Ian R. Wright Week 11

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Purpose

The purpose of this Journal Review is to understand the findings on G614 population mechanics presented in Korber et al. 2020 in order to present in Journal Club format to the LMU Bioinformatics Laboratory. The findings of this article may be used as inspiration and stepping stones for the class' final research project.

Evaluating our Scientific Source

Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus.

Korber, B., Fischer, W. M., Gnanakaran, S., Yoon, H., Theiler, J., Abfalterer, W., ... & Hastie, K. M. (2020). Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus. Cell, 182(4), 812-827.

  • DOI:

10.1016/j.cell.2020.06.043

  • Link to abstract ob PubMed:

https://pubmed.ncbi.nlm.nih.gov/32697968/

  • Link to article in PubMed Central:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332439/

  • Link to article in HTML format:

https://www.sciencedirect.com/science/article/pii/S0092867420308205

  • Link to full PDF version:

PDF

  1. Who owns the rights to the article? Look at the first page of the PDF version of the article for the © symbol. Generally, either the journal/publisher or the authors will hold the copyright.
    • Elsevier Incorporated
  2. How is the article available to you:
    • Is the article available “open access” (look for the words “open access” or the “unlocked” icon on the article website or the first page of the PDF) If YES, stop here.
      • Yes
  3. Is the article available online-only or both in print and online? Look on the journal website for a “subscription” link. If that page talks about subscribing to the print edition, then it is available in print. If not, it is available online-only.
    • It is available online and in print.
  4. Evaluating the source--the journal
    1. Who is the publisher of the journal?
      • Cell/Cell Press
    2. Is the publisher for-profit or non-profit?
      • For-Profit
    3. Is the publisher a scientific society (some scientific societies partner with a for-profit publisher, some act as their own non-profit publisher)
      • No
    4. Does the publisher belong to the Open Access Publishers Association?
      • No
    5. What country is the journal published in?
      • The Netherlands
    6. How long has the journal been in operation? (e.g., browse the archive for the earliest article published)
      • Since January 1974
    7. Are articles in this journal peer-reviewed?
      • Yes
    8. Provide a link to the scientific advisory board/editorial board of the journal.
    9. What is the journal impact factor (look to see if it is provided on the journal home page; often you can also find it through a Google search)?
      • Cell's 2019 impact factor is 38.637
  5. Evaluating the source--the article
    1. Is the article a review or primary research article?
      • Primary research
    2. On what date was the article submitted?
      • Initially submitted on April 29th 2020. Submitted again (revised) on June 10th 2020.
    3. On what date was the article accepted?
      • June 26th 2020
    4. Did the article undergo any revisions before acceptance?
      • Yes, this revision was submitted on June 10th 2020
    5. When was the article published?
      • July 3rd 2020
    6. What is the approximate elapsed time between submission and publication?
      • Approximately two months and five days
    7. What are the institutions with which the authors are affiliated?
      • Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM
      • La Jolla Institute for Immunology
      • Sheffield Biomedical Research Centre & Sheffield Bioinformatics Core, University of Sheffield
      • Sheffield Teaching Hospitals NHS Foundation Trust
      • Duke Human Vaccine Institute & Department of Surgery
      • Department of Molecular Microbiology, Washington University in Saint Louis
    8. Have the authors published other articles on this subject? How will you find this out?
      • This will be done by looking at each author's profile on PubMed.
        • Korber-Yes
        • Fischer-No
        • Gnanakaran-Yes
        • Yoon-No
        • Theiler-No
        • Abfalterer-No
    9. Is there a conflict of interest for any of the authors?
      • No, the authors declare no conflict of interest.
    10. Make a recommendation--based just on the information you have gathered so far, is this a good article to evaluate further? Why or why not?
      • Yes, just based upon the reputation of Cell, the journal which the article was published in. Cell has a reputation for publishing relevant articles that offer considerable advancements in their respective fields. Multiple authors have published work on SARS-CoV-2 and the authors that haven't have published work on HIV epidemiology.
  6. For your Conclusion section of this individual assignment, write a short reflection about what you learned by doing this exercise. Include in your answer what you knew previously about searching the biological literature and evaluating sources, and what you learned that was new that you learned today.

Preparation for Journal Club

Glossary of Terms

  • Antigenic Drift
    • A gradual change in surface antigens (pathogen's immune responding proteins). (J.M. Lackie et al., 2007, Page 30)
  • Pseudotyped virions
    • Virus particles produced via infiltration of host cell and usurpation of host biochemical machinery. (Murphy & Vile, 2002)
  • RT PCR Cts
    • PCR Cycle threshold. Ct is a unit of measurement produced through PCR. Ct value is inversely related to viral load. (Tom & Mina, 2020).
  • OC43
    • Human coronavirus infectious to humans and cattle. Enters host-cell through N-acetyl-9-O-acetylneuaminic acid receptor. (Lau et al., 2011).
  • Protomer
    • Subunits from which a larger structure is built (J.M. Lackie, et al., 2007, Page 348)
  • Furin (As in Furin Cleavage Site in Fig. 4A)
    • Eukaryotic endopeptidase with substrate specificity for sequence Arg-X-Lys/Arg-Arg. This sequence is cleavage site. "Furin is known to activate the haemagglutinin of fowl plague virus and will cleave the HIV envelope glycoprotein (gp160) into two portions, a necessary step in making the virus fusion-competent" (J.M. Lackie, et al., 2007, Page 168)
  • Endopeptidase
    • An enzyme that cleaves protein chains. Can also be called proteinases or proteolytic enzymes but formally refered to as peptidyl-peptide hydrolases (J.M. Lackie, et al., 2007, Page 143)
  • Nucleid Acid Extraction PCR Method
  • Simple Heat Inactivation PCR Method
  • Antibody Dependent Enhancement (ADE)
  • Non-neutralizing Antibodies


Korber et al. Outline

  • What is the importance or significance of this work?
    • Spike glycoprotein is the contact point between the SARS-CoV-2 virus and our human cells. ACE2 and the Spike glycoprotein have received a good portion of epidemiological focus during this pandemic. A mutation persisting in the viral population is something to be taken seriously. Antigenic drift involves the genetic drift of a pathogen's antigen, the receptor binding complex. Mutation within antigens has the potential to dramatically influence infectivity, not only in infection rate, but also in infection mechanistics and interactions with antibodies. The development of a successful and persistent vaccine requires a stable and predictable spike glycoprotein structure.
    • SARS-CoV-2 has undergone a population-wide shift from the D614 variant to the G614 variant. The G614 variant is now the dominant form of SARS-CoV-2.
  • What were the limitations in previous studies that led them to perform this work?
    • Until the development of the tool presented in the paper, there was no database dedicated to live tracking of SARS-CoV-2 mutations.
    • Included in this bioinformatic database is an indicator of potential positive selection for mutations arising in the virus. This is done by identifying variants that are becoming more prevalent in different geographic locations.
    • Many viral sequences available to the public contain gaps or incomplete portions of the genome. This results in a portion of the sequences being deemed 'useless' in terms of alignment and identification of point mutations.
  • How did they overcome these limitations?
    • The authors of the paper developed a website using sequence data from GISAID that highlights mutations occurring in the virus across the world. This database will also track dominance of arising variants. If increases in relative frequency of a particular variant are observed repeatedly in distinct geographic regions, then that variant becomes a candidate for analyzing for the possible selective advantages.
      • Identifying selective advantages can give insights to mechanisms of viral activity. The D614G mutation, for example, has become the subject of multiple studies focused on identifying the mechanistic implications of the spike protein.
      • D614 in the S1 subunit forms a hydrogen-bond with T589 of the adjacent S2 subunit. G614, however, does not have these bonding capabilities and therefore changes the interactions between S1 and S2 subunits. This change could possibly increase main-chain flexibility, modulate glycosylation at the nearby N616 site, and influence the dynamics of the nearby fusion peptide.
    • To overcome limitation of gaps and incomplete sequences, the authors developed a filtering method where the genomes are segmented into regional codes and then evaluated for efficacy in a sequence alignment/mutation comparison. The segments considered 'good' are incorporated into their database and used for mutation tracking.
  • What is the main result presented in this paper? (Hint: look at the last sentence of the introduction and restate it in plain English.)
    • The G614 mutant has become the dominant variant in the viral population. G614 mutant is associated with higher viral loads and greater infectivity.
  • What were the methods used in the study?
  • Briefly state the result shown in each of the figures and tables that you have been assigned in your group.
  • What are the important implications of this work?
  • What future directions should the authors take?
  • Give a critical evaluation of how well you think the authors supported their conclusions with the data they showed. Are there any limitations or major flaws to the paper?

Journal Club Presentation on Korber et al.

File:Journal Club week 11-Korber et al.pdf

Conclusion

Korber et al. was successfully reviewed for relevant information to be presented in the Week 12 Journal Club. Analysis of Korber et al. metadata was informative in the sense of evaluating the journal. I realized that a journal is not necessarily a publisher and that a publisher can produce multiple journals. Each journal can also have subjournals. In the case of this article, Elsevier Incorporated was the publisher. (I have now been seeing many Elsevier published articles, so I appreciate their reputation). Cell Press is a 'parent' journal to Cell, the journal in which Korber et al. was published. Lastly, in terms of metadata analysis, it was nice to get some practice exploring PubMed and the different information they include on their article pages.

Acknowledgements

References

  • Lackie, J. M. (Ed.). (2007). The dictionary of cell & molecular biology. Academic Press, 30, 348, 168, 143).
  • Lau, S. K., Lee, P., Tsang, A. K., Yip, C. C., Tse, H., Lee, R. A., ... & Yuen, K. Y. (2011). Molecular epidemiology of human coronavirus OC43 reveals evolution of different genotypes over time and recent emergence of a novel genotype due to natural recombination. Journal of virology, 85(21), 11325-11337.
  • Murphy, S. J., & Vile, R. G. (2002). Hybrid Adenoviral Vectors. In Adenoviral Vectors for Gene Therapy (pp. 481-531). Academic Press.
  • Tom, M. R., & Mina, M. J. (2020). To Interpret the SARS-CoV-2 Test, Consider the Cycle Threshold Value. Clinical Infectious Diseases.
  • https://www.biologyonline.com/dictionary/antibody-dependent-enhancement
  • https://www.biologyonline.com/dictionary/neutralizing-antibody
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