Matthew R Allegretti Week 11

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Week 11 Assignment

Purpose

  • To construct a presentation for our research project.

Methods and Results

Subject 4

Visit 1

  • 3 Clones

Visit 4

  • 13 Clones

Subject 9

Visit 1

  • 5 Clones

Visit 4

  • 11 Clones

Subject 11

Visit 1

  • 7 Clones

Visit 4

  • 9 Clones

Subject 14

Visit 1

  • 6 Clones

Visit 4

  • 10 Clones
  • 64 Total Clones

Variability

We measured variability at each position by identifying the locations with major mutations at them according to boxshade. We also identified positions with more than one major mutation present. Both were found by comparing them to the consensus sequence from Huang et al. (2005).

Data and Files

From Week 10

From Week 11

Conclusion

We discovered that all 4 subjects studied contained major mutations at multiple positions within the amino acid sequence. We analyzed the structural locations of each major mutation and attempted to analyze how they may affect the overall function of the protein. Upon further research, we discovered that site 317 was a key position linked with antibody interactions, Edlefsen et al. (2015). In both of the rapid progressors, this site was unchanged from the Huang et al. (2005) sequence. In both moderate progressors, however, all subjects had an identical T to A mutation. I believe that this locations may be what distinguishes the difference in progression groups between these subjects, despite having identical dS/dN values.

References

  • Week 10
    • Pulled my progress from last week onto this week's page
  • Edlefsen, P. T., Rolland, M., Hertz, T., Tovanabutra, S., Gartland, A. J., Magaret, C. A., et al. (2015). Comprehensive sieve analysis of breakthrough HIV-1 sequences in the RV144 vaccine efficacy trial. PLoS Comput Biol, 11(2), e1003973.
  • Huang, C. C., Tang, M., Zhang, M. Y., Majeed, S., Montabana, E., Stanfield, R. L., ... & Wyatt, R. (2005). Structure of a V3-containing HIV-1 gp120 core. Science, 310 (5750), 1025-1028.
  • Kirchherr, J. L., Hamilton, J., Lu, X., Gnanakaran, S., Muldoon, M., Daniels, M., Kasongo, W., et al. (2011). Identification of amino acid substitutions associated with neutralization phenotype in the human immunodeficiency virus type-1 subtype C gp120. Virology, 409(2), 163-174. DOI: 10.1016/j.virol.2010.09.031
  • Kwong, P. D., Wyatt, R., Robinson, J., Sweet, R. W., Sodroski, J., & Hendrickson, W. A. (1998). Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature, 393(6686), 648-659. DOI: 10.1038/31405
  • Markham, R.B., Wang, W.C., Weisstein, A.E., Wang, Z., Munoz, A., Templeton, A., Margolick, J., Vlahov, D., Quinn, T., Farzadegan, H., & Yu, X.F. (1998). Patterns of HIV-1 evolution in individuals with differing rates of CD4 T cell decline. Proc Natl Acad Sci U S A. 95, 12568-12573. doi: 10.1073/pnas.95.21.12568

Acknowledgements

  • Anu Varshneya
    • We communicated electronically and met outside of class once.

While I worked with the people noted above, this individual journal entry was completed by me and not copied from another source.

Useful links

Course Home Page

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