Therapeutic Target Database (TTD) Review

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Purpose

The purpose of this assignment is to explore and evaluate the Therapeutic Target Database (TTD), which provides information on therapeutic protein and nucleic acid targets and their targeted diseases, pathway information, and the drugs directed at them. Analyzing the database will allow us to judge its usefulness as a resource for research and development of targeted therapeutics.

Database Evaluation

General information about the database

  1. What is the name of the database?
  2. What type (or types) of database is it?
    1. What biological information (type of data) does it contain? (sequence, structure, model organism, or specialty [what?])
      • The Therapeutic Target Database is a metabolic and signaling pathways database. More specifically, the database is focused on therapeutic protein and nucleic acid targets, targeted disease, pathway information, and drugs directed at each target. The type of information included in the database is outlined on this page.
    2. What type of data source does it have?
      • The information in the database is secondary, and is fully referenced.
      • The database is organized into categories. You can do an advanced customized search, a biomarker search, a pathway search, a coronavirus search, a target sequence similarity search, or a drug structure similarity search. There are also categories to explore target groups, drug groups, patient data, and models.
      • The data appears to be human curated.
  3. What individual or organization maintains the database?
  4. What is their funding source(s)?
    • The database has been funded by the National Key R&D Program of China; National Natural Science Foundation of China; Singapore Academic Research Fund grant; Fundamental Research Funds for Central Universities; Innovation Project on Industrial Generic Key Technologies of Chongqing. Funding for open access charge: National Key R & D Program of China; National Natural Science Foundation of China. The funding information was found in their article in the Nucleic Acids Research journal.

Scientific quality of the database

  1. Does the content appear to completely cover its content domain?
    • How many records does the database contain?
      • There is no function within the database to show the total amount of records. See question below for claims made in corresponding paper.
    • What claims do the database owners make about coverage in the corresponding paper?
      • The database owners claim there is a total of 27,024 targets associated with human diseases. (Wang et al. 2019).
  2. What species are covered in the database? (If it is a very long list, summarize.)
    • The species covered in the database are human and human diseases. The list of human diseases is very extensive. Targets Search
  3. Is the database content useful? I.e., what biological questions can it be used to answer?
    • The database content is very useful. TTD can be used to find the proteins (and their sequences) of human diseases targeted by the corresponding drug. Both target protein and drug structure can be found. One can also identify mutations in target protein that disable the therapeutic drug. Influ NA Target Information. The identification of candidate target proteins is the first step to therapeutic drug development (Wang et al. 2019). TTD includes target interacting microRNAs and interacting proteins which can be used for drug development (Wang et al. 2019).
  4. Is the database content timely?
    • Is there a need in the scientific community for such a database at this time?
      • Yes there is a need at this time. There is a need at most times because diseases are constantly evolving and requiring updates on therapeutic drugs. TTD is especially useful at this time due to SARS-CoV-2. There is a section of the database dedicated to target proteins of SARS viruses Target and Drug Data for Coronavirus. There are 59 target/drug combination entries for Covid-19 Covid-19 Target Disease Search Results.
    • Is the content covered by other databases already?
      • Yes. Other databases have provided targets of different classes, drug-binding domains and targeted sites, target expression profiles in patients, activities of targeted agents, target-regulators, target-affiliated pathways, target–drug interaction networks, and target–disease associations. TTD is the first to arrange target sequence, binding domains, target sites, target activities, regulators, and interaction networks together. (Wang et al. 2019). See Introduction of Wang et al. for references to databases holding the information listed.
  5. How current is the database?
    • When did the database first go online?
    • How often is the database updated?
      • This could not be found
    • When was the last update?

General utility of the database to the scientific community

  1. Are there links to other databases? Which ones?
  2. Is it convenient to browse the data?
    • The database seems to be catered toward individuals that are looking for something specific. Each page requires a search to access data, so it isn't possible to browse all the data in that category. For example, when you click on the page titled Drug group, it requires a some type of search query. The only categories or pages that include a "Browse" option are the Drug Resistance Mutations and the Target Expression Profiles.
  3. Is it convenient to download the data?
    • In what file formats are the data provided?
      • Data can be downloaded in the form of .txt or .sdf files from the Download page. Individual entries cannot be downloaded, but full sets of data can be. For example, you can download a file of all the Protein Sequences of Protein/Peptide-Based COVID-19 Drugs.
  4. Evaluate the “user-friendliness” of the database: can a naive user quickly navigate the website and gather useful information?
    • The website is well-organized so you can navigate to different categories of information to search. However, you do need to have a good idea of what you are looking for.
    • There is a help section that explains how to navigate the database, and also acknowledges the other databases that they have obtained their information from.
    • There are many search options so you can be very specific about which category of data you are looking for. You can also do a customized search if you are unsure of which category to search.
    • I ran a sample query under the category Coronavirus search. I typed in "ACE2" and one result popped up under the Target ID T98390. The entry includes the name of the target (Human ACE2), synonyms, the gene name, its target-related diseases, the function, UniProt ID, the sequence, and more. These results all make sense, as the database is focused on human targets, diseases, etc.
  5. Access: Is there a license agreement or any restrictions on access to the database?
    • The information is copyrighted, but the database is free to access by anyone.

Summary Judgment

  1. Would you direct a colleague unfamiliar with the field to use it?
    • Yes I would recommend anybody curious on the status of drug development to use the TTD database. I think this database is very friendly to amateurs in the sense that you can look up the common name to a disease and receive results on the various drugs developed/being developed for the disease. For example, many people are curious about the status of drugs being tested for COVID-19. This database allows users to find drugs for COVID-19 and check their trial status.
  2. Is this a professional or "hobby" database? The "hobby" analogy means that it was that person's hobby to make the database. It could mean that it is limited in scope, done by one or a few persons, and/or seems amateur.
    • The TTD is a professional database. There is a team of 14 individuals listed on the formal citation for the database. There are possibly more contributors. The database is also part of a professional group, the Bioinformatics and Drug Design Group. The TTD also uses the most recent International Classification of Diseases Code (ICD-11) which is another indication of professionalism.
  3. Finally, please share why you chose this database in the first place, i.e., why did it interest you? Did it live up to the expectations you had when you chose it?
    • Both of our Week 6 projects concluded with a discussion on possible therapeutic strategies utilizing the SARS-CoV-2 Spike glycoprotein and the Human ACE-2. The TTD gave access to the drugs in development for both target proteins. The TTD exceeded expectations from when we first chose the database. I was not expecting to find so much information on the drugs themselves. I also did not expect to find data on target affiliated proteins and target interacting miRNA.

Scientific Conclusion

The Therapeutic Target Database (TTD) was successfully explored and assessed for general, scientific, and utilitarian quality. The database proves valuable as a resource for research on COVID-19 targeted therapeutics.

Acknowledgments

  • All questions answered in the database review were copied and pasted from the week 8 assignment page.
  • Macie Duran and Ian Wright conducted this assessment in collaboration.
    • Macie Duran completed the General Information Assessment, Utility Assessment, and the Purpose Section.
    • Ian Wright completed the Scientific Assessment, Summary Judgment, and Conclusion Section.

References

  • Ford, P. (2020, August 18). 'Real' Programming is an Elitist Myth. Wired.
  • Hitt, J. (2020, August 13). One IT Guy’s Spreadsheet-Fueled Race to Restore Voting Rights. Wired.
  • Yunxia Wang, Song Zhang, Fengcheng Li, Ying Zhou, Ying Zhang, Zhengwen Wang, Runyuan Zhang, Jiang Zhu, Yuxiang Ren, Ying Tan, Chu Qin, Yinghong Li, Xiaoxu Li, Yuzong Chen, Feng Zhu, Therapeutic target database 2020: enriched resource for facilitating research and early development of targeted therapeutics, Nucleic Acids Research, Volume 48, Issue D1, 08 January 2020, Pages D1031–D1041, https://doi.org/10.1093/nar/gkz981
  • Y. X. Wang, S. Zhang, F. C. Li, ..., Y. Z. Chen* & F. Zhu*. Therapeutic target database 2020: enriched resource for facilitating research and early development of targeted therapeutics. Nucleic Acids Research. 48(D1): D1031-D1041 (2020). PMID: 31691823
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