Team:UESTC-Software/Human Practices
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Human Practice
Overview
People engaged in project research tend to focus on their own work and ignore the ideas of the people associated with the project, which makes the project easily divorced from the real environment we are in. Therefore, integrated human practices are a critical part of building a responsible, sustainable, and influential research program. From the beginning, our project is accompanied by the activities of human practice, from problem proposal to research design, to software implementation, and finally feedback verification. It helps us to think critically, allowing us to fully consider the problems that may arise in all aspects of the project.We listen to the views of stakeholders from different perspectives through exchanges, interviews and visits, and establish interdisciplinary exchanges and cooperation to continuously improve our project. Below, we will detail our team's efforts to implement a project-based integrated HP.
Identify the problem
Determine the creativity and importance of the project
There are different ways of looking at the world and different levels of observation. The research on protein design usually starts from the level of amino acids, but the amount of amino acids is so large that the workload of the research process increases dramatically. Therefore, we think whether the design process of proteins can be simplified. Can you splice proteins in big chunks like building blocks?
With this idea in mind, the team members brainstormed for a long time, eventually targeting the domain, a supersecondary structure of proteins. We consulted a large number of literature and found that there were relatively few researches in the domain based on the shape of domain. Once a breakthrough was made, it would bring new ideas for protein research. Therefore, we decided to establish a shape-based domain classification library.
Interview with Professor Zhang Fengli
Professor Zhang Fengli--Professor, School of Computer Science, UESTC
We met with Professor Zhang Fengli to gain knowledge about how to build a professional database. Her valuable insight allowed us to systematically identify functional cores to have a more practical role for the users. We met with her during the early stages of the project, and she advised us to seriously consider the needs of the database's applicable users.
Suggestions：
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1. Identify problems during execution：The problems we the database solve can be clearly presented to users. |
Through Uniprot, CATH, SCOP/SCOP2 and PDB, we have integrated domain division, related functions and probability combination into our own project website, so as to form a complete system of domain shape division, structure, and function; |
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We used an authoritative database recognized by the synthetic biology community. Their strict review system and supporting materials ensure the accuracy of the content on our website; |
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We strived to make CPD3DS a more integrated and user-friendly database that provides synthetic biologists with long-term, stable data updates and search services. |
Interview with Professor Lin Hao
Professor Lin Hao -- Professor, Department of Biotechnology, UESTC and Technology
We met with Professor Lin Hao to talk more about the validation rules of the classification. He suggested that we add verification after finishing the classification and labelling of functions. By comparing the classified results with our reference databases, we verified the similar percentage of domains in the same family/super family library to our classification, thus proving the accuracy of our item classification.
Verification results: Similarity percentage of the family/superfamily library to our classification domain
Interview with Professor Feng Juan
Professor Feng Juan -- Professor of Biotechnology department, University of Electronic Science and Technology of China
In order to further explore the process of protein design and the relationship between protein shape and function, we had the honor to interview Professor Feng Juan, hoping that she can give us some experimental support and suggestions from the perspective of professional research. She told us that if you design a protein from a sequence, including disulfide bonds and so on, which makes it less successful and harder to form the spatial structure that we want. However, this problem can be solved to some extent if proteins are modified in domain units. This gives us great confidence to carry out domain-based research projects.
In response to our proposed link between protein shape and function, she told us that the shape of proteins was very important and closely related to function. Scientists have found that when the chemokines of two proteins have similar shapes and structures, their activity is very similar. This provides a strong support for our research based on 3D shapes.
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1. In what way do you think our project is helpful to your research? |
  Protein design is not easy, and your work can help simplify the process of modification, which is very beneficial for protein modification. |
Laboratory visit & Interview with graduate students
Protein Engineering Laboratory
Protein engineering technology was used to modify the catalytic properties of enzyme catalysts to improve their stability in extreme environments and enhance their application potential
We visited the Lab of Protein Engineering, so as to communicate with researchers about whether it is feasible to conduct research with domain as a unit in actual operation, and hoped to get some suggestions on our project.
We met with senior Zhou. After introducing the idea of our project, he said that there was little research on protein structure and the searching for structure information was limited to the PDB database. However, our method of breaking the traditional amino acid unit to synthesize protein is novel, feasible in theory and of great research significance. But he suggested that we look for examples of successful protein design at the domain level to further validate our ultimate goal.
Which you can find in our
https://2020.igem.org/Team:UESTC-Software/Proof_Of_Concept
We also interviewed graduate student Wang Qian, whose research was to screen and optimize halohydrin dehalogenase by loop substitution. This is consistent with our thinking, except that we chose different levels of research subjects. She replaced a long sequence of the enzyme and used screening criteria to determine the functional impact of the replacement. Her research gave us great confidence.
Demand-based design
Understand the need and Propose solutions
Protein domain visualization project of SJTU
During an online concept exchange meeting with SJTU-Software, we got new project inspiration.
In the free exchange section, they expressed interest in the classification of domains, but proposed data level classification was not convenient for users. Based on this question, we had an in-depth exchange of views, and finally decided to use the SJTU team's virtual lab presentation as a reference. In order to help users understand the 3D shape of the domain, we realized the 3D visualization of the protein domain.
In order to realize the idea of visualization, we also designed the building block Probrick, which is both scientific and interesting and can directly reflect the 3D shape.
Which you can find in our
https://2020.igem.org/Team:UESTC-Software/Education
Online Communication with Maccura
In order to make our project design more relevant to market and application needs, we conducted online interviews with a researcher from Mike Bio-Inc. He made recommendations based on the current market for protein-based drugs and emphasized the effect of the combination of two domains on the properties of synthetic proteins. According to his suggestions, we added the function of analyzing the probability of combination between structural domains on the project website, so as to further meet the market demand and provide better convenience for researchers. 1. Do you think this project provides convenience or assistance to biologists? It is helpful, can provide domain structure reference, design new product. 2. What do you think is the mainstream demand of the protein drug market at present? Protein drugs require low side effects and high specificity. The 3D shape only provides the structural domain of single protein, but the actual process of action is the interaction with other proteins, which needs to be considered in practice. 3. How can our project be closer to your needs? For protein research, the amino acids that make up it are clear. At present, it is very necessary to obtain the 3D structure of proteins and carry out shape comparison and improvement.
1. Do you think this project provides convenience or assistance to biologists?
It is helpful, can provide domain structure reference, design new product.
2. What do you think is the mainstream demand of the protein drug market at present?
Protein drugs require low side effects and high specificity. The 3D shape only provides the structural domain of single protein, but the actual process of action is the interaction with other proteins, which needs to be considered in practice.
3. How can our project be closer to your needs?
For protein research, the amino acids that make up it are clear. At present, it is very necessary to obtain the 3D structure of proteins and carry out shape comparison and improvement.
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Consultation with Law Firm
In view of whether the use of databases contained in CPD3DS will lead to infringement, we consulted lawyer Yan for professional advice. He has rich experience in this field. He advised we need to check carefully on every database to avoid any missing possible regulation on the property of database.
1. In other aspects, we selected and translated the contents of the popular Science section (PDB101) in the International Protein Structure Database (PDB website), and published these contents in the public account. Does this behavior require authorization from PDB101?
According to the provisions of the Copyright Law, new works will be derived from direct translation, within the scope of copyright protection in the Copyright Law. Although the public account is not used for commercial promotion, it is necessary to obtain the permission of PDB101.
2. We used Unity in the project to make creative games about the project. Is there any copyright problem when using the software and model? And what should I pay attention to?
For the paid part of the software, if the identity of students to apply for the educational benefits of the software, get the right to free use, the software does not limit the use and use purpose, there is no copyright problem
Implementation
Find and solve problems in this process
Interview with senior software students
During the implementation of the project, we encountered some problems in the clustering algorithm, so we sought the help of Liu Nan senior and Zhang Zhiyang seniors. They gave us effective Suggestions for further study.
You can find more details in our
https://2020.igem.org/Team:UESTC-Software/Model
CCIC（the 7th Conference of China iGEMer Community）
From August 27th to 31st, we participated in the 7th CCiC.This national summit is independently initiated by Chinese iGEM participating teams and lasts for five days. There are more than 70 participating iGEM teams from more than 60 universities in China. We have received many suggestions from other teams and judges, as well as opportunities to cooperate with other team. During the presentation, judge raised questions about using the K-means algorithm.Thanks to the problem judges raised, we found that there was indeed a lack of proof for using k-means algorithm instead of other algorithms. On this basis, we added comparison content of effects of various clustering methods in the project content to enhance the credibility of using K-means algorithm. After that, we adopted a variety of other clustering algorithms for analysis, but the final classified results were found not to have good clustering effect through manual comparison. Relatively speaking, k-means is the algorithm with the best expression of effect.
2020 Southwestern iGEM Exchange Conference
We took part in the 6th Annual iGEM Exchange Conference hosted by BUCT, with five iGEM teams. The meeting stressed on the inspiration in exchanges of projects among teams. From this conference, We also received suggestions from other teams for project support. They said that a previous protein-design game, Fold it, developed by Baker Lab, University of Washington, was very similar to our project idea and could be used as a reference and even as a game to visualize our project idea of classifying domains based on 3D shapes.
According to their suggestions, we conducted a multi-dimensional investigation on the scientific game, and finally made our game Protein Brick!
Which you can find in our
https://2020.igem.org/Team:UESTC-Software/Education
By dragging and stitching the 3D shape of structural domain, it can help players better understand the structure of proteins and brings a new experience combining science and fun.
In addition, in order to optimize the game, we also conducted a questionnaire collection of players' game experience to learn more about people's feedback on the game.
Interview with Professor Guo Fengbiao
We met with Professor Guo Fengbiao to talk more about the project.
As a bioinformatician, he served as a PI to the iGEM team, and thus, knew the project process very well. He taught us quite a lot about the classification of domains , especially about the relationship. When we mentioned our project, he mentioned that we can look for combinations between different classes, so that we can observe the relationship between shape and function. We've done a few experiments, and if we can get results, it will lead to new research ideas.
Interview with Professor Tang Lixia
Associate Professor Tang Lixia is in charge of 3 projects under research under the National Natural Science Foundation of China, including cell Department, Institute of Biophysics, Chinese Academy of Sciences, Department of Chemistry, University of Groningen, Netherlands.She has published more than 30 papers in academic journals at home and abroad, including 20 papers included by SCI.
For the improvement of the project, we need more professional advice for guidance. Professor Tang Lixia has been involved in research of protein engineering. We mainly consulted her on trends and popularization of synthetic biology. We also received some valuable advice on the design of the project. She suggested that we add virtual screening to reduce the content of the replacement database for biologists and reduce some unnecessary experimental work, which would greatly facilitate experimental science.
According to Professor Tang's suggestion, we tried a lot, but due to the limitation of our professional level, we didn't succeed. We hope that as we continue to learn, we will be able to add this feature to our project.
Maintenance & Feedback
Return visit the Professor Feng Juan
After all the implementation, we got the test version, and return visited the Professor Feng Juan who gave us guidance during the implementation stage. Through the communication with her and her students, we got a new suggestion: one-click update function. Considering the maintainability, sustainability and timeliness of the database, we have added the function to update the database regularly.
Test and Feedback
In addition, we invited many iGEM teams to test our software and received a lot of feedbacks. And then we improved the aesthetic and eliminated some bugs.
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Collaborations with Others
After all the modifications and refinements, we collaborated with Tongji-Software, NWU-CHINA-A, HZAU-China, SCUT_China, BIT and USTC-Software’s projects. Our collaboration not only makes their project more complete, but also makes our project more meaningful.
