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+ | </style> | ||
− | + | <title>PROJECT</title> | |
</head> | </head> | ||
− | <body> | + | |
− | <div style="position:absolute; z-index:0.5; margin: | + | <body> |
− | + | <div style="position:absolute; z-index:0.5; margin:0px 0px 0px 24px;width:100vw; color:white;" id="section"> | |
+ | <nav id="cd-vertical-nav"> | ||
<ul> | <ul> | ||
<li> | <li> | ||
<a href="#section1" data-number="1"> | <a href="#section1" data-number="1"> | ||
<span class="cd-dot"></span> | <span class="cd-dot"></span> | ||
− | <span class="cd-label"> | + | <span class="cd-label">Description</span> |
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− | <span class="cd-label"> | + | <span class="cd-label">Notebook</span> |
+ | </a> | ||
+ | </li> | ||
+ | <li> | ||
+ | <a href="#section4" data-number="4"> | ||
+ | <span class="cd-dot"></span> | ||
+ | <span class="cd-label">Contribution</span> | ||
+ | </a> | ||
+ | </li> | ||
+ | <li> | ||
+ | <a href="#section5" data-number="5"> | ||
+ | <span class="cd-dot"></span> | ||
+ | <span class="cd-label">Validation</span> | ||
+ | </a> | ||
+ | </li> | ||
+ | <li> | ||
+ | <a href="#section6" data-number="6"> | ||
+ | <span class="cd-dot"></span> | ||
+ | <span class="cd-label">Demonstrate</span> | ||
+ | </a> | ||
+ | </li> | ||
+ | <li> | ||
+ | <a href="#section7" data-number="7"> | ||
+ | <span class="cd-dot"></span> | ||
+ | <span class="cd-label">Improve</span> | ||
+ | </a> | ||
+ | </li> | ||
+ | <li> | ||
+ | <a href="#section8" data-number="8"> | ||
+ | <span class="cd-dot"></span> | ||
+ | <span class="cd-label">Collaboration</span> | ||
</a> | </a> | ||
</li> | </li> | ||
</ul> | </ul> | ||
</nav> | </nav> | ||
− | + | <a class="cd-nav-trigger cd-img-replace">Open navigation<span></span></a> | |
− | + | ||
+ | <div class="cd-section"> | ||
+ | <h1 id="EduMainTitle">Project</h1> | ||
+ | <img src="https://static.igem.org/mediawiki/2019/e/e1/T--Tongji_Software--picture-logo2.png" style="width:100vw"></img> | ||
+ | </div> | ||
+ | <section id="section1" class="cd-section"> | ||
+ | <h1 class="title1">Description</h1> | ||
− | + | <h2 class="title2">Overview</h2> | |
− | + | <p class="para"> | |
− | < | + | Our software constructs an optimal synthetic pathway in E. coli or yeast based on the desired product |
− | + | provided by the user. In such a synthetic pathway, we will comprehensively consider the requirements and | |
− | + | provide information about the enzymes needed for each step of the reaction. Finally, along with the | |
− | + | appropriate promoter, the sequences of all the required enzymes are joined together to form a backbone of a | |
− | + | biobrick for the user. At the same time, the relevant research literature , as well as a post-experiment | |
− | + | feedback community, will be provided. | |
− | + | ||
− | + | ||
− | + | ||
− | + | ||
− | + | ||
− | + | ||
− | + | ||
</p> | </p> | ||
− | < | + | |
− | < | + | <h2 class="title2">Why this project —— meet the needs</h2> |
− | + | <p class="para"> | |
− | + | A computational tool for pathway design and reconstruction is needed when synthetic biologists want to | |
− | + | optimize genetic processes within cells, model for yield prediction, make flux balance analysis and generate | |
− | + | value-added products. However, when actually establishing a metabolic pathway, it is a cumbersome problem to | |
− | + | separately purchase different enzymes from different suppliers and transfer them into chassis. We consider | |
− | + | that all the enzymes in a pathway can be constructed in the same plasmid to transfer at one time. And then, | |
− | + | enzymes expression regulation under different conditions will ensure the realization of the pathway. In this | |
− | + | process, synthetic DNA may be an indispensable part. Although the cost of synthetic DNA is not low at | |
− | </ | + | present, it continues to decline. We believe that synthetic DNA will be popular in the future, and by that |
− | + | time, our tools will be more practical.</p> | |
− | + | ||
− | + | <h2 class="title2"> How we start —— inspiration inside iGEM</h2> | |
− | + | <p class="para"> | |
+ | We appreciate three previous iGEM projects that provide part of our inspiration.<br /> | ||
+ | ①Team: Tongji-Software 2018——Their useful tool AlphaAnt shows us the framework to design a pathway.<br /> | ||
+ | ②Team: HokkaidoU_Japan 2012——Their experiments give us confidence to construct multiple enzymes on the same | ||
+ | plasmid.<br /> | ||
+ | ③Team: IIT-Madras 2017——Their statistics on codon preferences give us inspiration for sequence optimization. | ||
</p> | </p> | ||
− | < | + | |
− | <p> | + | <h2 class="title2">What we are doing</h2> |
− | + | <p class="para"> | |
− | + | On the main body, based on the project of Tongji-Software in 2018, we optimize the algorithm by pruning, | |
− | + | and expand the database of the reaction, adding novel reactions. [1] | |
</p> | </p> | ||
− | <p class=" | + | <p class="para"> |
− | + | With reference to the frequency of use of various biological chassis, there are two chassis options | |
− | + | available for users: E. coli and yeast. [2] We will produce different results depending on the strain | |
− | + | selected by the user. | |
− | + | ||
− | + | ||
− | + | ||
</p> | </p> | ||
− | + | <p class="para"> | |
− | <p class=" | + | We select enzymes with higher catalytic efficiency by the nature of the parameters of the enzyme itself. |
− | + | [3] To ensure that the enzyme is expressed normally, we use taxonomic knowledge and sequence alignment | |
− | + | analysis to select strains that are close to the selected chassis as the sequence source for the enzyme. | |
+ | Subsequently, the codons are optimized. In regulating the expression of synthetic sequences, we integrate | ||
+ | the relevant signaling pathways to make the biobrick skeleton in the results more practical. At the same | ||
+ | time, the comprehensive physical and chemical properties of the enzyme are also part of the results, so that | ||
+ | users can apply it in actual experimental operations. | ||
</p> | </p> | ||
− | < | + | <p class="para"> |
− | <p class=" | + | In addition, we consider the association recommendations for the literature on products or enzymes. In this |
− | <p class=" | + | way, users may be able to explore more research directions. |
− | < | + | </p> |
− | <p class=" | + | <p class="para"> |
+ | After all, the results of the design software are ideal. We need to establish a community where synthetic | ||
+ | biologists can exchange ideas and apply feedback after the actual experiment. This community not only | ||
+ | provides users with a reference to the results, but also provides a direction for our developers to improve | ||
+ | the software. | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">Reference</h2> | ||
+ | <p class="para"> | ||
+ | [1] Hadadi N, MohammadiPeyhani H, Miskovic L, Seijo M, Hatzimanikatis V. Enzyme annotation for orphan and | ||
+ | novel reactions using knowledge of substrate reactive sites. Proc Natl Acad Sci U S A. | ||
+ | 2019;116(15):7298–7307.<br /> | ||
+ | [2] Juhyun Kim, Manuel Salvador, Elizabeth Saunders, Jaime González, Claudio Avignone-Rossa, and Jose | ||
+ | Ignacio Jiménez. Properties of alternative microbial hosts used in synthetic biology: towards the design of | ||
+ | a modular chassis. Essays Biochem. 2016 Nov 30; 60(4): 303–313.<br /> | ||
+ | [3] Pablo Carbonell, Jerry Wong, Neil Swainston, Eriko Takano, Nicholas J Turner, Nigel S Scrutton, Douglas | ||
+ | B Kell, Rainer Breitling, Jean-Loup Faulon, Selenzyme: enzyme selection tool for pathway design, | ||
+ | Bioinformatics, Volume 34, Issue 12, 15 June 2018, Pages 2153–2154. | ||
+ | </p> | ||
+ | <a href="#section2" class="cd-scroll-down cd-img-replace">scroll down</a> | ||
+ | </section><!-- cd-section --> | ||
+ | |||
+ | <section id="section2" class="cd-section"> | ||
+ | <h1 class="title1">Design</h1> | ||
+ | <h2 class="title2">Data:</h2> | ||
+ | <p class="para"> | ||
+ | The data of 2018 Tongji-Software team are used and updated, and the physicochemical properties of enzymes | ||
+ | are collated in BRENDA database, including the ratio of Kcat to Km, Km value, optimal pH and optimal | ||
+ | temperature. | ||
+ | |||
+ | </p> | ||
+ | <img src="../img/tmp.png" alt="几个数据库整理出来的数据格式.jpg" id="data-form" /> | ||
+ | |||
+ | <h2 class="title2">Searching Algorithm:</h2> | ||
+ | <img src="../img/tmp.png" alt="算法图示.jpg" id="algorithm-img" /> | ||
+ | <div id="search-algo"> | ||
+ | <p class="para"> | ||
+ | Instead of DFS algorithm which is used in last year, we choose Greedy algorithm. Greedy algorithm is an | ||
+ | algorithmic paradigm that follows the problem-solving heuristic of making the locally optimal choice at | ||
+ | each | ||
+ | stage with the intent of finding a global optimum. In many problems, a greedy strategy does not usually | ||
+ | produce an optimal solution, but nonetheless a greedy heuristic may yield locally optimal solutions that | ||
+ | approximate a globally optimal solution in a reasonable amount of time. And in our software, with | ||
+ | limited | ||
+ | reactions, we made tests and drawn the conclusion that Greedy algorithm can also get a globally optimal | ||
+ | solution with less time. | ||
+ | </p> | ||
</div> | </div> | ||
+ | <h2 class="title2">Ranking criteria:</h2> | ||
+ | <img src="../img/tmp.png" alt="具体图文解释.jpg" id="rank-img" /> | ||
+ | <div id="rank-cri"> | ||
+ | <p class="para"> | ||
+ | When scoring the pathway, we consider thermodynamic feasibility, competition of heterologous reactions, | ||
+ | frequency of reaction and toxicity of compound, which are used in last year’s project. | ||
+ | In the function of Enzyme Selection, we searched for the presence of the required enzyme in the close | ||
+ | source | ||
+ | bacteria of the engineering bacteria according to the affinity of the bacteria. If the same enzyme | ||
+ | exists in | ||
+ | multiple near-source bacteria, we will arrange the sequence according to the physicochemical properties | ||
+ | of | ||
+ | the enzyme, including the ratio of Kcat to Km, Km value, optimal pH and optimal temperature. In order to | ||
+ | measure the adaptability of physical and chemical properties, we build a model. | ||
+ | </p> | ||
+ | </div> | ||
+ | <div id="model-url">model页链接</div> | ||
+ | |||
+ | <h2 class="title2">Literature recommendation:</h2> | ||
+ | <p class="para"> | ||
+ | Considering that users will perform some personalized operations in the practical application of the result | ||
+ | pathway, we provide the relevant literature keywords of compounds in Pubmed required for each step of the | ||
+ | reaction in the form of word clouds. This may inspire users with possible target compounds or a follow-up | ||
+ | research direction. | ||
+ | </p> | ||
+ | <img src="../img/tmp.png" alt="具体原理.jpg" id="theory1" /> | ||
+ | <img src="../img/tmp.png" alt="具体原理.jpg" id="theory2" /> | ||
+ | <img src="../img/tmp.png" alt="具体原理.jpg" id="theory3" /> | ||
+ | |||
+ | <h2 class="title2">Condon optimization:</h2> | ||
+ | <p class="para"> | ||
+ | We searched the codon preference databases of E. coli and yeast from the Internet, and modified the | ||
+ | infrequently used codon with the information in the database to avoid the difficulties caused by translation | ||
+ | and gene expression, and improve the success of expressing foreign genes. | ||
+ | </p> | ||
</section><!-- cd-section --> | </section><!-- cd-section --> | ||
+ | |||
+ | <section id="section3" class="cd-section"> | ||
+ | <h1 class="title1">Notebook</h1> | ||
+ | <h2 class="title2">2019.1 </h2> | ||
+ | <p class="para"> | ||
+ | Determine the igem team personnel Leader: Xu Bo, Shi Huili | ||
+ | Group members: Xing Feiyang, Xu Shudi, Liu Chaoyang, Nie Wei, Zhao Zexin, Piao Xue | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">2019.2-2019.3 </h2> | ||
+ | <p class="para"> | ||
+ | Read literature based on pathways, proteins, disease treatment, enzymes, etc., collect materials that can be | ||
+ | used to prepare the project. In this process, we discussed many directions, and there are many project | ||
+ | themes with very good ideas. However, due to the fact that the research topics are too frontier and the | ||
+ | related theoretical support is small, some topics have been abandoned. | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">2019.3-2019.5 </h2> | ||
+ | <p class="para"> | ||
+ | Hold a group discussion once a week, summarize and exchange the reading literature of each team member, and | ||
+ | determine the final project research direction. | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">2019.4.23 </h2> | ||
+ | <p class="para"> | ||
+ | Establish project research direction: The user provides the required products and related special | ||
+ | requirements. We design the system to find the appropriate path according to the needs. | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">2019.5.18 </h2> | ||
+ | <p class="para"> | ||
+ | Participated in the igem meet-up of Nanjing China Pharmaceutical University in Jiangsu. In this meet-up, we | ||
+ | exchanged ideas with teams from all over the country to learn from each other. In this process, we will | ||
+ | learn from each other and gradually optimize our projects. | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">2019.6.6 </h2> | ||
+ | <p class="para"> | ||
+ | Communicate with Jinweizhi Enterprise in Suzhou, Zhejiang Province, and introduce our project to the | ||
+ | company. The relevant responsible person will answer the questions raised by us from the practical | ||
+ | application point of view and optimize our project from the perspective of the company. We have learned a | ||
+ | lot from this. | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">2019.7-2019.8 </h2> | ||
+ | <p class="para"> | ||
+ | Preparing for a visa to the United States | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">2019.8.19-2019.8.23 </h2> | ||
+ | <p class="para"> | ||
+ | Go to Shenzhen to participate in ccic | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">2019.3.8</h2> | ||
+ | <p class="para"> | ||
+ | Prepare to sign up for igem and registration fee<br /> | ||
+ | Literature reading report:<br /> | ||
+ | |||
+ | Shi Huili: Organizing all cellular pathways<br /> | ||
+ | |||
+ | Xu Bo: Correspond to the original and the protein: the user enters a protein, finds a similar | ||
+ | sequence in the database, and finds the corresponding component, which can express the component | ||
+ | of the protein; <br /> | ||
+ | |||
+ | the user inputs many originals, predicts the structure of the protein; optimizes the | ||
+ | component, searches | ||
+ | Features.Problem: The protein structure is complex and the reverse process is not easy.<br /> | ||
+ | |||
+ | Xing Feiyang: Simulating the interaction between cells<br /> | ||
+ | Find cell pathways linked to disease<br /> | ||
+ | |||
+ | Liu Chaoyang: Procedure for promoter prediction: Given a gene and an upstream | ||
+ | fragment, predict the position | ||
+ | and sequence of the promoter.<br /> | ||
+ | |||
+ | Problem: Only the database about the promoter, there is no database on the | ||
+ | strength of the promoter, the | ||
+ | previous idea may not be feasible.<br /> | ||
+ | |||
+ | Xu Shudi: Screen the strain according to the case characteristics of the | ||
+ | tumor or cancer.<br /> | ||
+ | |||
+ | Nie Yao: Check out the previous year's software project and learn | ||
+ | from it.<br /> | ||
+ | Mention machine learning<br /> | ||
+ | Continue to add new plugins in the follow-up, standardize | ||
+ | experimental reports<br /> | ||
+ | Not only for computers, but also for VR, mobile phones | ||
+ | and other platforms.<br /> | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">2019.3.15</h2> | ||
+ | <p class="para"> | ||
+ | Zhao Zexin: Regarding the award evaluation, you should fill in the safety form, the evaluation criteria of | ||
+ | each award, the precautions about the competition, and the application for other awards.<br /> | ||
+ | |||
+ | Xu Bo: About protein:<br /> | ||
+ | First, the composite protein: on the basis of the original, machine learning<br /> | ||
+ | Second, on protein prediction<br /> | ||
+ | Third, from protein to original design<br /> | ||
+ | Fourth, linked to alpha-ant<br /> | ||
+ | Fifth, template-based model construction<br /> | ||
+ | |||
+ | Shi Huili: Interaction of cell transduction pathways<br /> | ||
+ | Signaling channel mapping software that adds the ability to simulate | ||
+ | experiments<br /> | ||
+ | Prediction of target genes (enrichment analysis) is conducive to the | ||
+ | location of gene knockout<br /> | ||
+ | |||
+ | Liu Zhaoyang: The method of bacterial treatment:<br /> | ||
+ | 1 anchor the antigen to enhance the original immunity of the | ||
+ | cell<br /> | ||
+ | 2 using bacteria as a carrier to carry drugs<br /> | ||
+ | Database of cancer cell surface antigens Antigen<br /> | ||
+ | |||
+ | Xu Shudi: Bacterial therapy, based on the modular | ||
+ | design of the symbiotic bacteria in the human body. | ||
+ | Reduce | ||
+ | error rate.<br /> | ||
+ | |||
+ | Summary: The literature currently being read is | ||
+ | too proactive, and it is difficult to do it. You | ||
+ | need to | ||
+ | refer to the previous software project to | ||
+ | re-determine the direction.<br /> | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">2019.3.22</h2> | ||
+ | <p class="para"> | ||
+ | Xu Bo: Screening of synthetic pathways<br /> | ||
+ | Screening optimal pathways<br /> | ||
+ | |||
+ | Xing Feiyang: Discussion on the Ways of Channel Classification<br /> | ||
+ | Nie Yao: In terms of channel scoring, there is less paper published, and it is necessary to | ||
+ | refer to other fields of expertise.<br /> | ||
+ | Xu Shudi: The role of protein complexes in disease, building a protein network<br /> | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">2019.3.29</h2> | ||
+ | <p class="para"> | ||
+ | Zhao Zexin: Protein and disease related databases and their functions<br /> | ||
+ | Shi Huili: Protein structure prediction, based on neural network, has a high prediction accuracy.<br /> | ||
+ | Xu Shudi: Protein hotspot prediction, the standard for unifying the advantages and disadvantages of | ||
+ | hotspot prediction methods.<br /> | ||
+ | Xing Feiyang: The algorithm idea of the last igem project, the speed can be improved, and the | ||
+ | calculation can be optimized.<br /> | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">2019.4.19</h2> | ||
+ | <p class="para"> | ||
+ | Zhao Zexin: According to the strain selection sequence or feasible<br /> | ||
+ | Liu Chaoyang: text update, keyword summary comprehensive consideration, drawing according to the weight | ||
+ | of words.<br /> | ||
+ | Problem: Large data volumes will report errors, and unwanted prepositions will be listed in | ||
+ | higher-weight words because of the number of occurrences.<br /> | ||
+ | Piao Xue: It is recommended to separate the front and rear ends to determine the function | ||
+ | points. <br /> | ||
+ | About the opening of the server<br /> | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">2019.5.5</h2> | ||
+ | <p class="para"> | ||
+ | (The project research direction has been established: The user provides the required products and related | ||
+ | special requirements, and the system we designed finds the right path according to the needs.)<br /> | ||
+ | Start preparing for a visa<br /> | ||
+ | Database on enzymes: Problem: There is a case where there is a reaction with multiple Km, and a | ||
+ | standard Km | ||
+ | cannot be determined. Lack of universal promoter information<br /> | ||
+ | New message: 1% of the quality of the heterologous protein per stem cell, the relative growth | ||
+ | rate is | ||
+ | reduced by 3%<br /> | ||
+ | Current thinking: Because of the diversity of enzymes required for a reaction, all the | ||
+ | enzymes needed to | ||
+ | synthesize a single pathway for a plasmid provide a template for designing these enzymes. | ||
+ | <br /> | ||
+ | Question: How do I connect a template for each enzyme?<br /> | ||
+ | Solution: Need to further improve the nature of the enzyme<br /> | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">2019.5.10</h2> | ||
+ | <p class="para"> | ||
+ | Design team logo<br /> | ||
+ | Requirements: Reflect the characteristics of the team, with a distinct team characteristics.<br /> | ||
+ | Rearrange project ideas<br /> | ||
+ | The result: from the user's point of view, we think about the use process of the project, the | ||
+ | functions that | ||
+ | we want to achieve and how the functions are closely and smoothly connected. The most important | ||
+ | thing is how | ||
+ | to embody the new design concept of modular design. It brings a simpler and more comfortable | ||
+ | experience to | ||
+ | the user and truly brings convenience to the majority of experimenters. | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">2019.5.24</h2> | ||
+ | <p class="para"> | ||
+ | Discuss our software project name<br /> | ||
+ | About visas: try to sign in advance<br /> | ||
+ | Planning for summer arrangements: Each member is assigned a job.<br /> | ||
+ | About the project:<br /> | ||
+ | Km value has lower concentration requirements<br /> | ||
+ | Question: <br /> | ||
+ | 1. Does the position of the enzyme (distribution in the cell) affect the design of | ||
+ | the pathway?<br /> | ||
+ | 2. The process of achieving the entire pathway may have the effect of toxic | ||
+ | intermediates<br /> | ||
+ | Solution:<br /> | ||
+ | 1 Pick out the steps that produce toxic intermediates and perform in | ||
+ | vitro experiments<br /> | ||
+ | 2 First pick a path that is not toxic, only suggest feasible, and do | ||
+ | not propose how to avoid toxicity (need further discussion)<br /> | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">2019.5.26</h2> | ||
+ | <p class="para"> | ||
+ | Determine the project name: pathlab | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">2019.8.14</h2> | ||
+ | <p class="para"> | ||
+ | Education section: The first post "Programmer iGEMer is online~" is issued on the Tongji iGEM public number, | ||
+ | which introduces the main content of our project pathlab and the problems we want to solve. | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">2019.8.18</h2> | ||
+ | <p class="para"> | ||
+ | All members arrived in Shenzhen | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">2019.8.19</h2> | ||
+ | <p class="para"> | ||
+ | Registration of ccic (Conference of China iGEMer Community) at Shenzhen China Academy of Science and | ||
+ | Technology<br /> | ||
+ | Fly yourself on the signature board<br /> | ||
+ | Introduction to Ccic: ccic is the abbreviation of Conference of China iGEMer Community. It is generally | ||
+ | organized by the school or unit of iGEM team in China, providing a platform for communication and learning | ||
+ | for all iGEMers in China. During the conference, you can not only hear the presentation of each | ||
+ | participating team, but also invite professors who have made achievements in various fields to bring | ||
+ | lectures and answer questions. This year, the ccic held at the China Science and Technology Advanced | ||
+ | Research Institute in Shenzhen is already the sixth. This year, the CCiC conference featured the theme of | ||
+ | “Synbiopunk”. 70 teams from more than 60 colleges and universities across the country presented their | ||
+ | respective entries. They use a multi-disciplinary cross-integration background to combine information | ||
+ | technology and biotechnology, use standard biological modules to construct genetic loops, and establish | ||
+ | effective mathematical models to achieve prediction, manipulation, and measurement of sophisticated complex | ||
+ | artificial biological systems. | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">8.20</h2> | ||
+ | <p class="para"> | ||
+ | Morning :ccic conference opening ceremony | ||
+ | Afternoon: communicate with other teams | ||
+ | RESULTS: With the initial intention of collaboration with China Agricultural University, we can find the | ||
+ | pathway for the synthesis of astaxanthin in China Agricultural University in the pathlab system. In | ||
+ | comparison, our pathway shows an intermediate product that confirms each other. Effectiveness. | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">8.21 </h2> | ||
+ | <p class="para"> | ||
+ | AM: Professor Lei Ruipeng from the Center for Bioethics Research, Huazhong University of Science and | ||
+ | Technology | ||
+ | Our team is presenting <br /> | ||
+ | afternoon: communicate with other participating teams<br /> | ||
+ | |||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">8.22 </h2> | ||
+ | <p class="para"> | ||
+ | Morning Presentation at China Agricultural University<br /> | ||
+ | Night night tour of the window of the world<br /> | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">8.23</h2> | ||
+ | <p class="para"> | ||
+ | Participation in the closing ceremony of the ccic conference<br /> | ||
+ | During the meeting, we gained a lot and found some problems in the project: Since the subject of our project | ||
+ | users is a large number of experimenters, we need to strengthen practice in human practice, reflecting the | ||
+ | operability and convenience of the project. At present, we have reached preliminary cooperation intention | ||
+ | with China Agricultural University. At the same time, the project has been optimized on the algorithm, and | ||
+ | further verification is needed in the accuracy of the algorithm. The user's interactive page design needs to | ||
+ | be improved, and the experimenter needs to be more friendly.<br /> | ||
+ | New idea: The user can insert a message into the tag to provide a user preference function, that is, | ||
+ | according to the tag of the message, when the message is recommended. | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">2019.8.29</h2> | ||
+ | <p class="para"> | ||
+ | Education section: The second post “6th ccic in ShenZhen” was released in the public number tongji iGEM, | ||
+ | which mainly introduces the main activities of the team participating in ccic in Shenzhen and the gains of | ||
+ | the participants. | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">2019.8.31</h2> | ||
+ | <p class="para"> | ||
+ | Regarding the accuracy verification of the ccic algorithm, we have written a relevant program to verify | ||
+ | this.Results: After verification by the program, it can be determined that more than 95% of the data has a | ||
+ | certain degree of optimization compared with the previous algorithm.Sort out the problems with the current | ||
+ | project and the parts that are ready to start:<br /> | ||
+ | 1. The user interface needs to be optimized, and the user interaction needs to be more friendly.<br /> | ||
+ | 2. Start designing the web page<br /> | ||
+ | 3. Preparation of tickets for going abroad and materials for going abroad for group trials | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">2019.9.5</h2> | ||
+ | <p class="para"> | ||
+ | Discuss with the project leader teacher Fei Jian on the current progress of the project.<br /> | ||
+ | Result: In the channel design part, users can be provided with various choices. For example, the user can | ||
+ | input a substance, and the user can carefully select and perform several steps of reaction. According to the | ||
+ | user's choice, the result will display the product desired by the user. | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">2019.9.6 </h2> | ||
+ | <p class="para"> | ||
+ | Education section: The third article, "Efficient Path Finder - Alpha ant", was released in the public number | ||
+ | Tongji iGEM. It mainly introduces the background of the project's predecessor, Alpha ant, the main | ||
+ | algorithm, scoring standards, etc. Better understand our projects. | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">2019.9.7</h2> | ||
+ | <p class="para"> | ||
+ | Prepare the application for the iGEM community, which is mainly to train a group of students who are | ||
+ | interested in the iGEM competition. From the freshman year, they will understand the competition and conduct | ||
+ | the topic selection work. | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">2019.9.10</h2> | ||
+ | <p class="para"> | ||
+ | Received a collaboration invitation from Washington iGEM, mainly about the translation and recording of | ||
+ | audio books. | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">2019.9.19</h2> | ||
+ | <p class="para"> | ||
+ | Confirmation of collaboration with the University of Electronic Science and TechnologyContent: Use data from | ||
+ | the University of Electronic Science and Technology and test it on our software. | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">2019.9.1~2019.9.29</h2> | ||
+ | <p class="para"> | ||
+ | The design of the webpage part mainly includes the search part, the code design of the result part, and the | ||
+ | design and adjustment of the visualization. | ||
+ | </p> | ||
+ | |||
+ | </section><!-- cd-section --> | ||
+ | |||
+ | <section id="section4" class="cd-section"> | ||
+ | <h1 class="title1">contribution</h1> | ||
+ | <p class="para"> | ||
+ | Building a complete pathway requires three steps: searching for a pathway, selecting related enzymes, and | ||
+ | designing parts. These steps are quite difficult for a worker to realize by himself, so we aim at making the | ||
+ | whole process into one software to reduce workers pressure on complicated and boring work. | ||
+ | |||
+ | On this basis, we developed our software called Pathlab, whose core idea is modular design. We made each | ||
+ | step into certain module, and for the users, they can choose to use one module or the combination of any | ||
+ | modules. | ||
+ | |||
+ | In brief, Pathlab makes people who work in synthetic biology have a platform to search a certain pathway | ||
+ | that can be applied. | ||
+ | </p> | ||
+ | <img src="../img/tmp.png" alt="运行截图.jpg" id="work-screenshot" /> | ||
+ | |||
+ | </section><!-- cd-section --> | ||
+ | |||
+ | <section id="section5" class="cd-section"> | ||
+ | <h1 class="title1">Validation</h1> | ||
+ | <p class="para">In order to verify whether pathlab can achieve the expected function, we use software to search | ||
+ | several paths and compare them with the actual paths in the literature.<br /> | ||
+ | |||
+ | EXAMPLE 1<br /> | ||
+ | EXAMPLE 2<br /> | ||
+ | EXAMPLE 3 (中国农业大学的通路,链接至collaboration)<br /> | ||
+ | EXAMPLE 4(四川大学的通路,链接至collaboration)<br /> | ||
+ | </p> | ||
+ | </section><!-- cd-section --> | ||
+ | |||
+ | <section id="section6" class="cd-section"> | ||
+ | <h1 class="title1">Demonstration</h1> | ||
+ | <p></p> | ||
+ | </section><!-- cd-section --> | ||
+ | |||
+ | <section id="section7" class="cd-section"> | ||
+ | <h1 class="title1">Improve</h1> | ||
+ | <p class="para"> | ||
+ | Our software was built on the project of last year's Tongji_Software team. The main improvement is to change | ||
+ | the searching algorithm and add software functions, including the enzyme selection and parts design | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">Searching algorithm</h2> | ||
+ | <p class="para"> | ||
+ | In theory, the greedy algorithm may fail to get a global optimum while improving the speed. However, we use | ||
+ | both DFS algorithm and greedy algorithm to find specific pathways, and then compare the results. We found | ||
+ | that based on the existing database, we made tests to check the accuracy of Greedy in limited reactions | ||
+ | compared with DFS, and the accuracy of two algorithms is similar, but the speed of greedy algorithm is | ||
+ | significantly improved, so we think this is a good improvement. | ||
+ | </p> | ||
+ | <img src="../img/tmp.png" alt="两种算法准确率与速度比较.jpg" id="algo-compare1" /> | ||
+ | <img src="../img/tmp.png" alt="两种算法准确率与速度比较.jpg" id="algo-compare2" /> | ||
+ | |||
+ | <h2 class="title2">Additional functions</h2> | ||
+ | <p class="para"> | ||
+ | In choosing the enzymes needed for each reaction, we establish our own judgment model. At the same time, the | ||
+ | key words related to compounds needed in the pathway were sorted out, and these key words would be presented | ||
+ | as a word cloud. When providing the final result of enzyme selection to the user, the optimized sequence is | ||
+ | provided considering the codon preference for the engineering bacteria. | ||
+ | </p> | ||
+ | <p class="para"> | ||
+ | In parts design, we cleared up the data from iGEM part database, and we made a search engine which enables | ||
+ | users to search parts with their name or a certain function. | ||
+ | </p> | ||
+ | <p class="para"> | ||
+ | These functions can be used as a whole, meanwhile they can be used separately. | ||
+ | </p> | ||
+ | <p class="para"> | ||
+ | What’s more, users can apply for their own account on our website, and can leave a message on the webpage. | ||
+ | We will always pay attention to your message and constantly optimize the Pathlab, and users can also make | ||
+ | comments about optimized enzymes or different parts. Moreover, your message will be seen by other users, and | ||
+ | users can communicate through the message board and user can read others comments about the enzyme or parts | ||
+ | they are going to use. | ||
+ | </p> | ||
+ | </section><!-- cd-section --> | ||
+ | |||
+ | <section id="section8" class="cd-section"> | ||
+ | <h1 class="title1">colleboration</h1> | ||
+ | <p class="para"> | ||
+ | The paths found by our software are based on databases and algorithms, which need to be verified by | ||
+ | practical | ||
+ | experiments. At the same time, the results obtained by our software can provide support for the path design | ||
+ | of the experimental team. | ||
+ | </p> | ||
+ | <p class="para"> | ||
+ | Through CCiC, we had a deep communication with three other experimental teams related to pathways | ||
+ | construction. We know the substrates they own and the products they want to get,then try to design parts | ||
+ | through Pathlab search paths and verify with the pathways they implement. | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">Collaboration 1:Tongji-China</h2> | ||
+ | <p class="para"> | ||
+ | Because we are from the same school, Tongji_China and us have more integrated collaboration from the very | ||
+ | beginning. We had conferences together for several times, and their project is about manufacturing, | ||
+ | meanwhile, ours about pathway search, so we get feedback from them after they used our software, and our | ||
+ | results also inspire them sometimes. | ||
+ | </p> | ||
+ | <p class="para"> | ||
+ | One of their suggestions which had a great influence to us is that we should avoid that some of the result | ||
+ | is that putting some of the groups on a compound and then take it down, which is pretty useless. So we added | ||
+ | codes to avoid this kind of situation take place. And we had searched the pathway they used, but we didn't | ||
+ | get a realistic and practical result, so we realized that the data we used had limitation. | ||
+ | </p> | ||
+ | <p class="para"> | ||
+ | For Tongji_China, they tried to improve the synthesis of indigo, and the method of finding new pathways | ||
+ | could be found through reading literature, experimental attempts through the combination of existing | ||
+ | pathways, or simulated synthesis through software design and retrieval. Therefore, we provided help in | ||
+ | software retrieval. But in the existing database we did not find useful results, because the data in the | ||
+ | synthetic indigo pathways are already published literature or need the experimental materials are too | ||
+ | expensive, not suitable for synthesis, but we found the reaction of the upstream and downstream information | ||
+ | about indigo provide certain reference and support for their experiments, they also try to give us your | ||
+ | attempt to retrieve database does not exist in the reaction, to join the design new reaction, to design | ||
+ | efficient and useful pathways. | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">Collaboration 2:中国农业大学</h2> | ||
+ | <h2 class="title2">Collaboration 3:电子科技大学</h2> | ||
+ | <img src="../img/tmp.png" alt="需要实验结果.jpg" id="needed-result" /> | ||
+ | <img src="../img/tmp.png" alt="软件结果.jpg" id="software-result" /> | ||
+ | <p class="para"> | ||
+ | hhhhhhhh hhhhhhhhhhhhhhh hhhhhhhhh hhhhhhhh hhhhhhh hhhhhhh hhhhhhhhhhhhhhhh hhhhh hhhhhhhhh hh hhhhhhh hhhhhh | ||
+ | hhhhhhhhhhhh hhhhhh hhh hhhhh hhhhhhhhhh hhhhhhhh hhhhhhhhhhhhh hhhhh hh hhhhhhhhhhh hhhhhh h hh hhh hhhhhhhhhhh | ||
+ | hhhhhhhhhhh hhhhhhhhhh hhhhhh h hhhhh hh hhhh hhhhhhhhh hhhhhh hhh h hh hhhhhhhh h hhhhhhhhhhh hhhh h hhh hhhhhhhhhhhhh | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">Collaboration 4:Washington iGEM</h2> | ||
+ | <p class="para"> | ||
+ | Washington iGEM invited us to participate in the manufacturing of their audiobook which is a popular science | ||
+ | of biology, and we mainly do some translation and recording word for them, thus making chinese students can | ||
+ | read and know what biology is. | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">Collaboration 5:SASTRA iGEM</h2> | ||
+ | <p class="para"> | ||
+ | SASTRA iGEM invited us to participate in their manufacturing of their magazine, and our collaboration forms | ||
+ | including but not limited to write articles about synthesis biology and experiment, provide interviews with | ||
+ | professionals, and make the theme of synthesis biology or to shoot related photography. | ||
+ | </p> | ||
+ | |||
+ | <h2 class="title2">Collaboration 6:UCD iGEM</h2> | ||
+ | <p class="para"> | ||
+ | We participated in UCD’s research about the use of mammals in this iGEM competition. | ||
+ | </p> | ||
+ | </section><!-- cd-section --> | ||
+ | |||
+ | <script src="https://2019.igem.org/Template:Tongji_Software/js/jquery_210_min_js?action=raw&ctype=text/javascript"></script> | ||
+ | <script src="https://2019.igem.org/Template:Tongji_Software/js/ProjectMain_js?action=raw&ctype=text/javascript"></script> <!-- Resource jQuery --> | ||
+ | |||
</div> | </div> | ||
</body> | </body> | ||
+ | |||
</html> | </html> |
Latest revision as of 06:44, 11 October 2019
Tongji Software | Pathlab
Project
![](https://static.igem.org/mediawiki/2019/e/e1/T--Tongji_Software--picture-logo2.png)
Description
Overview
Our software constructs an optimal synthetic pathway in E. coli or yeast based on the desired product provided by the user. In such a synthetic pathway, we will comprehensively consider the requirements and provide information about the enzymes needed for each step of the reaction. Finally, along with the appropriate promoter, the sequences of all the required enzymes are joined together to form a backbone of a biobrick for the user. At the same time, the relevant research literature , as well as a post-experiment feedback community, will be provided.
Why this project —— meet the needs
A computational tool for pathway design and reconstruction is needed when synthetic biologists want to optimize genetic processes within cells, model for yield prediction, make flux balance analysis and generate value-added products. However, when actually establishing a metabolic pathway, it is a cumbersome problem to separately purchase different enzymes from different suppliers and transfer them into chassis. We consider that all the enzymes in a pathway can be constructed in the same plasmid to transfer at one time. And then, enzymes expression regulation under different conditions will ensure the realization of the pathway. In this process, synthetic DNA may be an indispensable part. Although the cost of synthetic DNA is not low at present, it continues to decline. We believe that synthetic DNA will be popular in the future, and by that time, our tools will be more practical.
How we start —— inspiration inside iGEM
We appreciate three previous iGEM projects that provide part of our inspiration.
①Team: Tongji-Software 2018——Their useful tool AlphaAnt shows us the framework to design a pathway.
②Team: HokkaidoU_Japan 2012——Their experiments give us confidence to construct multiple enzymes on the same
plasmid.
③Team: IIT-Madras 2017——Their statistics on codon preferences give us inspiration for sequence optimization.
What we are doing
On the main body, based on the project of Tongji-Software in 2018, we optimize the algorithm by pruning, and expand the database of the reaction, adding novel reactions. [1]
With reference to the frequency of use of various biological chassis, there are two chassis options available for users: E. coli and yeast. [2] We will produce different results depending on the strain selected by the user.
We select enzymes with higher catalytic efficiency by the nature of the parameters of the enzyme itself. [3] To ensure that the enzyme is expressed normally, we use taxonomic knowledge and sequence alignment analysis to select strains that are close to the selected chassis as the sequence source for the enzyme. Subsequently, the codons are optimized. In regulating the expression of synthetic sequences, we integrate the relevant signaling pathways to make the biobrick skeleton in the results more practical. At the same time, the comprehensive physical and chemical properties of the enzyme are also part of the results, so that users can apply it in actual experimental operations.
In addition, we consider the association recommendations for the literature on products or enzymes. In this way, users may be able to explore more research directions.
After all, the results of the design software are ideal. We need to establish a community where synthetic biologists can exchange ideas and apply feedback after the actual experiment. This community not only provides users with a reference to the results, but also provides a direction for our developers to improve the software.
Reference
[1] Hadadi N, MohammadiPeyhani H, Miskovic L, Seijo M, Hatzimanikatis V. Enzyme annotation for orphan and
novel reactions using knowledge of substrate reactive sites. Proc Natl Acad Sci U S A.
2019;116(15):7298–7307.
[2] Juhyun Kim, Manuel Salvador, Elizabeth Saunders, Jaime González, Claudio Avignone-Rossa, and Jose
Ignacio Jiménez. Properties of alternative microbial hosts used in synthetic biology: towards the design of
a modular chassis. Essays Biochem. 2016 Nov 30; 60(4): 303–313.
[3] Pablo Carbonell, Jerry Wong, Neil Swainston, Eriko Takano, Nicholas J Turner, Nigel S Scrutton, Douglas
B Kell, Rainer Breitling, Jean-Loup Faulon, Selenzyme: enzyme selection tool for pathway design,
Bioinformatics, Volume 34, Issue 12, 15 June 2018, Pages 2153–2154.
Design
Data:
The data of 2018 Tongji-Software team are used and updated, and the physicochemical properties of enzymes are collated in BRENDA database, including the ratio of Kcat to Km, Km value, optimal pH and optimal temperature.
![几个数据库整理出来的数据格式.jpg](../img/tmp.png)
Searching Algorithm:
![算法图示.jpg](../img/tmp.png)
Instead of DFS algorithm which is used in last year, we choose Greedy algorithm. Greedy algorithm is an algorithmic paradigm that follows the problem-solving heuristic of making the locally optimal choice at each stage with the intent of finding a global optimum. In many problems, a greedy strategy does not usually produce an optimal solution, but nonetheless a greedy heuristic may yield locally optimal solutions that approximate a globally optimal solution in a reasonable amount of time. And in our software, with limited reactions, we made tests and drawn the conclusion that Greedy algorithm can also get a globally optimal solution with less time.
Ranking criteria:
![具体图文解释.jpg](../img/tmp.png)
When scoring the pathway, we consider thermodynamic feasibility, competition of heterologous reactions, frequency of reaction and toxicity of compound, which are used in last year’s project. In the function of Enzyme Selection, we searched for the presence of the required enzyme in the close source bacteria of the engineering bacteria according to the affinity of the bacteria. If the same enzyme exists in multiple near-source bacteria, we will arrange the sequence according to the physicochemical properties of the enzyme, including the ratio of Kcat to Km, Km value, optimal pH and optimal temperature. In order to measure the adaptability of physical and chemical properties, we build a model.
Literature recommendation:
Considering that users will perform some personalized operations in the practical application of the result pathway, we provide the relevant literature keywords of compounds in Pubmed required for each step of the reaction in the form of word clouds. This may inspire users with possible target compounds or a follow-up research direction.
![具体原理.jpg](../img/tmp.png)
![具体原理.jpg](../img/tmp.png)
![具体原理.jpg](../img/tmp.png)
Condon optimization:
We searched the codon preference databases of E. coli and yeast from the Internet, and modified the infrequently used codon with the information in the database to avoid the difficulties caused by translation and gene expression, and improve the success of expressing foreign genes.
Notebook
2019.1
Determine the igem team personnel Leader: Xu Bo, Shi Huili Group members: Xing Feiyang, Xu Shudi, Liu Chaoyang, Nie Wei, Zhao Zexin, Piao Xue
2019.2-2019.3
Read literature based on pathways, proteins, disease treatment, enzymes, etc., collect materials that can be used to prepare the project. In this process, we discussed many directions, and there are many project themes with very good ideas. However, due to the fact that the research topics are too frontier and the related theoretical support is small, some topics have been abandoned.
2019.3-2019.5
Hold a group discussion once a week, summarize and exchange the reading literature of each team member, and determine the final project research direction.
2019.4.23
Establish project research direction: The user provides the required products and related special requirements. We design the system to find the appropriate path according to the needs.
2019.5.18
Participated in the igem meet-up of Nanjing China Pharmaceutical University in Jiangsu. In this meet-up, we exchanged ideas with teams from all over the country to learn from each other. In this process, we will learn from each other and gradually optimize our projects.
2019.6.6
Communicate with Jinweizhi Enterprise in Suzhou, Zhejiang Province, and introduce our project to the company. The relevant responsible person will answer the questions raised by us from the practical application point of view and optimize our project from the perspective of the company. We have learned a lot from this.
2019.7-2019.8
Preparing for a visa to the United States
2019.8.19-2019.8.23
Go to Shenzhen to participate in ccic
2019.3.8
Prepare to sign up for igem and registration fee
Literature reading report:
Shi Huili: Organizing all cellular pathways
Xu Bo: Correspond to the original and the protein: the user enters a protein, finds a similar
sequence in the database, and finds the corresponding component, which can express the component
of the protein;
the user inputs many originals, predicts the structure of the protein; optimizes the
component, searches
Features.Problem: The protein structure is complex and the reverse process is not easy.
Xing Feiyang: Simulating the interaction between cells
Find cell pathways linked to disease
Liu Chaoyang: Procedure for promoter prediction: Given a gene and an upstream
fragment, predict the position
and sequence of the promoter.
Problem: Only the database about the promoter, there is no database on the
strength of the promoter, the
previous idea may not be feasible.
Xu Shudi: Screen the strain according to the case characteristics of the
tumor or cancer.
Nie Yao: Check out the previous year's software project and learn
from it.
Mention machine learning
Continue to add new plugins in the follow-up, standardize
experimental reports
Not only for computers, but also for VR, mobile phones
and other platforms.
2019.3.15
Zhao Zexin: Regarding the award evaluation, you should fill in the safety form, the evaluation criteria of
each award, the precautions about the competition, and the application for other awards.
Xu Bo: About protein:
First, the composite protein: on the basis of the original, machine learning
Second, on protein prediction
Third, from protein to original design
Fourth, linked to alpha-ant
Fifth, template-based model construction
Shi Huili: Interaction of cell transduction pathways
Signaling channel mapping software that adds the ability to simulate
experiments
Prediction of target genes (enrichment analysis) is conducive to the
location of gene knockout
Liu Zhaoyang: The method of bacterial treatment:
1 anchor the antigen to enhance the original immunity of the
cell
2 using bacteria as a carrier to carry drugs
Database of cancer cell surface antigens Antigen
Xu Shudi: Bacterial therapy, based on the modular
design of the symbiotic bacteria in the human body.
Reduce
error rate.
Summary: The literature currently being read is
too proactive, and it is difficult to do it. You
need to
refer to the previous software project to
re-determine the direction.
2019.3.22
Xu Bo: Screening of synthetic pathways
Screening optimal pathways
Xing Feiyang: Discussion on the Ways of Channel Classification
Nie Yao: In terms of channel scoring, there is less paper published, and it is necessary to
refer to other fields of expertise.
Xu Shudi: The role of protein complexes in disease, building a protein network
2019.3.29
Zhao Zexin: Protein and disease related databases and their functions
Shi Huili: Protein structure prediction, based on neural network, has a high prediction accuracy.
Xu Shudi: Protein hotspot prediction, the standard for unifying the advantages and disadvantages of
hotspot prediction methods.
Xing Feiyang: The algorithm idea of the last igem project, the speed can be improved, and the
calculation can be optimized.
2019.4.19
Zhao Zexin: According to the strain selection sequence or feasible
Liu Chaoyang: text update, keyword summary comprehensive consideration, drawing according to the weight
of words.
Problem: Large data volumes will report errors, and unwanted prepositions will be listed in
higher-weight words because of the number of occurrences.
Piao Xue: It is recommended to separate the front and rear ends to determine the function
points.
About the opening of the server
2019.5.5
(The project research direction has been established: The user provides the required products and related
special requirements, and the system we designed finds the right path according to the needs.)
Start preparing for a visa
Database on enzymes: Problem: There is a case where there is a reaction with multiple Km, and a
standard Km
cannot be determined. Lack of universal promoter information
New message: 1% of the quality of the heterologous protein per stem cell, the relative growth
rate is
reduced by 3%
Current thinking: Because of the diversity of enzymes required for a reaction, all the
enzymes needed to
synthesize a single pathway for a plasmid provide a template for designing these enzymes.
Question: How do I connect a template for each enzyme?
Solution: Need to further improve the nature of the enzyme
2019.5.10
Design team logo
Requirements: Reflect the characteristics of the team, with a distinct team characteristics.
Rearrange project ideas
The result: from the user's point of view, we think about the use process of the project, the
functions that
we want to achieve and how the functions are closely and smoothly connected. The most important
thing is how
to embody the new design concept of modular design. It brings a simpler and more comfortable
experience to
the user and truly brings convenience to the majority of experimenters.
2019.5.24
Discuss our software project name
About visas: try to sign in advance
Planning for summer arrangements: Each member is assigned a job.
About the project:
Km value has lower concentration requirements
Question:
1. Does the position of the enzyme (distribution in the cell) affect the design of
the pathway?
2. The process of achieving the entire pathway may have the effect of toxic
intermediates
Solution:
1 Pick out the steps that produce toxic intermediates and perform in
vitro experiments
2 First pick a path that is not toxic, only suggest feasible, and do
not propose how to avoid toxicity (need further discussion)
2019.5.26
Determine the project name: pathlab
2019.8.14
Education section: The first post "Programmer iGEMer is online~" is issued on the Tongji iGEM public number, which introduces the main content of our project pathlab and the problems we want to solve.
2019.8.18
All members arrived in Shenzhen
2019.8.19
Registration of ccic (Conference of China iGEMer Community) at Shenzhen China Academy of Science and
Technology
Fly yourself on the signature board
Introduction to Ccic: ccic is the abbreviation of Conference of China iGEMer Community. It is generally
organized by the school or unit of iGEM team in China, providing a platform for communication and learning
for all iGEMers in China. During the conference, you can not only hear the presentation of each
participating team, but also invite professors who have made achievements in various fields to bring
lectures and answer questions. This year, the ccic held at the China Science and Technology Advanced
Research Institute in Shenzhen is already the sixth. This year, the CCiC conference featured the theme of
“Synbiopunk”. 70 teams from more than 60 colleges and universities across the country presented their
respective entries. They use a multi-disciplinary cross-integration background to combine information
technology and biotechnology, use standard biological modules to construct genetic loops, and establish
effective mathematical models to achieve prediction, manipulation, and measurement of sophisticated complex
artificial biological systems.
8.20
Morning :ccic conference opening ceremony Afternoon: communicate with other teams RESULTS: With the initial intention of collaboration with China Agricultural University, we can find the pathway for the synthesis of astaxanthin in China Agricultural University in the pathlab system. In comparison, our pathway shows an intermediate product that confirms each other. Effectiveness.
8.21
AM: Professor Lei Ruipeng from the Center for Bioethics Research, Huazhong University of Science and
Technology
Our team is presenting
afternoon: communicate with other participating teams
8.22
Morning Presentation at China Agricultural University
Night night tour of the window of the world
8.23
Participation in the closing ceremony of the ccic conference
During the meeting, we gained a lot and found some problems in the project: Since the subject of our project
users is a large number of experimenters, we need to strengthen practice in human practice, reflecting the
operability and convenience of the project. At present, we have reached preliminary cooperation intention
with China Agricultural University. At the same time, the project has been optimized on the algorithm, and
further verification is needed in the accuracy of the algorithm. The user's interactive page design needs to
be improved, and the experimenter needs to be more friendly.
New idea: The user can insert a message into the tag to provide a user preference function, that is,
according to the tag of the message, when the message is recommended.
2019.8.29
Education section: The second post “6th ccic in ShenZhen” was released in the public number tongji iGEM, which mainly introduces the main activities of the team participating in ccic in Shenzhen and the gains of the participants.
2019.8.31
Regarding the accuracy verification of the ccic algorithm, we have written a relevant program to verify
this.Results: After verification by the program, it can be determined that more than 95% of the data has a
certain degree of optimization compared with the previous algorithm.Sort out the problems with the current
project and the parts that are ready to start:
1. The user interface needs to be optimized, and the user interaction needs to be more friendly.
2. Start designing the web page
3. Preparation of tickets for going abroad and materials for going abroad for group trials
2019.9.5
Discuss with the project leader teacher Fei Jian on the current progress of the project.
Result: In the channel design part, users can be provided with various choices. For example, the user can
input a substance, and the user can carefully select and perform several steps of reaction. According to the
user's choice, the result will display the product desired by the user.
2019.9.6
Education section: The third article, "Efficient Path Finder - Alpha ant", was released in the public number Tongji iGEM. It mainly introduces the background of the project's predecessor, Alpha ant, the main algorithm, scoring standards, etc. Better understand our projects.
2019.9.7
Prepare the application for the iGEM community, which is mainly to train a group of students who are interested in the iGEM competition. From the freshman year, they will understand the competition and conduct the topic selection work.
2019.9.10
Received a collaboration invitation from Washington iGEM, mainly about the translation and recording of audio books.
2019.9.19
Confirmation of collaboration with the University of Electronic Science and TechnologyContent: Use data from the University of Electronic Science and Technology and test it on our software.
2019.9.1~2019.9.29
The design of the webpage part mainly includes the search part, the code design of the result part, and the design and adjustment of the visualization.
contribution
Building a complete pathway requires three steps: searching for a pathway, selecting related enzymes, and designing parts. These steps are quite difficult for a worker to realize by himself, so we aim at making the whole process into one software to reduce workers pressure on complicated and boring work. On this basis, we developed our software called Pathlab, whose core idea is modular design. We made each step into certain module, and for the users, they can choose to use one module or the combination of any modules. In brief, Pathlab makes people who work in synthetic biology have a platform to search a certain pathway that can be applied.
![运行截图.jpg](../img/tmp.png)
Validation
In order to verify whether pathlab can achieve the expected function, we use software to search
several paths and compare them with the actual paths in the literature.
EXAMPLE 1
EXAMPLE 2
EXAMPLE 3 (中国农业大学的通路,链接至collaboration)
EXAMPLE 4(四川大学的通路,链接至collaboration)
Demonstration
Improve
Our software was built on the project of last year's Tongji_Software team. The main improvement is to change the searching algorithm and add software functions, including the enzyme selection and parts design
Searching algorithm
In theory, the greedy algorithm may fail to get a global optimum while improving the speed. However, we use both DFS algorithm and greedy algorithm to find specific pathways, and then compare the results. We found that based on the existing database, we made tests to check the accuracy of Greedy in limited reactions compared with DFS, and the accuracy of two algorithms is similar, but the speed of greedy algorithm is significantly improved, so we think this is a good improvement.
![两种算法准确率与速度比较.jpg](../img/tmp.png)
![两种算法准确率与速度比较.jpg](../img/tmp.png)
Additional functions
In choosing the enzymes needed for each reaction, we establish our own judgment model. At the same time, the key words related to compounds needed in the pathway were sorted out, and these key words would be presented as a word cloud. When providing the final result of enzyme selection to the user, the optimized sequence is provided considering the codon preference for the engineering bacteria.
In parts design, we cleared up the data from iGEM part database, and we made a search engine which enables users to search parts with their name or a certain function.
These functions can be used as a whole, meanwhile they can be used separately.
What’s more, users can apply for their own account on our website, and can leave a message on the webpage. We will always pay attention to your message and constantly optimize the Pathlab, and users can also make comments about optimized enzymes or different parts. Moreover, your message will be seen by other users, and users can communicate through the message board and user can read others comments about the enzyme or parts they are going to use.
colleboration
The paths found by our software are based on databases and algorithms, which need to be verified by practical experiments. At the same time, the results obtained by our software can provide support for the path design of the experimental team.
Through CCiC, we had a deep communication with three other experimental teams related to pathways construction. We know the substrates they own and the products they want to get,then try to design parts through Pathlab search paths and verify with the pathways they implement.
Collaboration 1:Tongji-China
Because we are from the same school, Tongji_China and us have more integrated collaboration from the very beginning. We had conferences together for several times, and their project is about manufacturing, meanwhile, ours about pathway search, so we get feedback from them after they used our software, and our results also inspire them sometimes.
One of their suggestions which had a great influence to us is that we should avoid that some of the result is that putting some of the groups on a compound and then take it down, which is pretty useless. So we added codes to avoid this kind of situation take place. And we had searched the pathway they used, but we didn't get a realistic and practical result, so we realized that the data we used had limitation.
For Tongji_China, they tried to improve the synthesis of indigo, and the method of finding new pathways could be found through reading literature, experimental attempts through the combination of existing pathways, or simulated synthesis through software design and retrieval. Therefore, we provided help in software retrieval. But in the existing database we did not find useful results, because the data in the synthetic indigo pathways are already published literature or need the experimental materials are too expensive, not suitable for synthesis, but we found the reaction of the upstream and downstream information about indigo provide certain reference and support for their experiments, they also try to give us your attempt to retrieve database does not exist in the reaction, to join the design new reaction, to design efficient and useful pathways.
Collaboration 2:中国农业大学
Collaboration 3:电子科技大学
![需要实验结果.jpg](../img/tmp.png)
![软件结果.jpg](../img/tmp.png)
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Collaboration 4:Washington iGEM
Washington iGEM invited us to participate in the manufacturing of their audiobook which is a popular science of biology, and we mainly do some translation and recording word for them, thus making chinese students can read and know what biology is.
Collaboration 5:SASTRA iGEM
SASTRA iGEM invited us to participate in their manufacturing of their magazine, and our collaboration forms including but not limited to write articles about synthesis biology and experiment, provide interviews with professionals, and make the theme of synthesis biology or to shoot related photography.
Collaboration 6:UCD iGEM
We participated in UCD’s research about the use of mammals in this iGEM competition.