Chris Rhodes Week 4

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HIV Experiment Outline

  1. Question: Based on some of the conclusions presented in the Discussion section of the Markham Paper that tried to relate various immune responses to the different progressor types I thought it would be interesting to look at the genetic diversity and divergence of some of the subjects in each of the three progressor groups through the use of phylogenetic trees and see if there were any discernible patterns within or between progressor groups and hypothesize about what these patterns could tell us about the immune response of the subject. By using phylogenetic trees (both rooted and unrooted) as visual indicators of diversity and divergence, our experiment hopes to determine the pattern of immune response employed by each subject and determine whether or not the pattern of immune response used is related to the progressor type of the subject.
  2. As hypothesized by the paper, non-progressors are thought to use a broadly effective immune response which targets and cuts down any virus that replicates past a certain threshold. Subsequently, there is strong selection against change for any surviving virus strain because mutation could cause increased replication past the immune threshold resulting in eradication of the new mutant. On the other hand, rapid progressors are thought to use a far more specific style of immune response that, instead of targeting all of the viral variants such as non-progressors, targets only the most prevalent viral strain encountered. Due to this, there is strong selection for change in the rapid progressor viruses because the immune system can be easily escaped through mutation which makes the new variant unrecognizable to the rapid progressors hyper-specific immune cells. Based on these findings, it is my view that when observing the phylogenetic trees of non-progressors we will see evidence of low diversity and divergence with the trees having short clustered branches with minimal vertical branching due to any radically different variants being quickly snuffed out. For rapid progressors, I expect to see high diversity and divergence with the trees having long horizontal branches stemming from multiple different ancestor strains. For moderate progressors, since the differences in diversity and divergence between rapid and moderate progressors in the paper didn't achieve significance, I'm expecting to see trees that closely resemble the patterns of rapid progressors but perhaps with less diverse ancestor strains or slightly less branching.
  3. We will be using all the visits and variants of two subjects from each progressor group to conduct this experiment:
    • Rapid Progressors: Subjects 3 and 11
    • Moderate Progressors: Subjects 7 and 8
    • Non-progressors: Subjects 12 and 13
    • We chose these subjects mainly due to the sample sizes of their total visits. All of these subjects have 50 or less variants allowing us to create a phylogenetic tree using all the variants collected throughout the study whereas with other subjects we would have to exclude some of the variants to make the tree which could greatly affect the pattern the tree would take. While more than just the subjects we chose fit our parameters, we felt that some subjects, such as Subject 2 whose time points skip three years, would not provide us with adequate data to make reasonable conclusions and were thus excluded from our experiment to preserve the integrity of the results.

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