Inspiration

Meeting with Professors

We first visited our PI, Teacher Hong Xuan. Teacher Hong Xuan is a professor at our school's School of Life Sciences, who has made great achievements in microbial biosynthesis.

During the conversation, Teacher Hong pointed out that he had been leading several students in research related to designing biosynthetic pathways. However, both teachers and students were troubled by the diverse and complex information on the sources and reliability of plasmids and proteins, as they often had to repeatedly screen based on their own knowledge and experience, which was often time-consuming and exhausting.

However, existing biological information retrieval websites often cannot provide them with satisfactory answers, or the answers are not satisfactory but not convenient to use. Therefore, an idea arises in our minds that we may be able to do something to make the research process easier and also make it easier for newcomers to biological research to get started.

Fig.1 Communication with Prof. Kun Qu

Later, we visited Teacher Qu Kun , who is also a professor at our school's School of Life Sciences, but he mainly focuses on bioinformatics. Because we hope to create a more convenient and integrated bioinformatics website, Teacher Qu Kun's suggestion is very valuable to us.

After a brief understanding of our purpose, Prof.Qu expressed support and encouragement for us to participate in the iGEM competition. Starting from the example of precision medical big data, he explained the important impact of bioinformatics on human life, which strengthened our belief in the intersection of synthetic biology and bioinformatics.

Then, based on our assumption of website functionality, Prof.Qu suggested that we first conduct research on major bioinformatics websites, analyze their advantages and disadvantages, and then weigh these advantages and disadvantages to design the optimal solution. Afterwards, we will contact the laboratory and biological company to see if we can continue with user friendly optimization. Prof.Qu's guidance has made our research ideas and directions clearer.

Education

Science and Technology Week

In late April, we, USTC Software, participated in the Science and Technology Week project organized by the University of Science and Technology of China. We have set up a booth on campus and designed many small experiments related to synthetic biology, so that students can get closer to biological knowledge.

The participants were mostly primary and secondary school students from nearby schools. We help them conduct experiments together and spread some knowledge about synthetic biology. We are very pleased to see them gradually showing interest in synthetic biology, and some even ask us relevant questions.

Fig.2 The students are taking part in our activities

Synthetic Biology Promotion

In early September, we went to the Hefei Science and Technology Museum to promote synthetic biology to more children. With the existing facilities of the Science and Technology Museum, we conducted a science popularization on synthetic biology for the children and attracted more children and parents to come. We have even had the opportunity to communicate with some parents who work in biology or scientific research, which has also taught us how important user friendliness is as an optimization point.

Fig.3 Group photo outside Hefei Science and Technology Museum

In mid September, we went to Baijiaqin Community for science popularization. In this science popularization, we designed a simple synthetic biology experiment - extracting casein from milk. Before the experiment, the captain explained a simple knowledge of synthetic biology to the children, Xiang Yuxiao. Afterwards, with the assistance of other team members, the children successfully extracted tyrosine, and the smiles on their faces let us know that our science popularization through education and entertainment was successful.

Fig.4 Science popularization for Baijiaqin Community

Communication

Discussion with senior schoolmates

Although we have conducted a lot of research, it is unclear what researchers in the field of synthetic biology actually need when using this software. Therefore, we contacted Mr. Cui from the School of Life Sciences. He works in Professor Liu Haiyan's computational biology laboratory and has extensive experience in protein information screening.

We showed him the platform we have built so far and its functional implementation. Mr. Cui is very satisfied with the interactive interface of our platform and believes that it basically meets the needs of users. We also explained to him the algorithm foundation of our project. After listening, Mr. Cui believed that Pross is not a directed evolution website, but a website that does solubility improvement, and the success rate is not high. Therefore, he suggested that we use PSSM scoring matrix, unsupervised learning model, VAE model, and language model to try each one separately to see which one has the best effect. We have been inspired here to change our focus from solely researching existing website content to more trying to combine the models behind it. We appreciate his suggestion.

Participation in CCiC

On May 28th, we attended the CCiC meeting, where we presented our integrated protein design assistance tool after listening to the iGEM team from other schools. We introduced our project from three perspectives: project development background, project architecture, and future development planning.

We planned to develop full process, semi automated design software by calling APIs or open source code from various platforms. Our focus was on integrity, user friendliness, and development efficiency. The project architecture was based on two main models: soluble optimization and phylogenetic tree, referencing more than ten important professional platforms.

After the introduction, we proposed some ideas and questions, while other teams provided their opinions on these questions and asked questions about the specific content of our introduction. During the communication, we learned about the shortcomings in many creative ideas and planning, which made our project architecture more sound.

Fig.5 Introduct our ideas on CCIC

Discussion with senior schoolmates

We communicated with Tongji University through online sharing during the CCIC period. Their CRISPR virus detection direction provides detailed ideas for our website's CRISPR module. At the same time, our website's high integration and user friendliness make their research more convenient, which further increases our confidence and determination in research and development.

We shared our modeling ideas and prediction algorithms, and members of the two teams discussed the specific algorithms and defects used. The Tongji software team has provided us with many valuable suggestions to make our software more stable and robust.

Fig.6 Meet up with Tongji-Software

Visiting Anhui Huaheng Biotechnology Technology Co.,LTD

In late September, we visited Anhui Huaheng Biotechnology Co., Ltd. under the leadership of Professor Hong Yan. Anhui Huaheng Biotechnology Co., Ltd. is committed to the production of Biotechnology products such as alcohols, amino acids, and sugar substitutes. They have invested a lot of effort in the production of alanine, D-panthenol, and arbutin, and have put them into large-scale industrial production.

They were very pleased to know that we were developing a highly integrated and user-friendly bioinformatics platform and hoped it can improve the efficiency of Biotechnology research. They stated that in actual industrial production, biochemical pathways were important factors that need to be considered in production. If an inappropriate biochemical pathway was chosen, not only would the yield be low, but also the efficiency would be low, often leading to high costs. In addition, it was also necessary to consider the shelf life and effectiveness impact caused by product heterogeneity.

We had a lengthy exchange and discussion with their research leader. Of course, we have decided to incorporate more practical considerations into the original software. For example, we will include the efficiency evaluation values of biochemical pathways in the reference data we provide to users.

Fig.7 Visiting Anhui Huaheng Biotechnology Co., Ltd.

Collaboration with Wet Laboratory

To facilitate users in the downstream design of protein sequence optimization, we added a codon optimization algorithm to our platform, referencing DNAworks. However, after testing, we found that the codon optimization program we used only took into account individual codons. Its accuracy and scalability were not strong, resulting in many limitations in practical applications.

By chance, we learned that the USTC experimental team was developing a new codon optimization algorithm. They aimed to use a genetic algorithm, taking the weighted average of ICU and CC within the Kluyveromyces yeast as the fitness measurement standard to screen for the most suitable gene sequences. After several deep discussions, our two teams decided to jointly develop the algorithm and integrate the results into our platform. [Insert picture of our meeting with the wet lab team]

After training and testing with the codon pair distribution of various organisms, we believe that compared to the previously used DNAworks, the new algorithm is more robust and can meet a broader range of design needs.

Of course, we also understand that there are many shortcomings in our current algorithm. We are seeking to collaborate with more teams to enhance the reliability of codon optimization.

Test-run

Website usage experience

After setting up the Prot-DAP platform, we invited students from related fields to test our website and gathered their feedback on its usability.

From a user's perspective, they offered invaluable insights, which encompassed both praise for the Prot-DAP platform and suggestions for improvement.

Praise:

• "The website has bright colors with a modern tech vibe; it responds quickly to user requests and provides comprehensive and rich features, effectively meeting user demands." — Jiaqi Zhang, Sophomore, School of Medicine, Wuhan University
• "The 'Multisequence Alignment' function is very handy; the top navigation bar makes jumping between sections very convenient." — Jiarui Zhao, Sophomore, School of Life Sciences, The Chinese University of Hong Kong
• "Prot-DAP is an outstanding one-stop support design platform. It provides comprehensive and effective data feedback, quickly giving the prerequisites required for experiments. It also comes with a variety of charts sufficient to meet daily research needs." — Mengtong Zhang, School of Life Sciences, University of Science and Technology of China

Suggestions:

• "Although the results displayed are accurate, their presentation is a bit basic. Perhaps consider reformatting for better readability?" — Jiaqi Zhang, Sophomore, School of Medicine, Wuhan University
• "In the Uniprot database, some proteins have the same name but different IDs. When searching by protein name, consider allowing users to choose the final result based on the ID." — Jiarui Zhao, Sophomore, School of Life Sciences, The Chinese University of Hong Kong
• "The speed of transitioning between pages using the slide method is somewhat slow, maybe speed up the animation? Additionally, when copying codon optimization results, it also copies the sequence numbers. This necessitates manual deletion when moving on to primer design. Consider refining the copy mechanism?" — Mengtong Zhang, School of Life Sciences, University of Science and Technology of China

Summary and Outlook:

We are delighted to find that Prot-DAP essentially aligns with our initial vision: an integrated protein design support platform. Nonetheless, through interactions with actual users, we've identified areas where Prot-DAP can further improve, especially in terms of page layout and result presentation.

In the future, we aim to have more people try out Prot-DAP and will proactively address the issues pointed out by users to make Prot-DAP an even better platform.

We welcome other iGEM teams to use Prot-DAP and look forward to your feedback!

Contact us: USTC_Software2023@163.com