Mia Huddleston Week 11
Electronic Notebook
Purpose
The purpose of this week is to finish the presentation comparing amino acid mutations to genetic diversity and relating this to possible structure change of gp120 and the V3 region.
Methods and Results
Things we should still do:
- Explain why we chose our subjects
- significance test
- continue with clustldist - explain what data means
- most different from starting point
- divergence
- max distance values
- types of mutations
- look more at structure
- create outline
- background info
- Today, we located each of the mutations on each part of the structure provided in the Huang et al paper. We also found what kind of mutations each were.
- We did this by looking at an amino acid chart and found what two amino acids were being exchanged or what was being deleted
- We then looked at the possible change of structure that could occur and also looked at this on the gp120 structure provided by the Huang et al paper.
- Because there were so many mutations for some of the subjects (24 for subject 10) we found the most prevalent mutations that were more likely to effect the structure and will add those to our presentation:
- Subject 10
- C → R: polar → basic
- S → R: polar → basic
- E → D → G: acidic → acidic → polar
- I → T: non polar (hydrophobic) → polar
- A → R: non polar → basic
- V → A → G: non polar → non polar → polar
- D → A: acidic → non polar
- R → G: basic → polar
- Subject 3
- R → deletion
- V → A → G: non polar → non polar → polar
- Subject 10
HIV Structure Project:
- What is your question?
- Does diversity and divergence increase within the amino acid sequences over time more within the rapid progressors compared to non-progressors?
- Make a prediction about the answer to your question before you begin your analysis.
- Since divergence and diversity increases over time within the DNA sequences for all progressor types, and more so within the rapid progress ors, we would expect to see more diversity within the amino acid sequences over time within the rapid progressors.
- Which subjects, visits, and clones will you use to answer your question?
- For rapid progressors we are looking at subject 3 and 10's first and last visits and for non-progressors we are looking at subject 12 and 13's first and last visits. These were chosen based on similar number of visits.
Conclusion
In conclusion, we found sequence alignments, rooted trees, and clustldists for each of the four subjects looking at each of their first and last visits using the biology workbench. There appeared to be more diversity within the rapid progressors, especially for subject 10, but p-values were not found. There was not as much of a difference for subject 3, but we concluded that this could be because there are less total clones to analyze for subject 3. In the future we would want to look at more subjects with more clones and more visits. We also looked at where the mutations occurred in gp120 and what kind of mutations occurred using the Huang et al. figure. When comparing the types of mutations found for each subject we could determine where this mutation was and possibly how it could effect the function of gp120.
Data and Files
Presentation
Acknowledgements
Avery Vernon-Moore and I worked together to create the "Defining Your HIV Structure Research Project" portion. Dr. Dahlquist provided help in the writing and designing of our research project. While I worked with the people noted above, this individual journal entry was completed by me and not copied from another source.
References
- ExPASY Translate tool
- BEDROCK HIV Problem Space
- UniProt Knowledgebase (UniProt KB)
- 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
Useful links
User Page: Mia Huddleston
Bioinfomatics Lab: Fall 2016
Class Page: Bioinfomatics Laboratory, Fall 2016