from list or entering individually into text boxes.</p> |
| + | <img src="https://static.igem.org/mediawiki/2010/c/c0/Metu-guide2.jpg"> |
| + | <p>Then click on the “Show Parts ” button.</p> |
| + | <img src="https://static.igem.org/mediawiki/2010/9/95/Metu-guide3.jpg"> |
| + | <p>Then the program will show you the parts have specified I/O properties</p> |
| + | <img src="https://static.igem.org/mediawiki/2010/7/7f/Metu-guide4.jpg"> |
| + | <p>To see the properties of a part just click on it.</p> |
| + | <img src="https://static.igem.org/mediawiki/2010/3/33/Metu-guide5.jpg"> |
| + | <img src="https://static.igem.org/mediawiki/2010/2/27/Metu-guide6.jpg"> |
| + | <p>After clicking, you will see a highlighted pathway on the 2nd graph. Which are the subparts of the clicked part. Showing the sub graph in network.</p> |
| </div> | | </div> |
| </div> | | </div> |
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| <div class="text"> | | <div class="text"> |
| <h2>Human Practices</h2> | | <h2>Human Practices</h2> |
| + | <p>iGEM’s parts registry is the only current database that holds information |
| + | and DNA for over 3000 standard parts for the use of synthetic biology |
| + | community. BioGUIDE is the first designed software that organizes the |
| + | parts in iGEM spring 2010 distribution as possible atomics parts to |
| + | build new biological device and systems for specific input and outputs |
| + | based on graph theory. We are the first group who has applied a novel |
| + | algorithm to search for input/output relations between the parts to |
| + | reveal possible construct assemblies. This new approach will chance |
| + | how the parts registry is used by the scientific community. And the |
| + | availability of software implementing our algorithm with a very user |
| + | friendly graphical user interface will allow all the users of the parts |
| + | registry to explore new and novel constructs according to their parameter |
| + | with ease. Additionally as the BioGUIDE software is an open source ware |
| + | , any user can contribute to the development of the application. So, |
| + | BioGUIDE will be improving with a collaborative effort, which will make |
| + | it even more widely used among the synthetic biologists. </p> |
| + | <p>We also had many collabrations with the teams such as, INSA-Lyon, |
| + | Lethbridge, WashU through our survey and WARSAW as we have participated |
| + | in their survey. Also our sister team METU_TURKEY is our main collaborator. |
| + | They have provided feedback BioGUIDE at different stages of the development. |
| + | And they had the chance to analyze their constructs input/output relations |
| + | throughout this collaboration. </p> |
| + | <p><strong>ALL TEAMS</strong>: The Parts Registry Survey that has been |
| + | developed by METU_TURKEY_SOFTWARE got response from 253 of participant |
| + | from 94 teams. Analysis of the survey results we have received so far |
| + | indicates that we were able outreach to the iGEM community and help |
| + | them verbalize their concerns and suggestions for the parts registry |
| + | standards and the maintenance of the database.</p> |
| + | <p><strong>WARSAW</strong>: Our team members have participated in their |
| + | survey abour iGEM participants profile. </p> |
| + | <p><strong>METU_TURKEY</strong>: Beta testing of the algorithm developed |
| + | and the BioGUIDE software has been performed by METU_TURKEY on few case |
| + | studies. Additionally they have tested their construct for 2010 competition |
| + | with our algorithm. </p> |
| </div> | | </div> |
| </div> | | </div> |
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| <div class="text"> | | <div class="text"> |
| <h2>Material</h2> | | <h2>Material</h2> |
| + | <p>Our main data source for BIO Guide Software Program was the available |
| + | background information of parts distributed in 2010 iGEM plates (Total |
| + | of three384-well plates of dried DNA) to the wetlab teams. This data |
| + | was available through both the parts registry main website (<a href="http://partsregistry.org/Main_Page">http://partsregistry.org/Main_Page</a>) |
| + | in XML format and parts registry libraries (http://partsregistry.org/assembly/libraries.cgi?id=31) |
| + | in Excel format. Data from parts with specific part IDs have been parsed |
| + | with a custom code developed to modify SAX Parser. Then, the rest of |
| + | the data which needs to be standardized according to biological importance |
| + | have been extracted from the Registry of Parts Page manually. The chemical |
| + | (IPTG, galactose etc.) or physical (UV irradiation, temperature etc) |
| + | external inputs and proteins synthesized from a biobrick coding sequence |
| + | can affect promoters on the parts. These effectors are identified under |
| + | the title “Input”. And the “Output” s of these effectors are classified |
| + | as inducers (a molecule that starts gene expression), repressors (blocker |
| + | of attachment of RNA polymerase to promoter), activators (increasing |
| + | the rate of transcription) and inhibitor s(decreasing the rate of transcription). |
| + | These standardizations on the database helped us to build the algorithm |
| + | based on input/output relationships. MySQL Server is used for Database |
| + | development and organization. All of our illustrations for ER and algorithm |
| + | is created in SmartDraw (trial version). Java Programming Language, |
| + | and NetBeans Development environment is used or for software development. |
| + | The graphical visualization of the software is done with Cyctoscape |
| + | and yfiles libraries (trial version) are used for the presentation of |
| + | graphical events. We have utilized css Javascripts for our webdesign. |
| + | Autodesk Maya 2011 with Academic Licence, Adobe Creative Suite 5 Master |
| + | Collection (Trial Version) have been used for animations and illustrations. |
| + | Video tutorial for the BioGUIDE has been created by camstudio and trial |
| + | versions of Flash and After Effects are also used for the videos. |
| + | </p> |
| </div> | | </div> |
| </div> | | </div> |
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| <div class="content2"> | | <div class="content2"> |
| <div class="text"> | | <div class="text"> |
- | <h2>User Guide</h2> | + | <h2>Supporting Tools</h2> |
| + | <ul> |
| + | <li>SAX Parser ( modified )to parse XML files</li> |
| + | <li>Java ProramingLanguage, NetBeans Developement environment for |
| + | software developement</li> |
| + | <li>MySQL Server for DataBase</li> |
| + | <li>cystoscape for graph visualization</li> |
| + | <li>yfiles library for graph events</li> |
| + | <li>SmartDraw for illutration of ER and Algorithm</li> |
| + | <li>maya & Cinema 4D for 3D animation, Adobe Master Collection and |
| + | Microsoft Expression Studio for design</li> |
| + | <li>CSS, Java Script for web</li> |
| + | </ul> |
| </div> | | </div> |
| </div> | | </div> |
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| <div class="text"> | | <div class="text"> |
| <h2>Safety</h2> | | <h2>Safety</h2> |
| + | <p>Synthetic biology has the potential to impact many areas of society. |
| + | Synthetic biologists may use artificial molecules to reproduce emergent |
| + | behavior from natural biology, with the goal of creating artificial |
| + | life or seeking interchangeable biological parts to assemble them into |
| + | devices and systems that function in a manner not found in nature (Benner |
| + | and Sismour 2005, Endy 2005, Heinemann and Panke 2006, Luisi 2007, Serrano |
| + | 2007).There is possibility of causing intentional or accidental harm |
| + | to humans, agriculture or the environment. While deliberate damage is |
| + | dealt with under the heading biosecurity, the potential unintended consequences |
| + | have to be considered under the term biosafety. As a software developer |
| + | , we have to consider all possible maliciously use of synthetic biology |
| + | tools. However, it is diffucult to understand for which purposesour |
| + | tools will be used, bestway avoiding garage bioterrorism is all parts |
| + | before adding to partsregistry must be checked , looked for toxic affect |
| + | and any environmental or human harmness. After scanning possible candidate |
| + | parts, a committe should decide whether novel part can be added parts |
| + | registry or not.And we can only warn the user about our intention while |
| + | building the application: </p> |
| + | <p>“BioGUIDE v1.0 software is <strong>FOR RESEARCH USE ONLY</strong>, |
| + | no medical or diagnostic use for applications of the novel Biobrick |
| + | constructs generated through our software has been described “</p> |
| + | <p>“No military (defense or combat) applications will be allowed in |
| + | future”</p> |
| </div> | | </div> |
| </div> | | </div> |
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| <div class="content2"> | | <div class="content2"> |
| <div class="text"> | | <div class="text"> |
- | <h2>Supporting Tools</h2> | + | <h2>Contact</h2> |
| + | <p>For critics, suggestion, or appraisal, you can contact us on |
| + | <a href="mailto:software_metuturkey@googlegroups.com">software_metuturkey@googlegroups.com</a></p> |
| </div> | | </div> |
| </div> | | </div> |
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| <div class="text"> | | <div class="text"> |
| <h2>Future Plan</h2> | | <h2>Future Plan</h2> |
| + | <p>The application we have developed can be used by all iGEM members. |
| + | As the iGEMs database expands and the recognition of the field of Synthetic |
| + | Biology increases, data resources from other biological databases such |
| + | as NCBI might be needed to be integrated to the application. In such |
| + | a situation, extendibility of the application is vital. New data resources |
| + | and new functions should be added easily. </p> |
| + | <p>Before planning ahead, feedback from other teams and iGEM headquarters |
| + | about the BioGuide 1.0 will be collected. That will help us to fill |
| + | in the missing features of the application and check the theories which |
| + | are basis of our algorithms. </p> |
| + | <p>As our application is not geared towards any commercial use and will |
| + | stay as an academic application, keeping track of the weekly developmental |
| + | process on the wiki notebook environment was satisfactory. If the need |
| + | for a commercial application emerges, we should be utilizing professional |
| + | software development approaches to determine the exact requirements |
| + | and to facilitate the use of a common language between interdiciplinary |
| + | members in the team. </p> |
| + | <p>For constructing BioGuide 2.0 we have some plans. </p> |
| + | <h3>Short Term plan:</h3> |
| + | <p>Next year we are planning to generate BioGuide 2.0 by using all parts |
| + | data but inorder to do this we will update our part database but easyway |
| + | is standardization and reorganizing all parts in partsregistrty.org |
| + | according to our suggestion because re-organizing and normalization |
| + | are crucial. We are planning to add new tools to improve graphs.Our |
| + | ultimate aim is finding best pathway based on automated construction |
| + | and input-output relation. BioGuide 2.0 will be more faster because |
| + | we are planning to use OODBMS and all all platform will support BioGuide |
| + | 2.0. </p> |
| + | <h3>Long term plan:</h3> |
| + | <p>We want to improve our algoritm and add more parameter to make graphs |
| + | more effective. Our dream is embeding our software into partsregistry.org |
| + | so no mere iGEMers will choose parts in real time by using our software. |
| + | </p> |
| + | <h3>Suggestions based on PartsRegistry Survey Results</h3> |
| + | <p>First suggesiton is offering fartnership with Google for easy search |
| + | and founding a committe to enforce a standardized nomenclature for terminology |
| + | and parts registry entries. </p> |
| + | <p>We strongly suggest starting a forum on how to quantify the performance |
| + | of promoters and genes to bring an easy to measure standard for the |
| + | efficiency of the parts. Additionally iGEM should assume the responsibility |
| + | and provide the measurements for the each promoter and gene included |
| + | in the distributions. The second choice would beeven better in terms |
| + | of standardization as all the measurement will be performed by one center |
| + | under similar conditions and with experienced researchers, which will |
| + | allow user to compare and contrast the efficiencies of the parts more |
| + | accurately. We suggest excluding the parts not-working, low rated or |
| + | with negative feedbacks from the annual distribution plates but still |
| + | archive them and make their data available through the parts registry. |
| + | So the while the individuals labs are receiving plates with higher rated, |
| + | fully working parts for their projects, anyone who wants to work on |
| + | a more exotic part can search through the achieves and re-vitalize the |
| + | parts stored there. The challenge of re-vitalization of parts can be |
| + | encouraged as an collaborative effort. We are sure, all of us would |
| + | like to see gene-protein and pathway information if these information |
| + | was integrated into the database and offered automatically for each |
| + | entry in the database. We are planning to provide this information about |
| + | the parts to all parts registry users as a build-in option in the next |
| + | version of BioGuide in iGEM 2011. </p> |
| </div> | | </div> |
| </div> | | </div> |
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- | <h2>Contact</h2>
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- | </div>
| |
| </div> | | </div> |
| <div class="item"> | | <div class="item"> |
| </div> | | </div> |
- | <div class="clear"> | + | <div id="miscellaneous5" class="item"> |
| + | <div class="content2"> |
| + | <div class="text"> |
| + | <h2>Sponsors</h2> |
| + | <ul id="sponsorlist"> |
| + | <li><img src="http://tecrubem.net/wp-content/uploads/2009/09/tubitak.jpg" width="200" height="200"></li> |
| + | <li><img src="https://static.igem.org/mediawiki/igem.org/0/06/METU-Surat.jpg"></li> |
| + | <li><img src="https://static.igem.org/mediawiki/igem.org/6/64/Teknokent.jpg"></li> |
| + | <li><img src="https://static.igem.org/mediawiki/igem.org/d/d8/Sentegen.jpg"></li> |
| + | </ul> |
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- | <div class="text">
| |
- | <h2>Algorithm</h2>
| |
- | <p>In this section, the step by step functioning of our application,
| |
- | along with the encapsulation of the algorithmic concepts of ‘standardization’
| |
- | of functional iGEM devices are depicted in pictorial forms called flowcharts.
| |
- | Rectangular boxes represent the encapsulation of implementations of
| |
- | the computer programs to perform the particular tasks stated in that
| |
- | box on the flowcharts. These boxes are sometimes called subprograms,
| |
- | objects or packages in Object Oriented software Engineering context.
| |
- | The diamonds represent decision branching and they are found between
| |
- | two rectangular boxes. The arrows show the direction in which subprograms
| |
- | work and communicate. The subprogram at the head of the arrow starts
| |
- | executing after the termination of the subprogram at the tail of the
| |
- | arrow. Following flowcharts are the high level representations of our
| |
- | algorithms developed for the BioGuide software.</p>
| |
- | <br>
| |
- | <h3>1</h3>
| |
- | <img src="https://static.igem.org/mediawiki/2010/9/95/Metu-algorithm1.png" />
| |
- | <p><span>Diagram 1. Flowchart of collection, formatting and storage
| |
- | of devices data algorithm</span></p>
| |
- | <p>Information about the iGEM parts had to be collected in a standardized
| |
- | format for our application to function properly. Following data collection
| |
- | custom subprograms is needed to parse and forward the data the application’s
| |
- | database. In order to achieve this we have designed and implemented
| |
- | the algorithm shown in diagram 1. In this algorithm, the first stage
| |
- | was to find the list of part IDs of devices which were supplied by iGEM
| |
- | in Spring 2010 distribution. This information has been collected from
| |
- | two sources 1) plate files in excel format which was available online
| |
- | 2) device data provided in xml format, both provided by iGEM. The last
| |
- | step in the algorithm was to send the collected partID data to the application’s
| |
- | database.</p>
| |
- | <br>
| |
- | <h3>2.</h3>
| |
- | <img src="https://static.igem.org/mediawiki/2010/e/e6/Metu-algorithm2.png" />
| |
- | <p><span>Diagram 2. Flowchart for BioGuide execution before and during
| |
- | user interaction</span></p>
| |
- | <p>Diagram 2 presents the main algorithm, which shows how BioGuide application
| |
- | works. In BioGuide the major components are device and Biobrick graphs.
| |
- | While the device graph represents input-output (promoter-regulator)
| |
- | compatibility combination of iGEM devices, the Biobrick graph represents
| |
- | combinations of atomic parts assembled in a device or system. The flowchart
| |
- | shows how these graphs are created and embedded into the program, which
| |
- | displays both of the graphs to the user when launched. Application presents
| |
- | few interactive options to the user when started, which were shown on
| |
- | the flowchart under the horizontal, bolded line. As shown on the diagram
| |
- | 2, there are four interactive tasks BioGuide can do, where the device
| |
- | and Biobricks graphs are utilized. Upon clicking a node on a devices
| |
- | or Biobricks graph, that node changes in size and color and the various
| |
- | functions shown on the flowchart can be performed then after.</p>
| |
- | </div>
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- | <div class="content2">
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- | <div class="text">
| |
- | <h2>Modeling</h2>
| |
- | <h3>Graphical Modeling for Bio-Guide</h3>
| |
- | <h4>Introduction</h4>
| |
- | <p>Graphical Modeling Theory has been applied to construct four different
| |
- | graphs where relations of atomic parts, devices and systems and the
| |
- | functional combinations that can build new constructs are presented
| |
- | for the iGEMs parts registry database. Three graphs are composed of
| |
- | iGEM devices and one graph is based on Biobricks. Each graph comprises
| |
- | a set of vertices or nodes and a set of edges. In the set of nodes each
| |
- | node represents a device, while in the set of edges each edge represents
| |
- | the input-output combination of the nodes. These graphs are directed
| |
- | graphs as the edges are created according to input-output combination.
| |
- | All compatibilities between a regulator and a promoter of an edge is
| |
- | created, where the source of this edge is the device with the corresponding
| |
- | regulator and target of the edge is the device with the promoter in
| |
- | concern.</p>
| |
- | <img src="https://static.igem.org/mediawiki/2010/3/3f/Metu-node1.png" />
| |
- | <p><span>Fig. 1: A node representing a device</span></p>
| |
- | <img src="https://static.igem.org/mediawiki/2010/1/14/Metu-node2.png" />
| |
- | <p><span>Fig. 2: Arrow representing an edge between two nodes</span></p>
| |
- | <p>The atomic structures used in our graphical model have been represented
| |
- | in Figures 1 and 2. A node is represented with a solid circle where
| |
- | the label, the part/device ID according to iGEM standards, of the device
| |
- | is marked on the foreground. The blue arrows between nodes connect the
| |
- | related devices, representing the input-output connectivity. End style
| |
- | of the arrow helps us to determine the direction of the node, like in
| |
- | Figure 2 where the node labeled BBa_S03520 is the source and BBa_JO9250
| |
- | is the target.</p>
| |
- | <br>
| |
- | <h3>Directivity</h3>
| |
- | <p>All the four constructed graphs build for BioGuide are directed graphs.
| |
- | So that, for every edge there must be a single source and a target.
| |
- | There is no single edge which is bidirectional. In mathematical form
| |
- | this can be represented as:</p>
| |
- | <p>If an edge e has node v as source and node w as target then the edge
| |
- | can be expressed as</p>
| |
- | <img src="https://static.igem.org/mediawiki/2010/6/6c/Metu-equation1.png" />
| |
- | <p>For a directed graph the combination (v, w) is totally different
| |
- | from (w, v). Therefore,</p>
| |
- | <img src="https://static.igem.org/mediawiki/2010/a/ac/Metu-equation2.png" />
| |
- | <p>The direction of the edges has been represented with the arrows,
| |
- | as explained in Figure 2.</p>
| |
- | <br>
| |
- | <h3>Connectivity</h3>
| |
- | <p>The nodes forming their own sub-graphs disconnected from the rest
| |
- | of the nodes have been recognized, which showed us the presence of incompatibility
| |
- | between few regulators and promoters of the devices. We have observed
| |
- | this disconnection in all four of our graphs. The basis of the disconnection
| |
- | has been shown in Figure 3, where the two sub-graphs without any edge
| |
- | that connects them to the main graph has been presented on the right
| |
- | hand side of the diagram. These features classify our graphs as disconnected
| |
- | graphs [1].</p>
| |
- | <img src="https://static.igem.org/mediawiki/2010/8/8b/Metu-node3.png" />
| |
- | <p><span>Fig. 3: A zoomed in screenshot showing two sub-graphs within
| |
- | the disconnected graph.</span></p>
| |
- | <br>
| |
- | <h3>"Semi-Simplicity"</h3>
| |
- | <p>A simple graph is a graph in which no more than one edge contains
| |
- | the same set of nodes. So, in a simple graph it is not possible to find
| |
- | more than one edge with the same source and the same target. Additionally,
| |
- | an edge with the same source and target, forming a loop is not allowed.
| |
- | But, in synthetic biology it is possible to construct a device consisting
| |
- | of devices or bio bricks of the same species or type. Accordingly, our
| |
- | graphs are simple graphs with an exception of possible self-containing
| |
- | loops, where the edge starts from and ends on the same node. Our graphs
| |
- | have an exception of having loops and due to this permitted flexibility
| |
- | our graphs are "semi-simple".</p>
| |
- | <p>For general information about graphs refer to:</p>
| |
- | <p><span><a href="http://en.wikipedia.org/wiki/Graph_(mathematics)">
| |
- | [1] http://en.wikipedia.org/wiki/Graph_(mathematics)</a></span></p>
| |
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| |
- | </div>
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- | <div id="project8" class="item">
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- | <div class="content2">
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- | <div class="text">
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- | <h2>Results</h2>
| |
- | </div>
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- | </div>
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- | </div>
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- | <div class="item">
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- | </div>
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- | </div>
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- | d
| |
- | with the functional properties of parts.</span></p>
| |
- | <p>Third part of our standardization template includes parameters of
| |
- | contingent input and output elements. These parameters are classified
| |
- | into two groups for simplicity as presented on Table 3. This final part
| |
- | of the standardization template includes the upmost important information
| |
- | about the Biobricks that are required for the BioGuide Software to run
| |
- | its searching algorithm.</p>
| |
- | <p>Briefly, BioGuide application is designed to catch the input and
| |
- | output relations of individual parts to examine possible Biobricks pathways
| |
- | for specific input and output queries. In other words, at pre-experimental
| |
- | stage, it helps wet lab biologists to design their unique constructs
| |
- | by revealing possible alternative options for pre-determined purposes,
| |
- | along with the primary paths. Our ultimate goal is to improve the algorithm
| |
- | designed for iGEM 2010 and present a new version of the BioGuide in
| |
- | iGEM 2011, which will provide optimum design of constructs for predetermined
| |
- | parameters.</p>
| |
- | <p>Most of the parts are composed of functional and nonfunctional constructs
| |
- | which are formed by atomic parts. And every part should carry the information
| |
- | for all of its atomic parts within itself. The “input” heading actually
| |
- | stands for promoters. Parts with one or more promoters can be found
| |
- | at iGEM’s Parts Registry. Along with the information on which and how
| |
- | many promoters a part might have, the activity level of promoters are
| |
- | also important to distinguish between a constitutively active promoter
| |
- | or a promoter activated by specific physiological processes or states
| |
- | etc. This information was crucial for us to dissect in order to run
| |
- | our algorithm as it directly affects which inputs can activate the devices
| |
- | or the systems.</p>
| |
- | <p>Throughout our investigations on the Parts Registry, we found out
| |
- | that much of the terminology was being used ambiguously. Although this
| |
- | might not be vital for synthetic biologists, it is still endeavoring
| |
- | to understand the function of certain regulatory elements which also
| |
- | becomes a time consuming task for the researcher. Thus, we recommend
| |
- | that the explanations of certain regulatory elements should be redefined
| |
- | and fixed especially for synthetic biology for easy communication, sharing
| |
- | and searching of information.</p>
| |
- | <p>Common misuses of the terminology can guide us to figure out how
| |
- | to construct a standard nomenclature for synthetic biology. We claim
| |
- | that a standard nomenclature is urgently needed for synthetic biology
| |
- | for the following reasons. First of all, synthetic biology is an emerging
| |
- | research discipline and an industrial application area which is highly
| |
- | promising. Secondly, redefinition of the terminology to build a standard
| |
- | nomenclature is needed as some of the terms are prone to be used instead
| |
- | of another causing problems related to misuse for the global communication
| |
- | about synthetic biology. Lastly, the nomenclature has major importance
| |
- | for the construction of a persistent and trustworthy database for synthetic
| |
- | biology which serves for the information exhibition and exchange globally.
| |
- | For instance, there are obvious misunderstandings about the words which
| |
- | are predominantly used for regulation process. We have noticed that,
| |
- | the terms “inhibitor” and “repressor” are being used as equivocally
| |
- | in the part information pages. Like the lactose inhibitor protein, a
| |
- | widely used DNA-binding transcriptional repressor, that have been labeled
| |
- | both as “inhibitor” and “repressor” at iGEM’s Parts Registry. Similar
| |
- | problems resulting from ambiguous use of terminology also observed with
| |
- | regulatory elements. To sum up, we investigated all input elements for
| |
- | promoters and classify these elements in terms of their function, affect
| |
- | and required input element for them. So, we suggest that terminology
| |
- | used for regulation of transcription should be defined clearly on iGEM’s
| |
- | website and correct use of terminology should be enforced.</p>
| |
- | <p>The second group of parameters was collected under the title “Output”,
| |
- | which refers to products of functional genes. In contradiction, the
| |
- | term “reporter” has also been described within the same list. Reporters
| |
- | are also genes whose products, can be used for screening as an output.
| |
- | According to our group, the usage of the term “reporter” for genes is
| |
- | unnecessary and cause extra complexity for information distribution
| |
- | and gives rise to discrepancies. Instead of using the term “reporter”,
| |
- | predefined “gene” description should be used for genes, which can function
| |
- | as reporters. The special information which is related with the characteristic
| |
- | of that gene should also be presented on part info web page.</p>
| |
- | <p>Furthermore, the same terminology “reporter” was used for both atomic
| |
- | parts and composite bio-bricks. Also the overall image descriptions
| |
- | for these were defined as “reporters”. We want to point out that using
| |
- | same nomenclature for both atomic genes and for whole functional constructs
| |
- | contributes to the complexity and makes specific explorations difficult
| |
- | through the Parts Registry. So, assigning “reporter” for both atomic
| |
- | parts and for whole constructs is not a good practice. Instead, we are
| |
- | suggesting the usage of other available terminology for the parts listed
| |
- | as reporters, which most of the constructs, now known as reporters,
| |
- | can be grouped into, such as “protein generators”, “composite parts”
| |
- | or “inverters”.</p>
| |
- | <p>Devices are whole constructs which are functional and have specific
| |
- | and distinct functions. But, as we have observed, unfortunately, the
| |
- | term “device” is also being used for parts which are not functional
| |
- | and do not have specific functional at all. Moreover, within the classification
| |
- | of devices, we argue that some terms are also being used unnecessarily
| |
- | and ambiguously. Devices are classified into five types which are protein
| |
- | generators, reporters, inverters, receivers and senders, measurement
| |
- | devices. For example iGEM defines protein generators as:</p>
| |
- | <p>Protein generator = promoter + rbs +gene + terminator</p>
| |
- | <p>Though we accept the definition for protein generators, we observed
| |
- | that there exist numerous parts which are defined as protein generators
| |
- | but actually most of them do not fit to the definition provided above.
| |
- | Although some parts are not functional and do not generate proteins
| |
- | at all, they are classified as protein generators, which makes searching
| |
- | for the parts difficult in the registry. Furthermore, there are also
| |
- | numerous parts which are defined as “composite parts” but actually they
| |
- | fit to the same definition with protein generators. In order to overcome
| |
- | the problem of misuse of device type we have extracted related image
| |
- | ID information for the composite parts. Image ID information helped
| |
- | us to correctly categorize composite parts depending on its individual
| |
- | atomic parts and identify the ones with more than one function, such
| |
- | as being both inhibitor and activator. In other words, we used image
| |
- | and part IDs in order to merge an input for its outputs.</p>
| |
- | <p>Subtitle working conditions, includes all the detailed information
| |
- | about the experimental properties of parts, and the details about the
| |
- | working process of individual parts and complete devices. Additionally,
| |
- | we marked the subtitle “Working Condition” in our standardization template
| |
- | as potentially the most important title that helps synthetic biologist
| |
- | to better understand the parts functions at iGEM’s part registry database.
| |
- | The main problem we have encounter with the subtitle “working condition”
| |
- | is within most of the parts the details about working process is not
| |
- | enough and not provided regularly. </p>
| |
- | <br>
| |
- | <h3>Examples of Misuse of Terminology:</h3>
| |
- | <h4>For Composite Parts:</h4>
| |
- | <p>PartID: BBa_S04055</p>
| |
- | <p>PartName: Synthetic lacYZ operon</p>
| |
- | <img src="https://static.igem.org/mediawiki/2010/a/ac/Metu-database1.png" />
| |
- | <p>This part is functional and responsible for the production of LacY
| |
- | and LacZ proteins. This part partially fits the definition for “composite
| |
- | part” but actually should be a protein generator as it fits fully to
| |
- | the definition of “protein generators”.</p>
| |
- | <h4>For Protein Generators:</h4>
| |
- | <p>PartID: BBa_J45299</p>
| |
- | <p>PartName: PchA & PchB enzyme generator</p>
| |
- | <img src="https://static.igem.org/mediawiki/2010/2/2c/Metu-database2.png" />
| |
- | <p>The part which is illustrated above actually fits the definition
| |
- | for “composite part” but in part registry it is classified as protein
| |
- | generator. This part can be functional but it needs a promoter. Even
| |
- | though this part is not functional and is not capable of producing protein,
| |
- | part registry assigns this product as protein generator. We suggest
| |
- | that all parts in the registry, which are composed of more than one
| |
- | atomic part and which are not functional on their own but can be functional,
| |
- | should be classified as “composite parts”.</p>
| |
- | <h4>For Reporters:</h4>
| |
- | <p>PartID: BBa_J04451</p>
| |
- | <p>PartName: RFP Coding Device with an LVA tag</p>
| |
- | <img src="https://static.igem.org/mediawiki/2010/0/0a/Metu-database3.png" />
| |
- | <p>This functional part is classified as “Reporter” in the parts registry
| |
- | database. It is very clear that this part fits the same description
| |
- | as Protein Generator in Biobrick part registry standards. Although,
| |
- | this part has specific and known functional role, characterizing this
| |
- | part as a reporter is unnecessary and contributes to the level of complexity
| |
- | of information provided. Instead, we suggest that this part should be
| |
- | classified as “protein generator” and related detailed information about
| |
- | the specific function of this part, should be provided in the part information
| |
- | page.</p>
| |
- | <p>In conclusion, as mentioned above we tried to reorganize and normalize
| |
- | the information about parts which is provided in part registry for 2010
| |
- | in order to develop our algorithm for the BioGuide application. During
| |
- | this process, we encountered some inconsistencies and misuses of the
| |
- | terminology being used and also inadequacies about the information provided
| |
- | about parts. First of all, we claim that a standard nomenclature should
| |
- | be constituted for future use in the field of synthetic biology. Based
| |
- | on the information gathered according to new nomenclature a professional
| |
- | database should be constructed to address the needs of synthetic biology.
| |
- | This will enable easy information exchange and exhibition globally.
| |
- | Secondly, although there are enough information about parts exists on
| |
- | parts registry database, the information which is provided for parts
| |
- | need to be ordered urgently. Furthermore, there should be new experimental
| |
- | standards which must be introduced to groups in the part submission
| |
- | process for the subtitle “working condition”. These experimental standards
| |
- | will be important because the experimental details about parts are not
| |
- | satisfying the needs of wet-lab biologists for the design and the construction
| |
- | of new Biobricks.</p>
| |
- | </div>
| |
- | </div>
| |
- | </div>
| |
- | <div class="item">
| |
- | </div>
| |
- | <div id="download5" class="item">
| |
- | <div class="content2">
| |
- | <div class="text">
| |
- | <h2>Contact</h2>
| |
- | </div>
| |
- | </div>
| |
- | </div>
| |
- | <div class="item">
| |
| </div> | | </div> |
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| <div class="content2"> | | <div class="content2"> |
| <div class="text"> | | <div class="text"> |
- | <h2>Modeling</h2> | + | <h2>Graph Modeling</h2> |
| <h3>Graphical Modeling for Bio-Guide</h3> | | <h3>Graphical Modeling for Bio-Guide</h3> |
| <h4>Introduction</h4> | | <h4>Introduction</h4> |
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| <div class="text"> | | <div class="text"> |
| <h2>Results</h2> | | <h2>Results</h2> |
| + | <ul> |
| + | <li>In order to develop BioGuide algorithm, there was a need to |
| + | reorganize and normalize parts information database in partsregistry.org. |
| + | Information of the parts was processed and developed from partsregistry.org |
| + | which includes the PartID, PartName, RFC values, etc , designer |
| + | and contact information and parameters to build a standardized template |
| + | for our algorithm to run smoothly. </li> |
| + | <li>Database standardization is done by analyzing iGEM Spring 2010 |
| + | distribution and collecting information needed for the standardized |
| + | parts. Also new parameters are assigned according to parts input-output |
| + | model like : Inducer, Activator, Repressor, Inhibitor</li> |
| + | <li>For each promoter we have assigned their inducers or repressors |
| + | as input and for protein generator parts we have assigned generated |
| + | proteins as output which maybe activator or repressor of other devices. |
| + | </li> |
| + | <li>iGEM devices are depicted in pictorial forms called flowcharts, |
| + | encapsulation of implementations , decision branching and direction |
| + | are milestones of our algorithm. Following flowcharts are the high |
| + | level representations of our algorithms developed for the BioGuide |
| + | software.</li> |
| + | <li>We run our algorithm on the real combination dataset in order |
| + | to build our input/output relations graphs. We also collected the |
| + | subpart assembly order, such as 1st: promoter, 2nd:rbs, 3rd:coding |
| + | seq, any internal parts and the Last: terminator. Each specific |
| + | Biobrick type has been assigned a number as a unique image ID from |
| + | 1 to 19. </li> |
| + | <li>ImageID assembly orders for each construct have been used to |
| + | extract the type information for each subpart with that construct. |
| + | This innovative approach helped us to reveal 400 possible brick |
| + | combinations present within the 3x384 well plates distributed by |
| + | iGEM in Spring 2010</li> |
| + | <li>Four different graphs were constructed based on graphical modeling |
| + | theory where relations of atomic parts, devices and systems and |
| + | the functional combinations that can build new constructs are presented |
| + | for the iGEMs parts registry database. Three graphs are composed |
| + | of iGEM devices and one graph is based on Biobricks.</li> |
| + | <li>Each graph comprises a set of vertices or nodes and a set of |
| + | edges. In the set of nodes each node represents a device, while |
| + | in the set of edges each edge represents the input-output combination |
| + | of the nodes.</li> |
| + | <li>We arrange a survey to analyze user needs and response, According |
| + | to our survey results, 244 participants are completed our survey |
| + | between 10 to 22.10.2010, 57% of the participant had scientific |
| + | degrees from B.Sc to Professor and 18% had graduate degrees. 18% |
| + | of participants are enrolled in their teams as either Instructors |
| + | or Advisors.INSA-Lyon, Lethbridge, WashU are dedicated as collaborators |
| + | with more than 60% team participation. You can learn more on survey |
| + | results on our collaboration page</li> |
| + | </ul> |
| </div> | | </div> |
| </div> | | </div> |
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- | <li>
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| + | |
- | <a class="panel" href="#team">Team</a></div>
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- | </li>
| + | |
- | <li>
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- | <div class="menutop menusingle panel">
| + | |
- | <a class="panel" href="#motivation">Motivation</a></div>
| + | |
- | </li>
| + | |
- | <li>
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- | <div class="menutop menusingle panel">
| + | |
- | <a class="panel" href="#scope">Scope</a></div>
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- | <div class="menutop">
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- | <a class="panel" href="#project">Project</a><div class="toggle toggle-closed">
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- | <ul class="submenu">
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- | <li><a class="panel" href="#project">Introduction</a></li>
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- | <li><a class="panel" href="#project2">Design</a></li>
| + | |
- | <li><a class="panel" href="#project3">Material</a></li>
| + | |
- | <li><a class="panel" href="#project4">Methods</a></li>
| + | |
- | <li><a class="panel" href="#project5">Database Standardization</a></li>
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- | <li><a class="panel" href="#project6">Algorithm</a></li>
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- | <li><a class="panel" href="#project8">Results</a></li>
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- | <div class="menutop panel">
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- | <a class="panel" href="#download">Download</a><div class="toggle toggle-closed">
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- | +</div>
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- | </div>
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- | <ul class="submenu">
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- | <li><a class="panel" href="#download">Executable</a></li>
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- | <li><a class="panel" href="#download2">Code</a></li>
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- | <li><a class="panel" href="#download3">User Guide</a></li>
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- | <div class="menutop panel">
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- | <a class="panel" href="#miscellaneous">Miscellaneous</a><div class="toggle toggle-closed">
| + | |
- | +</div>
| + | |
- | </div>
| + | |
- | <ul class="submenu">
| + | |
- | <li><a class="panel" href="#miscellaneous">Collaboration</a></li>
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- | <li><a class="panel" href="#miscellaneous2">Human Practices</a></li>
| + | |
- | <li><a class="panel" href="#miscellaneous3">Safety</a></li>
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- | <li><a class="panel" href="#miscellaneous4">Future Plan</a></li>
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- | </ul>
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- | </ul>
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- | </div>
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- | </body>
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- | | + | |
- | </html>
| + | |
- | lab
| + | |
- | biologists.</p>
| + | |
- | <p>Without a question there is an urgent need to build a distinct and
| + | |
- | specific database well organized with its own standards for synthetic
| + | |
- | biology; however, development of such a database is not an easy task.</p>
| + | |
- | <br>
| + | |
- | <h3>Contact Information of Part Owners and Qualitative Group Comments
| + | |
- | about Parts</h3>
| + | |
- | <p>=========================================</p>
| + | |
- | <p>Designers: Mail:</p>
| + | |
- | <p>GroupFavorite:</p>
| + | |
- | <p>StarRating:</p>
| + | |
- | <p>Parameters:</p>
| + | |
- | <p>=========================================</p>
| + | |
- | <p><span>Table 2: The above table simply depicts information about possessors
| + | |
- | of parts and their contact information and the popularity of the parts
| + | |
- | for groups. Parameters heading, refers distinctive experimental details
| + | |
- | unique to the usage of parts which should be decided by groups.</span></p>
| + | |
- | <p>Second step for building the standardized template was to get the
| + | |
- | phylogenic information about the parts development process which includes
| + | |
- | the name of the group, designer and contact information, along with
| + | |
- | the comments from the group on the parts they have submitted. Contact
| + | |
- | information is especially important for iGEM as other groups who need
| + | |
- | extra information about the available part can reach to the required
| + | |
- | information. Even though contacting with the designers of the individual
| + | |
- | parts which are available is highly encouraged by iGEM, unavailability
| + | |
- | of contact information points at out the fact that iGEM’s parts registry
| + | |
- | needs strong re-organization in order to serve to the synthetic biology
| + | |
- | community properly.</p>
| + | |
- | <p>Additionally, the “group favorite” and “starRating” fields are also
| + | |
- | important for individual evaluation of the parts, which doesn’t get
| + | |
- | the deserved attention from the iGEM groups. “Group Favorite” defines
| + | |
- | the confidence on the part by the designer group. “StarRating” defines
| + | |
- | the related part in terms of popularity and usage efficiency among the
| + | |
- | groups. According to our observations, most groups are not aware of
| + | |
- | either of the fields or they are used incorrectly or ineffectively.
| + | |
- | For example for a part with a full reporter which is known to be functional
| + | |
- | and gives precise and expected results the StarRating should be at least
| + | |
- | 2 stars, but for most of the parts in 2010 distribution, it is very
| + | |
- | difficult to observe a part whose “StarRating” is above one. For quick
| + | |
- | determination of functionality of the parts these two evaluations are
| + | |
- | important so they have been included in the proposed standardization
| + | |
- | template. But, as they were not properly used up to now for the re-organization
| + | |
- | of the parts information during the development of our software application
| + | |
- | we had to include all parts to our queries regardless of their evaluations
| + | |
- | based on “Group Favorites” and “ StarRatings”</p>
| + | |
- | <p>Second step for building the standardized template was to get the
| + | |
- | phylogenic information about the parts development process which includes
| + | |
- | the name of the group, designer and contact information, along with
| + | |
- | the comments from the group on the parts they have submitted. Contact
| + | |
- | information is especially important for iGEM as other groups who need
| + | |
- | extra information about the available part can reach to the required
| + | |
- | information. Even though contacting with the designers of the individual
| + | |
- | parts which are available is highly encouraged by iGEM, unavailability
| + | |
- | of contact information points at out the fact that iGEM’s parts registry
| + | |
- | needs strong re-organization in order to serve to the synthetic biology
| + | |
- | community properly.</p>
| + | |
- | <p>Additionally, the “group favorite” and “starRating” fields are also
| + | |
- | important for individual evaluation of the parts, which doesn’t get
| + | |
- | the deserved attention from the iGEM groups. “Group Favorite” defines
| + | |
- | the confidence on the part by the designer group. “StarRating” defines
| + | |
- | the related part in terms of popularity and usage efficiency among the
| + | |
- | groups. According to our observations, most groups are not aware of
| + | |
- | either of the fields or they are used incorrectly or ineffectively.
| + | |
- | For example for a part with a full reporter which is known to be functional
| + | |
- | and gives precise and expected results the StarRating should be at least
| + | |
- | 2 stars, but for most of the parts in 2010 distribution, it is very
| + | |
- | difficult to observe a part whose “StarRating” is above one. For quick
| + | |
- | determination of functionality of the parts these two evaluations are
| + | |
- | important so they have been included in the proposed standardization
| + | |
- | template. But, as they were not properly used up to now for the re-organization
| + | |
- | of the parts information during the development of our software application
| + | |
- | we had to include all parts to our queries regardless of their evaluations
| + | |
- | based on “Group Favorites” and “ StarRatings”</p>
| + | |
- | <br>
| + | |
- | <h3>Input and Output Characteristics of Parts</h3>
| + | |
- | <p>=========================================</p>
| + | |
- | <p>Parameters:</p>
| + | |
- | <p>-Input:</p>
| + | |
- | <p>• Promoter:</p>
| + | |
- | <p>• Activity:</p>
| + | |
- | <p>• Inducer:</p>
| + | |
- | <p>• Activator:</p>
| + | |
- | <p>• Repressor:</p>
| + | |
- | <p>• Inhibitor:</p>
| + | |
- | <p>• Promoter2:</p>
| + | |
- | <p>• Activity:</p>
| + | |
- | <p>• Inducer:</p>
| + | |
- | <p>• Activator:</p>
| + | |
- | <p>• Repressor:</p>
| + | |
- | <p>• Inhibitor:</p>
| + | |
- | <p>-Output:</p>
| + | |
- | <p>• Reporter:</p>
| + | |
- | <p>• Reporter2:</p>
| + | |
- | <p>• Regulator:</p>
| + | |
- | <p>• Inducer:</p>
| + | |
- | <p>• Activator:</p>
| + | |
- | <p>• Repressor:</p>
| + | |
- | <p>• Inhibitor:</p>
| + | |
- | <p>• Regulator2:</p>
| + | |
- | <p>• Inducer:</p>
| + | |
- | <p>• Activator:</p>
| + | |
- | <p>• Repressor:</p>
| + | |
- | <p>• Inhibitor:</p>
| + | |
- | <p>-Working Condition:</p>
| + | |
- | <p>=========================================</p>
| + | |
- | <p><span>Table 3: The table above elaborately describes the input relations
| + | |
- | based on promoters and the output products based on the functional genes
| + | |
- | and RNAs which are included within the parts. Working condition simply
| + | |
- | describes any influencing factor or circumstance which is directly related
| + | |
- | with the functional properties of parts.</span></p>
| + | |
- | <p>Third part of our standardization template includes parameters of
| + | |
- | contingent input and output elements. These parameters are classified
| + | |
- | into two groups for simplicity as presented on Table 3. This final part
| + | |
- | of the standardization template includes the upmost important information
| + | |
- | about the Biobricks that are required for the BioGuide Software to run
| + | |
- | its searching algorithm.</p>
| + | |
- | <p>Briefly, BioGuide application is designed to catch the input and
| + | |
- | output relations of individual parts to examine possible Biobricks pathways
| + | |
- | for specific input and output queries. In other words, at pre-experimental
| + | |
- | stage, it helps wet lab biologists to design their unique constructs
| + | |
- | by revealing possible alternative options for pre-determined purposes,
| + | |
- | along with the primary paths. Our ultimate goal is to improve the algorithm
| + | |
- | designed for iGEM 2010 and present a new version of the BioGuide in
| + | |
- | iGEM 2011, which will provide optimum design of constructs for predetermined
| + | |
- | parameters.</p>
| + | |
- | <p>Most of the parts are composed of functional and nonfunctional constructs
| + | |
- | which are formed by atomic parts. And every part should carry the information
| + | |
- | for all of its atomic parts within itself. The “input” heading actually
| + | |
- | stands for promoters. Parts with one or more promoters can be found
| + | |
- | at iGEM’s Parts Registry. Along with the information on which and how
| + | |
- | many promoters a part might have, the activity level of promoters are
| + | |
- | also important to distinguish between a constitutively active promoter
| + | |
- | or a promoter activated by specific physiological processes or states
| + | |
- | etc. This information was crucial for us to dissect in order to run
| + | |
- | our algorithm as it directly affects which inputs can activate the devices
| + | |
- | or the systems.</p>
| + | |
- | <p>Throughout our investigations on the Parts Registry, we found out
| + | |
- | that much of the terminology was being used ambiguously. Although this
| + | |
- | might not be vital for synthetic biologists, it is still endeavoring
| + | |
- | to understand the function of certain regulatory elements which also
| + | |
- | becomes a time consuming task for the researcher. Thus, we recommend
| + | |
- | that the explanations of certain regulatory elements should be redefined
| + | |
- | and fixed especially for synthetic biology for easy communication, sharing
| + | |
- | and searching of information.</p>
| + | |
- | <p>Common misuses of the terminology can guide us to figure out how
| + | |
- | to construct a standard nomenclature for synthetic biology. We claim
| + | |
- | that a standard nomenclature is urgently needed for synthetic biology
| + | |
- | for the following reasons. First of all, synthetic biology is an emerging
| + | |
- | research discipline and an industrial application area which is highly
| + | |
- | promising. Secondly, redefinition of the terminology to build a standard
| + | |
- | nomenclature is needed as some of the terms are prone to be used instead
| + | |
- | of another causing problems related to misuse for the global communication
| + | |
- | about synthetic biology. Lastly, the nomenclature has major importance
| + | |
- | for the construction of a persistent and trustworthy database for synthetic
| + | |
- | biology which serves for the information exhibition and exchange globally.
| + | |
- | For instance, there are obvious misunderstandings about the words which
| + | |
- | are predominantly used for regulation process. We have noticed that,
| + | |
- | the terms “inhibitor” and “repressor” are being used as equivocally
| + | |
- | in the part information pages. Like the lactose inhibitor protein, a
| + | |
- | widely used DNA-binding transcriptional repressor, that have been labeled
| + | |
- | both as “inhibitor” and “repressor” at iGEM’s Parts Registry. Similar
| + | |
- | problems resulting from ambiguous use of terminology also observed with
| + | |
- | regulatory elements. To sum up, we investigated all input elements for
| + | |
- | promoters and classify these elements in terms of their function, affect
| + | |
- | and required input element for them. So, we suggest that terminology
| + | |
- | used for regulation of transcription should be defined clearly on iGEM’s
| + | |
- | website and correct use of terminology should be enforced.</p>
| + | |
- | <p>The second group of parameters was collected under the title “Output”,
| + | |
- | which refers to products of functional genes. In contradiction, the
| + | |
- | term “reporter” has also been described within the same list. Reporters
| + | |
- | are also genes whose products, can be used for screening as an output.
| + | |
- | According to our group, the usage of the term “reporter” for genes is
| + | |
- | unnecessary and cause extra complexity for information distribution
| + | |
- | and gives rise to discrepancies. Instead of using the term “reporter”,
| + | |
- | predefined “gene” description should be used for genes, which can function
| + | |
- | as reporters. The special information which is related with the characteristic
| + | |
- | of that gene should also be presented on part info web page.</p>
| + | |
- | <p>Furthermore, the same terminology “reporter” was used for both atomic
| + | |
- | parts and composite bio-bricks. Also the overall image descriptions
| + | |
- | for these were defined as “reporters”. We want to point out that using
| + | |
- | same nomenclature for both atomic genes and for whole functional constructs
| + | |
- | contributes to the complexity and makes specific explorations difficult
| + | |
- | through the Parts Registry. So, assigning “reporter” for both atomic
| + | |
- | parts and for whole constructs is not a good practice. Instead, we are
| + | |
- | suggesting the usage of other available terminology for the parts listed
| + | |
- | as reporters, which most of the constructs, now known as reporters,
| + | |
- | can be grouped into, such as “protein generators”, “composite parts”
| + | |
- | or “inverters”.</p>
| + | |
- | <p>Devices are whole constructs which are functional and have specific
| + | |
- | and distinct functions. But, as we have observed, unfortunately, the
| + | |
- | term “device” is also being used for parts which are not functional
| + | |
- | and do not have specific functional at all. Moreover, within the classification
| + | |
- | of devices, we argue that some terms are also being used unnecessarily
| + | |
- | and ambiguously. Devices are classified into five types which are protein
| + | |
- | generators, reporters, inverters, receivers and senders, measurement
| + | |
- | devices. For example iGEM defines protein generators as:</p>
| + | |
- | <p>Protein generator = promoter + rbs +gene + terminator</p>
| + | |
- | <p>Though we accept the definition for protein generators, we observed
| + | |
- | that there exist numerous parts which are defined as protein generators
| + | |
- | but actually most of them do not fit to the definition provided above.
| + | |
- | Although some parts are not functional and do not generate proteins
| + | |
- | at all, they are classified as protein generators, which makes searching
| + | |
- | for the parts difficult in the registry. Furthermore, there are also
| + | |
- | numerous parts which are defined as “composite parts” but actually they
| + | |
- | fit to the same definition with protein generators. In order to overcome
| + | |
- | the problem of misuse of device type we have extracted related image
| + | |
- | ID information for the composite parts. Image ID information helped
| + | |
- | us to correctly categorize composite parts depending on its individual
| + | |
- | atomic parts and identify the ones with more than one function, such
| + | |
- | as being both inhibitor and activator. In other words, we used image
| + | |
- | and part IDs in order to merge an input for its outputs.</p>
| + | |
- | <p>Subtitle working conditions, includes all the detailed information
| + | |
- | about the experimental properties of parts, and the details about the
| + | |
- | working process of individual parts and complete devices. Additionally,
| + | |
- | we marked the subtitle “Working Condition” in our standardization template
| + | |
- | as potentially the most important title that helps synthetic biologist
| + | |
- | to better understand the parts functions at iGEM’s part registry database.
| + | |
- | The main problem we have encounter with the subtitle “working condition”
| + | |
- | is within most of the parts the details about working process is not
| + | |
- | enough and not provided regularly. </p>
| + | |
- | <br>
| + | |
- | <h3>Examples of Misuse of Terminology:</h3>
| + | |
- | <h4>For Composite Parts:</h4>
| + | |
- | <p>PartID: BBa_S04055</p>
| + | |
- | <p>PartName: Synthetic lacYZ operon</p>
| + | |
- | <img src="https://static.igem.org/mediawiki/2010/a/ac/Metu-database1.png" />
| + | |
- | <p>This part is functional and responsible for the production of LacY
| + | |
- | and LacZ proteins. This part partially fits the definition for “composite
| + | |
- | part” but actually should be a protein generator as it fits fully to
| + | |
- | the definition of “protein generators”.</p>
| + | |
- | <h4>For Protein Generators:</h4>
| + | |
- | <p>PartID: BBa_J45299</p>
| + | |
- | <p>PartName: PchA & PchB enzyme generator</p>
| + | |
- | <img src="https://static.igem.org/mediawiki/2010/2/2c/Metu-database2.png" />
| + | |
- | <p>The part which is illustrated above actually fits the definition
| + | |
- | for “composite part” but in part registry it is classified as protein
| + | |
- | generator. This part can be functional but it needs a promoter. Even
| + | |
- | though this part is not functional and is not capable of producing protein,
| + | |
- | part registry assigns this product as protein generator. We suggest
| + | |
- | that all parts in the registry, which are composed of more than one
| + | |
- | atomic part and which are not functional on their own but can be functional,
| + | |
- | should be classified as “composite parts”.</p>
| + | |
- | <h4>For Reporters:</h4>
| + | |
- | <p>PartID: BBa_J04451</p>
| + | |
- | <p>PartName: RFP Coding Device with an LVA tag</p>
| + | |
- | <img src="https://static.igem.org/mediawiki/2010/0/0a/Metu-database3.png" />
| + | |
- | <p>This functional part is classified as “Reporter” in the parts registry
| + | |
- | database. It is very clear that this part fits the same description
| + | |
- | as Protein Generator in Biobrick part registry standards. Although,
| + | |
- | this part has specific and known functional role, characterizing this
| + | |
- | part as a reporter is unnecessary and contributes to the level of complexity
| + | |
- | of information provided. Instead, we suggest that this part should be
| + | |
- | classified as “protein generator” and related detailed information about
| + | |
- | the specific function of this part, should be provided in the part information
| + | |
- | page.</p>
| + | |
- | <p>In conclusion, as mentioned above we tried to reorganize and normalize
| + | |
- | the information about parts which is provided in part registry for 2010
| + | |
- | in order to develop our algorithm for the BioGuide application. During
| + | |
- | this process, we encountered some inconsistencies and misuses of the
| + | |
- | terminology being used and also inadequacies about the information provided
| + | |
- | about parts. First of all, we claim that a standard nomenclature should
| + | |
- | be constituted for future use in the field of synthetic biology. Based
| + | |
- | on the information gathered according to new nomenclature a professional
| + | |
- | database should be constructed to address the needs of synthetic biology.
| + | |
- | This will enable easy information exchange and exhibition globally.
| + | |
- | Secondly, although there are enough information about parts exists on
| + | |
- | parts registry database, the information which is provided for parts
| + | |
- | need to be ordered urgently. Furthermore, there should be new experimental
| + | |
- | standards which must be introduced to groups in the part submission
| + | |
- | process for the subtitle “working condition”. These experimental standards
| + | |
- | will be important because the experimental details about parts are not
| + | |
- | satisfying the needs of wet-lab biologists for the design and the construction
| + | |
- | of new Biobricks.</p>
| + | |
- | </div>
| + | |
- | </div>
| + | |
- | </div>
| + | |
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- | </div>
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- | <div id="download5" class="item">
| |
- | <div class="content2">
| |
- | <div class="text">
| |
- | <h2>Contact</h2>
| |
- | </div>
| |
- | </div>
| |
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- | </div>
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- | </div>
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- | <div id="project6" class="item"> | + | |
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| <div class="text"> | | <div class="text"> |
- | <h2>Algorithm</h2> | + | <h2>Attribution and Contributions</h2> |
- | <p>In this section, the step by step functioning of our application,
| + | <p>The BioGUIDE software is a proud product of METU_TURKEY_SOFTWARE group where the students have presented the problem and come up with the solution with minor advising. This project was not a part of an ongoing project in any of the advisors.</p> |
- | along with the encapsulation of the algorithmic concepts of ‘standardization’
| + | <p>The biologist of the team have done the preliminary database standardization by analyzing and collected data from the iGEM Spring 2010 distribution. All the algorithms have been developed by the soon-to-be computer scientist in the group. The Parts registry survey and standardization of the database information on parts have been developed through a colloborotative effort within the group. </p> |
- | of functional iGEM devices are depicted in pictorial forms called flowcharts.
| + | <p>Additionally all the logo, illustrations, animations, video and other visual media and web design has been created by the design team in the group.</p> |
- | Rectangular boxes represent the encapsulation of implementations of
| + | |
- | the computer programs to perform the particular tasks stated in that
| + | |
- | box on the flowcharts. These boxes are sometimes called subprograms,
| + | |
- | objects or packages in Object Oriented software Engineering context.
| + | |
- | The diamonds represent decision branching and they are found between
| + | |
- | two rectangular boxes. The arrows show the direction in which subprograms
| + | |
- | work and communicate. The subprogram at the head of the arrow starts
| + | |
- | executing after the termination of the subprogram at the tail of the
| + | |
- | arrow. Following flowcharts are the high level representations of our
| + | |
- | algorithms developed for the BioGuide software.</p>
| + | |
- | <br>
| + | |
- | <h3>1</h3>
| + | |
- | <img src="https://static.igem.org/mediawiki/2010/9/95/Metu-algorithm1.png" />
| + | |
- | <p><span>Diagram 1. Flowchart of collection, formatting and storage
| + | |
- | of devices data algorithm</span></p>
| + | |
- | <p>Information about the iGEM parts had to be collected in a standardized
| + | |
- | format for our application to function properly. Following data collection
| + | |
- | custom subprograms is needed to parse and forward the data the application’s
| + | |
- | database. In order to achieve this we have designed and implemented
| + | |
- | the algorithm shown in diagram 1. In this algorithm, the first stage
| + | |
- | was to find the list of part IDs of devices which were supplied by iGEM
| + | |
- | in Spring 2010 distribution. This information has been collected from
| + | |
- | two sources 1) plate files in excel format which was available online
| + | |
- | 2) device data provided in xml format, both provided by iGEM. The last
| + | |
- | step in the algorithm was to send the collected partID data to the application’s
| + | |
- | database.</p>
| + | |
- | <br>
| + | |
- | <h3>2.</h3>
| + | |
- | <img src="https://static.igem.org/mediawiki/2010/e/e6/Metu-algorithm2.png" />
| + | |
- | <p><span>Diagram 2. Flowchart for BioGuide execution before and during
| + | |
- | user interaction</span></p>
| + | |
- | <p>Diagram 2 presents the main algorithm, which shows how BioGuide application
| + | |
- | works. In BioGuide the major components are device and Biobrick graphs.
| + | |
- | While the device graph represents input-output (promoter-regulator)
| + | |
- | compatibility combination of iGEM devices, the Biobrick graph represents
| + | |
- | combinations of atomic parts assembled in a device or system. The flowchart
| + | |
- | shows how these graphs are created and embedded into the program, which
| + | |
- | displays both of the graphs to the user when launched. Application presents
| + | |
- | few interactive options to the user when started, which were shown on
| + | |
- | the flowchart under the horizontal, bolded line. As shown on the diagram
| + | |
- | 2, there are four interactive tasks BioGuide can do, where the device
| + | |
- | and Biobricks graphs are utilized. Upon clicking a node on a devices
| + | |
- | or Biobricks graph, that node changes in size and color and the various
| + | |
- | functions shown on the flowchart can be performed then after.</p>
| + | |
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- | <h2>Modeling</h2>
| + | <h2>Development Plans and Project Management</h2> |
- | <h3>Graphical Modeling for Bio-Guide</h3>
| + | <p>The application we are developing can be used by all iGEM members and it’s data is increasing very fast as the iGEM becomes a bigger organization. Moreover, other data resources like NCBI can be imported to this application, hence the user group of application is gets bigger and bigger. In such a situation, extendibility of the application is vital. New data resources and new functions should be added easily. </p> |
- | <h4>Introduction</h4>
| + | <p>Before starting to think about those, first we have to ask to other teams and iGEM headquarters about the BioGuide 1.0 to see the missing points in our idea, and to check our theories. Until developing this idea we were not using professional software approaches. We were planning our weekly tasks and doing those as in the notebook. </p> |
- | <p>Graphical Modeling Theory has been applied to construct four different
| + | <p>After finding a novel software project we have to change our approach. We have to use professional software development approaches to develop such an application to be able to state the requirements exactly and to use a common language between software oriented and biology oriented members in the team.</p> |
- | graphs where relations of atomic parts, devices and systems and the
| + | <p>As we mentioned above, our software can be extended, and new data resources can be imported. The requirements are changing and the problem can be understood better in time. Extreme Programming Approach is developed for such software projects. That is the approach we are going to use in BioGuide2.0</p> |
- | functional combinations that can build new constructs are presented
| + | |
- | for the iGEMs parts registry database. Three graphs are composed of
| + | |
- | iGEM devices and one graph is based on Biobricks. Each graph comprises
| + | |
- | a set of vertices or nodes and a set of edges. In the set of nodes each
| + | |
- | node represents a device, while in the set of edges each edge represents
| + | |
- | the input-output combination of the nodes. These graphs are directed
| + | |
- | graphs as the edges are created according to input-output combination.
| + | |
- | All compatibilities between a regulator and a promoter of an edge is
| + | |
- | created, where the source of this edge is the device with the corresponding
| + | |
- | regulator and target of the edge is the device with the promoter in
| + | |
- | concern.</p>
| + | |
- | <img src="https://static.igem.org/mediawiki/2010/3/3f/Metu-node1.png" />
| + | |
- | <p><span>Fig. 1: A node representing a device</span></p>
| + | |
- | <img src="https://static.igem.org/mediawiki/2010/1/14/Metu-node2.png" />
| + | |
- | <p><span>Fig. 2: Arrow representing an edge between two nodes</span></p>
| + | |
- | <p>The atomic structures used in our graphical model have been represented
| + | |
- | in Figures 1 and 2. A node is represented with a solid circle where
| + | |
- | the label, the part/device ID according to iGEM standards, of the device
| + | |
- | is marked on the foreground. The blue arrows between nodes connect the
| + | |
- | related devices, representing the input-output connectivity. End style
| + | |
- | of the arrow helps us to determine the direction of the node, like in
| + | |
- | Figure 2 where the node labeled BBa_S03520 is the source and BBa_JO9250
| + | |
- | is the target.</p>
| + | |
- | <br>
| + | |
- | <h3>Directivity</h3>
| + | |
- | <p>All the four constructed graphs build for BioGuide are directed graphs.
| + | |
- | So that, for every edge there must be a single source and a target.
| + | |
- | There is no single edge which is bidirectional. In mathematical form
| + | |
- | this can be represented as:</p>
| + | |
- | <p>If an edge e has node v as source and node w as target then the edge
| + | |
- | can be expressed as</p>
| + | |
- | <img src="https://static.igem.org/mediawiki/2010/6/6c/Metu-equation1.png" />
| + | |
- | <p>For a directed graph the combination (v, w) is totally different
| + | |
- | from (w, v). Therefore,</p>
| + | |
- | <img src="https://static.igem.org/mediawiki/2010/a/ac/Metu-equation2.png" />
| + | |
- | <p>The direction of the edges has been represented with the arrows,
| + | |
- | as explained in Figure 2.</p>
| + | |
- | <br>
| + | |
- | <h3>Connectivity</h3>
| + | |
- | <p>The nodes forming their own sub-graphs disconnected from the rest
| + | |
- | of the nodes have been recognized, which showed us the presence of incompatibility
| + | |
- | between few regulators and promoters of the devices. We have observed
| + | |
- | this disconnection in all four of our graphs. The basis of the disconnection
| + | |
- | has been shown in Figure 3, where the two sub-graphs without any edge
| + | |
- | that connects them to the main graph has been presented on the right
| + | |
- | hand side of the diagram. These features classify our graphs as disconnected
| + | |
- | graphs [1].</p>
| + | |
- | <img src="https://static.igem.org/mediawiki/2010/8/8b/Metu-node3.png" />
| + | |
- | <p><span>Fig. 3: A zoomed in screenshot showing two sub-graphs within
| + | |
- | the disconnected graph.</span></p>
| + | |
- | <br>
| + | |
- | <h3>"Semi-Simplicity"</h3>
| + | |
- | <p>A simple graph is a graph in which no more than one edge contains
| + | |
- | the same set of nodes. So, in a simple graph it is not possible to find
| + | |
- | more than one edge with the same source and the same target. Additionally,
| + | |
- | an edge with the same source and target, forming a loop is not allowed.
| + | |
- | But, in synthetic biology it is possible to construct a device consisting
| + | |
- | of devices or bio bricks of the same species or type. Accordingly, our
| + | |
- | graphs are simple graphs with an exception of possible self-containing
| + | |
- | loops, where the edge starts from and ends on the same node. Our graphs
| + | |
- | have an exception of having loops and due to this permitted flexibility
| + | |
- | our graphs are "semi-simple".</p>
| + | |
- | <p>For general information about graphs refer to:</p>
| + | |
- | <p><span><a href="http://en.wikipedia.org/wiki/Graph_(mathematics)">
| + | |
- | [1] http://en.wikipedia.org/wiki/Graph_(mathematics)</a></span></p>
| + | |
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- | <h2>Results</h2>
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- | they will be providing
| |
- | the short description about the part, which synthetic biologists can
| |
- | immediately recognize and utilize during the construction of unique
| |
- | Biobricks. Additionally unique part names will be helpful to identify
| |
- | the devices with more than one Biobrick in their constructs. Assignment
| |
- | of unique and distinct names for parts describing their nature and content
| |
- | will be helpful to researchers for the recognition of and search for
| |
- | the parts.</p>
| |
- | <br>
| |
- | <h3>Headings Selected From Previous Entry Forms for Indication of Standardized
| |
- | Information</h3>
| |
- | <p>=========================================</p>
| |
- | <p>PartID:</p>
| |
- | <p>PartName:</p>
| |
- | <p>Bricks:</p>
| |
- | <p>BrickIDs:</p>
| |
- | <p>ImageIDs:</p>
| |
- | <p>RFC10:</p>
| |
- | <p>RFC21:</p>
| |
- | <p>RFC23:</p>
| |
- | <p>RFC25:</p>
| |
- | <p>=========================================</p>
| |
- | <p><span>Table 1: The table above basically describes and designates
| |
- | qualities of parts which identifies their compositions and demonstrates
| |
- | the status of previously assigned standards. PartID refers to the unique
| |
- | ID number for parts including atomic parts and assemblies. PartName
| |
- | refers to the given unique names to parts. Bricks, refers to the shortcut
| |
- | names which specifies atomic parts. ImageIDs, refers to individual or
| |
- | combination of numbers that are assigned by us. RFCs refers to the states
| |
- | of parts based on RFC standards.</span></p>
| |
- | <p>iGEM both provides individual, atomic parts and pre-combined constructs
| |
- | such as devices and systems. Availability of combined constructs is
| |
- | important to the researchers as combining individual bio-bricks one
| |
- | at a time will be very time consuming. These previously merged constructs,
| |
- | serve as the repository for puzzle and they can be used for different
| |
- | purposes. Up to date the largest and most trustworthy source, for synthetic
| |
- | biology and its components, is iGEM’s parts registry. In 2010, iGEM
| |
- | provided over 1000 parts that have initiated many projects. Having more
| |
- | atomic parts available in the iGEM’s repository, will lead to the design
| |
- | of more complex and robust constructs, and we would have a better chance
| |
- | to design different constructs for unique purposes. Also, for the parts
| |
- | that are already available, extra steps needs to be taken for the quality
| |
- | control and surveillance of these products. The quality control of the
| |
- | information for the parts is essential for the future of iGEM and synthetic
| |
- | biology. Even though we have found pre-determined RFC standards useful
| |
- | and included those to our standardized template, some individual parts
| |
- | still requires re-organization of the information as RFC standards alone
| |
- | for the functionality of parts, does not satisfy the needs for wet lab
| |
- | biologists.</p>
| |
- | <p>Without a question there is an urgent need to build a distinct and
| |
- | specific database well organized with its own standards for synthetic
| |
- | biology; however, development of such a database is not an easy task.</p>
| |
- | <br>
| |
- | <h3>Contact Information of Part Owners and Qualitative Group Comments
| |
- | about Parts</h3>
| |
- | <p>=========================================</p>
| |
- | <p>Designers: Mail:</p>
| |
- | <p>GroupFavorite:</p>
| |
- | <p>StarRating:</p>
| |
- | <p>Parameters:</p>
| |
- | <p>=========================================</p>
| |
- | <p><span>Table 2: The above table simply depicts information about possessors
| |
- | of parts and their contact information and the popularity of the parts
| |
- | for groups. Parameters heading, refers distinctive experimental details
| |
- | unique to the usage of parts which should be decided by groups.</span></p>
| |
- | <p>Second step for building the standardized template was to get the
| |
- | phylogenic information about the parts development process which includes
| |
- | the name of the group, designer and contact information, along with
| |
- | the comments from the group on the parts they have submitted. Contact
| |
- | information is especially important for iGEM as other groups who need
| |
- | extra information about the available part can reach to the required
| |
- | information. Even though contacting with the designers of the individual
| |
- | parts which are available is highly encouraged by iGEM, unavailability
| |
- | of contact information points at out the fact that iGEM’s parts registry
| |
- | needs strong re-organization in order to serve to the synthetic biology
| |
- | community properly.</p>
| |
- | <p>Additionally, the “group favorite” and “starRating” fields are also
| |
- | important for individual evaluation of the parts, which doesn’t get
| |
- | the deserved attention from the iGEM groups. “Group Favorite” defines
| |
- | the confidence on the part by the designer group. “StarRating” defines
| |
- | the related part in terms of popularity and usage efficiency among the
| |
- | groups. According to our observations, most groups are not aware of
| |
- | either of the fields or they are used incorrectly or ineffectively.
| |
- | For example for a part with a full reporter which is known to be functional
| |
- | and gives precise and expected results the StarRating should be at least
| |
- | 2 stars, but for most of the parts in 2010 distribution, it is very
| |
- | difficult to observe a part whose “StarRating” is above one. For quick
| |
- | determination of functionality of the parts these two evaluations are
| |
- | important so they have been included in the proposed standardization
| |
- | template. But, as they were not properly used up to now for the re-organization
| |
- | of the parts information during the development of our software application
| |
- | we had to include all parts to our queries regardless of their evaluations
| |
- | based on “Group Favorites” and “ StarRatings”</p>
| |
- | <p>Second step for building the standardized template was to get the
| |
- | phylogenic information about the parts development process which includes
| |
- | the name of the group, designer and contact information, along with
| |
- | the comments from the group on the parts they have submitted. Contact
| |
- | information is especially important for iGEM as other groups who need
| |
- | extra information about the available part can reach to the required
| |
- | information. Even though contacting with the designers of the individual
| |
- | parts which are available is highly encouraged by iGEM, unavailability
| |
- | of contact information points at out the fact that iGEM’s parts registry
| |
- | needs strong re-organization in order to serve to the synthetic biology
| |
- | community properly.</p>
| |
- | <p>Additionally, the “group favorite” and “starRating” fields are also
| |
- | important for individual evaluation of the parts, which doesn’t get
| |
- | the deserved attention from the iGEM groups. “Group Favorite” defines
| |
- | the confidence on the part by the designer group. “StarRating” defines
| |
- | the related part in terms of popularity and usage efficiency among the
| |
- | groups. According to our observations, most groups are not aware of
| |
- | either of the fields or they are used incorrectly or ineffectively.
| |
- | For example for a part with a full reporter which is known to be functional
| |
- | and gives precise and expected results the StarRating should be at least
| |
- | 2 stars, but for most of the parts in 2010 distribution, it is very
| |
- | difficult to observe a part whose “StarRating” is above one. For quick
| |
- | determination of functionality of the parts these two evaluations are
| |
- | important so they have been included in the proposed standardization
| |
- | template. But, as they were not properly used up to now for the re-organization
| |
- | of the parts information during the development of our software application
| |
- | we had to include all parts to our queries regardless of their evaluations
| |
- | based on “Group Favorites” and “ StarRatings”</p>
| |
- | <br>
| |
- | <h3>Input and Output Characteristics of Parts</h3>
| |
- | <p>=========================================</p>
| |
- | <p>Parameters:</p>
| |
- | <p>-Input:</p>
| |
- | <p>• Promoter:</p>
| |
- | <p>• Activity:</p>
| |
- | <p>• Inducer:</p>
| |
- | <p>• Activator:</p>
| |
- | <p>• Repressor:</p>
| |
- | <p>• Inhibitor:</p>
| |
- | <p>• Promoter2:</p>
| |
- | <p>• Activity:</p>
| |
- | <p>• Inducer:</p>
| |
- | <p>• Activator:</p>
| |
- | <p>• Repressor:</p>
| |
- | <p>• Inhibitor:</p>
| |
- | <p>-Output:</p>
| |
- | <p>• Reporter:</p>
| |
- | <p>• Reporter2:</p>
| |
- | <p>• Regulator:</p>
| |
- | <p>• Inducer:</p>
| |
- | <p>• Activator:</p>
| |
- | <p>• Repressor:</p>
| |
- | <p>• Inhibitor:</p>
| |
- | <p>• Regulator2:</p>
| |
- | <p>• Inducer:</p>
| |
- | <p>• Activator:</p>
| |
- | <p>• Repressor:</p>
| |
- | <p>• Inhibitor:</p>
| |
- | <p>-Working Condition:</p>
| |
- | <p>=========================================</p>
| |
- | <p><span>Table 3: The table above elaborately describes the input relations
| |
- | based on promoters and the output products based on the functional genes
| |
- | and RNAs which are included within the parts. Working condition simply
| |
- | describes any influencing factor or circumstance which is directly related
| |
- | with the functional properties of parts.</span></p>
| |
- | <p>Third part of our standardization template includes parameters of
| |
- | contingent input and output elements. These parameters are classified
| |
- | into two groups for simplicity as presented on Table 3. This final part
| |
- | of the standardization template includes the upmost important information
| |
- | about the Biobricks that are required for the BioGuide Software to run
| |
- | its searching algorithm.</p>
| |
- | <p>Briefly, BioGuide application is designed to catch the input and
| |
- | output relations of individual parts to examine possible Biobricks pathways
| |
- | for specific input and output queries. In other words, at pre-experimental
| |
- | stage, it helps wet lab biologists to design their unique constructs
| |
- | by revealing possible alternative options for pre-determined purposes,
| |
- | along with the primary paths. Our ultimate goal is to improve the algorithm
| |
- | designed for iGEM 2010 and present a new version of the BioGuide in
| |
- | iGEM 2011, which will provide optimum design of constructs for predetermined
| |
- | parameters.</p>
| |
- | <p>Most of the parts are composed of functional and nonfunctional constructs
| |
- | which are formed by atomic parts. And every part should carry the information
| |
- | for all of its atomic parts within itself. The “input” heading actually
| |
- | stands for promoters. Parts with one or more promoters can be found
| |
- | at iGEM’s Parts Registry. Along with the information on which and how
| |
- | many promoters a part might have, the activity level of promoters are
| |
- | also important to distinguish between a constitutively active promoter
| |
- | or a promoter activated by specific physiological processes or states
| |
- | etc. This information was crucial for us to dissect in order to run
| |
- | our algorithm as it directly affects which inputs can activate the devices
| |
- | or the systems.</p>
| |
- | <p>Throughout our investigations on the Parts Registry, we found out
| |
- | that much of the terminology was being used ambiguously. Although this
| |
- | might not be vital for synthetic biologists, it is still endeavoring
| |
- | to understand the function of certain regulatory elements which also
| |
- | becomes a time consuming task for the researcher. Thus, we recommend
| |
- | that the explanations of certain regulatory elements should be redefined
| |
- | and fixed especially for synthetic biology for easy communication, sharing
| |
- | and searching of information.</p>
| |
- | <p>Common misuses of the terminology can guide us to figure out how
| |
- | to construct a standard nomenclature for synthetic biology. We claim
| |
- | that a standard nomenclature is urgently needed for synthetic biology
| |
- | for the following reasons. First of all, synthetic biology is an emerging
| |
- | research discipline and an industrial application area which is highly
| |
- | promising. Secondly, redefinition of the terminology to build a standard
| |
- | nomenclature is needed as some of the terms are prone to be used instead
| |
- | of another causing problems related to misuse for the global communication
| |
- | about synthetic biology. Lastly, the nomenclature has major importance
| |
- | for the construction of a persistent and trustworthy database for synthetic
| |
- | biology which serves for the information exhibition and exchange globally.
| |
- | For instance, there are obvious misunderstandings about the words which
| |
- | are predominantly used for regulation process. We have noticed that,
| |
- | the terms “inhibitor” and “repressor” are being used as equivocally
| |
- | in the part information pages. Like the lactose inhibitor protein, a
| |
- | widely used DNA-binding transcriptional repressor, that have been labeled
| |
- | both as “inhibitor” and “repressor” at iGEM’s Parts Registry. Similar
| |
- | problems resulting from ambiguous use of terminology also observed with
| |
- | regulatory elements. To sum up, we investigated all input elements for
| |
- | promoters and classify these elements in terms of their function, affect
| |
- | and required input element for them. So, we suggest that terminology
| |
- | used for regulation of transcription should be defined clearly on iGEM’s
| |
- | website and correct use of terminology should be enforced.</p>
| |
- | <p>The second group of parameters was collected under the title “Output”,
| |
- | which refers to products of functional genes. In contradiction, the
| |
- | term “reporter” has also been described within the same list. Reporters
| |
- | are also genes whose products, can be used for screening as an output.
| |
- | According to our group, the usage of the term “reporter” for genes is
| |
- | unnecessary and cause extra complexity for information distribution
| |
- | and gives rise to discrepancies. Instead of using the term “reporter”,
| |
- | predefined “gene” description should be used for genes, which can function
| |
- | as reporters. The special information which is related with the characteristic
| |
- | of that gene should also be presented on part info web page.</p>
| |
- | <p>Furthermore, the same terminology “reporter” was used for both atomic
| |
- | parts and composite bio-bricks. Also the overall image descriptions
| |
- | for these were defined as “reporters”. We want to point out that using
| |
- | same nomenclature for both atomic genes and for whole functional constructs
| |
- | contributes to the complexity and makes specific explorations difficult
| |
- | through the Parts Registry. So, assigning “reporter” for both atomic
| |
- | parts and for whole constructs is not a good practice. Instead, we are
| |
- | suggesting the usage of other available terminology for the parts listed
| |
- | as reporters, which most of the constructs, now known as reporters,
| |
- | can be grouped into, such as “protein generators”, “composite parts”
| |
- | or “inverters”.</p>
| |
- | <p>Devices are whole constructs which are functional and have specific
| |
- | and distinct functions. But, as we have observed, unfortunately, the
| |
- | term “device” is also being used for parts which are not functional
| |
- | and do not have specific functional at all. Moreover, within the classification
| |
- | of devices, we argue that some terms are also being used unnecessarily
| |
- | and ambiguously. Devices are classified into five types which are protein
| |
- | generators, reporters, inverters, receivers and senders, measurement
| |
- | devices. For example iGEM defines protein generators as:</p>
| |
- | <p>Protein generator = promoter + rbs +gene + terminator</p>
| |
- | <p>Though we accept the definition for protein generators, we observed
| |
- | that there exist numerous parts which are defined as protein generators
| |
- | but actually most of them do not fit to the definition provided above.
| |
- | Although some parts are not functional and do not generate proteins
| |
- | at all, they are classified as protein generators, which makes searching
| |
- | for the parts difficult in the registry. Furthermore, there are also
| |
- | numerous parts which are defined as “composite parts” but actually they
| |
- | fit to the same definition with protein generators. In order to overcome
| |
- | the problem of misuse of device type we have extracted related image
| |
- | ID information for the composite parts. Image ID information helped
| |
- | us to correctly categorize composite parts depending on its individual
| |
- | atomic parts and identify the ones with more than one function, such
| |
- | as being both inhibitor and activator. In other words, we used image
| |
- | and part IDs in order to merge an input for its outputs.</p>
| |
- | <p>Subtitle working conditions, includes all the detailed information
| |
- | about the experimental properties of parts, and the details about the
| |
- | working process of individual parts and complete devices. Additionally,
| |
- | we marked the subtitle “Working Condition” in our standardization template
| |
- | as potentially the most important title that helps synthetic biologist
| |
- | to better understand the parts functions at iGEM’s part registry database.
| |
- | The main problem we have encounter with the subtitle “working condition”
| |
- | is within most of the parts the details about working process is not
| |
- | enough and not provided regularly. </p>
| |
- | <br>
| |
- | <h3>Examples of Misuse of Terminology:</h3>
| |
- | <h4>For Composite Parts:</h4>
| |
- | <p>PartID: BBa_S04055</p>
| |
- | <p>PartName: Synthetic lacYZ operon</p>
| |
- | <img src="https://static.igem.org/mediawiki/2010/a/ac/Metu-database1.png" />
| |
- | <p>This part is functional and responsible for the production of LacY
| |
- | and LacZ proteins. This part partially fits the definition for “composite
| |
- | part” but actually should be a protein generator as it fits fully to
| |
- | the definition of “protein generators”.</p>
| |
- | <h4>For Protein Generators:</h4>
| |
- | <p>PartID: BBa_J45299</p>
| |
- | <p>PartName: PchA & PchB enzyme generator</p>
| |
- | <img src="https://static.igem.org/mediawiki/2010/2/2c/Metu-database2.png" />
| |
- | <p>The part which is illustrated above actually fits the definition
| |
- | for “composite part” but in part registry it is classified as protein
| |
- | generator. This part can be functional but it needs a promoter. Even
| |
- | though this part is not functional and is not capable of producing protein,
| |
- | part registry assigns this product as protein generator. We suggest
| |
- | that all parts in the registry, which are composed of more than one
| |
- | atomic part and which are not functional on their own but can be functional,
| |
- | should be classified as “composite parts”.</p>
| |
- | <h4>For Reporters:</h4>
| |
- | <p>PartID: BBa_J04451</p>
| |
- | <p>PartName: RFP Coding Device with an LVA tag</p>
| |
- | <img src="https://static.igem.org/mediawiki/2010/0/0a/Metu-database3.png" />
| |
- | <p>This functional part is classified as “Reporter” in the parts registry
| |
- | database. It is very clear that this part fits the same description
| |
- | as Protein Generator in Biobrick part registry standards. Although,
| |
- | this part has specific and known functional role, characterizing this
| |
- | part as a reporter is unnecessary and contributes to the level of complexity
| |
- | of information provided. Instead, we suggest that this part should be
| |
- | classified as “protein generator” and related detailed information about
| |
- | the specific function of this part, should be provided in the part information
| |
- | page.</p>
| |
- | <p>In conclusion, as mentioned above we tried to reorganize and normalize
| |
- | the information about parts which is provided in part registry for 2010
| |
- | in order to develop our algorithm for the BioGuide application. During
| |
- | this process, we encountered some inconsistencies and misuses of the
| |
- | terminology being used and also inadequacies about the information provided
| |
- | about parts. First of all, we claim that a standard nomenclature should
| |
- | be constituted for future use in the field of synthetic biology. Based
| |
- | on the information gathered according to new nomenclature a professional
| |
- | database should be constructed to address the needs of synthetic biology.
| |
- | This will enable easy information exchange and exhibition globally.
| |
- | Secondly, although there are enough information about parts exists on
| |
- | parts registry database, the information which is provided for parts
| |
- | need to be ordered urgently. Furthermore, there should be new experimental
| |
- | standards which must be introduced to groups in the part submission
| |
- | process for the subtitle “working condition”. These experimental standards
| |
- | will be important because the experimental details about parts are not
| |
- | satisfying the needs of wet-lab biologists for the design and the construction
| |
- | of new Biobricks.</p>
| |
- | </div>
| |
- | </div>
| |
| </div> | | </div> |
| <div class="item"> | | <div class="item"> |
- | </div>
| |
- | <div id="download5" class="item">
| |
- | <div class="content2">
| |
- | <div class="text">
| |
- | <h2>Contact</h2>
| |
- | </div>
| |
- | </div>
| |
- | </div>
| |
- | <div class="item">
| |
- | </div>
| |
- | <div class="clear">
| |
- | </div>
| |
- | <!-- 6th row -->
| |
- | <div class="item">
| |
- | </div>
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- | <div class="item">
| |
- | </div>
| |
- | <div class="item">
| |
- | </div>
| |
- | <div class="item">
| |
- | </div>
| |
- | <div id="project6" class="item">
| |
- | <div class="content2">
| |
- | <div class="text">
| |
- | <h2>Algorithm</h2>
| |
- | <p>In this section, the step by step functioning of our application,
| |
- | along with the encapsulation of the algorithmic concepts of ‘standardization’
| |
- | of functional iGEM devices are depicted in pictorial forms called flowcharts.
| |
- | Rectangular boxes represent the encapsulation of implementations of
| |
- | the computer programs to perform the particular tasks stated in that
| |
- | box on the flowcharts. These boxes are sometimes called subprograms,
| |
- | objects or packages in Object Oriented software Engineering context.
| |
- | The diamonds represent decision branching and they are found between
| |
- | two rectangular boxes. The arrows show the direction in which subprograms
| |
- | work and communicate. The subprogram at the head of the arrow starts
| |
- | executing after the termination of the subprogram at the tail of the
| |
- | arrow. Following flowcharts are the high level representations of our
| |
- | algorithms developed for the BioGuide software.</p>
| |
- | <br>
| |
- | <h3>1</h3>
| |
- | <img src="https://static.igem.org/mediawiki/2010/9/95/Metu-algorithm1.png" />
| |
- | <p><span>Diagram 1. Flowchart of collection, formatting and storage
| |
- | of devices data algorithm</span></p>
| |
- | <p>Information about the iGEM parts had to be collected in a standardized
| |
- | format for our application to function properly. Following data collection
| |
- | custom subprograms is needed to parse and forward the data the application’s
| |
- | database. In order to achieve this we have designed and implemented
| |
- | the algorithm shown in diagram 1. In this algorithm, the first stage
| |
- | was to find the list of part IDs of devices which were supplied by iGEM
| |
- | in Spring 2010 distribution. This information has been collected from
| |
- | two sources 1) plate files in excel format which was available online
| |
- | 2) device data provided in xml format, both provided by iGEM. The last
| |
- | step in the algorithm was to send the collected partID data to the application’s
| |
- | database.</p>
| |
- | <br>
| |
- | <h3>2.</h3>
| |
- | <img src="https://static.igem.org/mediawiki/2010/e/e6/Metu-algorithm2.png" />
| |
- | <p><span>Diagram 2. Flowchart for BioGuide execution before and during
| |
- | user interaction</span></p>
| |
- | <p>Diagram 2 presents the main algorithm, which shows how BioGuide application
| |
- | works. In BioGuide the major components are device and Biobrick graphs.
| |
- | While the device graph represents input-output (promoter-regulator)
| |
- | compatibility combination of iGEM devices, the Biobrick graph represents
| |
- | combinations of atomic parts assembled in a device or system. The flowchart
| |
- | shows how these graphs are created and embedded into the program, which
| |
- | displays both of the graphs to the user when launched. Application presents
| |
- | few interactive options to the user when started, which were shown on
| |
- | the flowchart under the horizontal, bolded line. As shown on the diagram
| |
- | 2, there are four interactive tasks BioGuide can do, where the device
| |
- | and Biobricks graphs are utilized. Upon clicking a node on a devices
| |
- | or Biobricks graph, that node changes in size and color and the various
| |
- | functions shown on the flowchart can be performed then after.</p>
| |
- | </div>
| |
- | </div>
| |
- | </div>
| |
- | <div class="item">
| |
- | </div>
| |
- | <div class="item">
| |
- | </div>
| |
- | <div class="item">
| |
- | </div>
| |
- | <div class="clear">
| |
- | </div>
| |
- | <!-- 7th row -->
| |
- | <div class="item">
| |
- | </div>
| |
- | <div class="item">
| |
- | </div>
| |
- | <div class="item">
| |
- | </div>
| |
- | <div class="item">
| |
- | </div>
| |
- | <div id="project7" class="item">
| |
- | <div class="content2">
| |
- | <div class="text">
| |
- | <h2>Modeling</h2>
| |
- | <h3>Graphical Modeling for Bio-Guide</h3>
| |
- | <h4>Introduction</h4>
| |
- | <p>Graphical Modeling Theory has been applied to construct four different
| |
- | graphs where relations of atomic parts, devices and systems and the
| |
- | functional combinations that can build new constructs are presented
| |
- | for the iGEMs parts registry database. Three graphs are composed of
| |
- | iGEM devices and one graph is based on Biobricks. Each graph comprises
| |
- | a set of vertices or nodes and a set of edges. In the set of nodes each
| |
- | node represents a device, while in the set of edges each edge represents
| |
- | the input-output combination of the nodes. These graphs are directed
| |
- | graphs as the edges are created according to input-output combination.
| |
- | All compatibilities between a regulator and a promoter of an edge is
| |
- | created, where the source of this edge is the device with the corresponding
| |
- | regulator and target of the edge is the device with the promoter in
| |
- | concern.</p>
| |
- | <img src="https://static.igem.org/mediawiki/2010/3/3f/Metu-node1.png" />
| |
- | <p><span>Fig. 1: A node representing a device</span></p>
| |
- | <img src="https://static.igem.org/mediawiki/2010/1/14/Metu-node2.png" />
| |
- | <p><span>Fig. 2: Arrow representing an edge between two nodes</span></p>
| |
- | <p>The atomic structures used in our graphical model have been represented
| |
- | in Figures 1 and 2. A node is represented with a solid circle where
| |
- | the label, the part/device ID according to iGEM standards, of the device
| |
- | is marked on the foreground. The blue arrows between nodes connect the
| |
- | related devices, representing the input-output connectivity. End style
| |
- | of the arrow helps us to determine the direction of the node, like in
| |
- | Figure 2 where the node labeled BBa_S03520 is the source and BBa_JO9250
| |
- | is the target.</p>
| |
- | <br>
| |
- | <h3>Directivity</h3>
| |
- | <p>All the four constructed graphs build for BioGuide are directed graphs.
| |
- | So that, for every edge there must be a single source and a target.
| |
- | There is no single edge which is bidirectional. In mathematical form
| |
- | this can be represented as:</p>
| |
- | <p>If an edge e has node v as source and node w as target then the edge
| |
- | can be expressed as</p>
| |
- | <img src="https://static.igem.org/mediawiki/2010/6/6c/Metu-equation1.png" />
| |
- | <p>For a directed graph the combination (v, w) is totally different
| |
- | from (w, v). Therefore,</p>
| |
- | <img src="https://static.igem.org/mediawiki/2010/a/ac/Metu-equation2.png" />
| |
- | <p>The direction of the edges has been represented with the arrows,
| |
- | as explained in Figure 2.</p>
| |
- | <br>
| |
- | <h3>Connectivity</h3>
| |
- | <p>The nodes forming their own sub-graphs disconnected from the rest
| |
- | of the nodes have been recognized, which showed us the presence of incompatibility
| |
- | between few regulators and promoters of the devices. We have observed
| |
- | this disconnection in all four of our graphs. The basis of the disconnection
| |
- | has been shown in Figure 3, where the two sub-graphs without any edge
| |
- | that connects them to the main graph has been presented on the right
| |
- | hand side of the diagram. These features classify our graphs as disconnected
| |
- | graphs [1].</p>
| |
- | <img src="https://static.igem.org/mediawiki/2010/8/8b/Metu-node3.png" />
| |
- | <p><span>Fig. 3: A zoomed in screenshot showing two sub-graphs within
| |
- | the disconnected graph.</span></p>
| |
- | <br>
| |
- | <h3>"Semi-Simplicity"</h3>
| |
- | <p>A simple graph is a graph in which no more than one edge contains
| |
- | the same set of nodes. So, in a simple graph it is not possible to find
| |
- | more than one edge with the same source and the same target. Additionally,
| |
- | an edge with the same source and target, forming a loop is not allowed.
| |
- | But, in synthetic biology it is possible to construct a device consisting
| |
- | of devices or bio bricks of the same species or type. Accordingly, our
| |
- | graphs are simple graphs with an exception of possible self-containing
| |
- | loops, where the edge starts from and ends on the same node. Our graphs
| |
- | have an exception of having loops and due to this permitted flexibility
| |
- | our graphs are "semi-simple".</p>
| |
- | <p>For general information about graphs refer to:</p>
| |
- | <p><span><a href="http://en.wikipedia.org/wiki/Graph_(mathematics)">
| |
- | [1] http://en.wikipedia.org/wiki/Graph_(mathematics)</a></span></p>
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| + | <li><a class="panel" href="#project9">Attribution and Contributions</a></li> |
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