Predicting the Onset of AIDS Robert Arnold, Alex Cardenas, Zeb Russo LMU Biology Department...
-
Upload
cornelia-jordan -
Category
Documents
-
view
221 -
download
2
Transcript of Predicting the Onset of AIDS Robert Arnold, Alex Cardenas, Zeb Russo LMU Biology Department...
Predicting the Onset of AIDS
Robert Arnold, Alex Cardenas, Zeb RussoLMU Biology Department
10/5/2011
Outline• What causes a subject to develop AIDS from HIV and
what separates AIDS from HIV? Focusing on dS/dN ratio
• The definition of AIDS, the subjects affected, and their similarities, ALIVE information
• New hypothesis involving the division of subjects into those with AIDS, trending towards AIDS, and AIDS free trending away
• Research comparison, proving assumptions incorrect• Further comparisons between the subjects with AIDS
and those without• Comparing our results with our paper
dS/dN ratio related to AIDS development
• determined that low dS/dN ratios, subjects that select either for nonsynonymous mutation or not against it were the subjects to develop AIDS
• The subjects picked were 4, 9, 11, and 14, all with 0.0 dS/dN ratios along with subject 10 with a 0.2 and subject 1 with a 0.3
Outline• What causes a subject to develop AIDS from HIV and
what separates AIDS from HIV? Focusing on dS/dN ratio
• The definition of AIDS, the subjects affected, and their similarities, ALIVE information
• New hypothesis involving the division of subjects into those with AIDS, trending towards AIDS, and AIDS free trending away
• Research comparison, proving assumptions incorrect• Further comparisons between the subjects with AIDS
and those without• Comparing our results with our paper
AIDS and CD4 counts
• CDC definition of AIDS is a CD4 count below 200
• Once diagnosed, cannot be reversed
• Makes our first hypothesis irrelevant since all ‘rapid progressors’ drop below 200, AKA all 6 have AIDS– Subjects 1, 3, 4, 10, 11, 15
Outline• What causes a subject to develop AIDS from HIV and
what separates AIDS from HIV? Focusing on dS/dN ratio
• The definition of AIDS, the subjects affected, and their similarities, ALIVE information
• New hypothesis involving the division of subjects into those with AIDS, trending towards AIDS, and AIDS free trending away
• Research comparison, proving assumptions incorrect• Further comparisons between the subjects with AIDS
and those without
Revised hypothesis separating those with AIDS
from others• Separated into 3 categories
– Those with AIDS: 1, 3, 4, 10, 11, 15– Those trending to AIDS: 7, 8, 9, 14– Those free of and trending away from AIDS: 2, 5,
6, 12, 13
• New vision; which subjects developed AIDS?• Began to focus on ALIVE research to go
beyond Markham’s 4 year period
Development of two new questions
• Since we can tell who has AIDS, we would now like to determine whether there are any similar clones of the env gene across the AIDS subjects
• Does a median ds/dn ratio below 1.0 or lower determine whether you will get AIDS or not?
Outline• What causes a subject to develop AIDS from HIV and
what separates AIDS from HIV? Focusing on dS/dN ratio
• The definition of AIDS, the subjects affected, and their similarities, ALIVE information
• New hypothesis involving the division of subjects into those with AIDS, trending towards AIDS, and AIDS free trending away
• Research comparison, proving assumptions incorrect• Further comparisons between the subjects with AIDS
and those without• Comparing our results with our paper
Our division of the Patients
Random clonal comparison
• To determine whether there were any similarities between clones of those who developed AIDS during the study and those at risk, we performed a ClustalW on a random selection of two clones from each subject
2 Clones Rooted Tree
Comparison of dS/dN
Subject No. of observations CD4
Median intravisit nucleotide
differences among clones
Virus copy number (×103)
Annual rate of CD4 T cell decline
Slope of change in intravisit nucleotide differences per clone
per year
Slope of divergence (% nucleotides mutated
from baseline consensus sequence
per year) Median dS/dN
AIDS
Subject 4 4 1,028 0.9 6.8 −593 4.64 2.09 0
Subject 10 5 833 1.71 99.3 −363 3.16 1 0.2
Subject 11 4 753 2.27 62.2 −363 1.11 0.32 0
Subject 15 4 707 15.16 171 −362 −2.94 0.68 0.7
Subject 3 5 819 1.82 302.5 −294 0.53 0.74 1
Subject 1 3 464 5.64 307.6 −117 5.1 1.55 0.3
At Risk
Subject 7 5 1,072 2.27 317.6 −392 −0.79 1.35 1.3
Subject 8 7 538 1.24 209 −92 1.68 1.16 0.5
Subject 9 8 489 9.49 265 −11 1.58 1.21 0
Subject 14 9 523 1 50.9 −51 1.69 0.6 0
Not at Risk
Subject 2 5 715 1.64 21.6 30 1.32 0.49 1.8
Subject 5 5 749 2.5 260.6 −41 0.06 0.5 1.4
Subject 6 7 405 2.82 321.4 52 1.92 0.82 0.4
Subject 12 6 772 2.8 5.1 44 0.62 0.13 0.9
Subject 13 5 671 0.87 1.7 53 0.53 0.28 3.5
Neither Assumption is correct
• Using the original data from the Bedrock website, we determined who actually developed AIDS over the full study
• 1, 3, 4, 6, 7, 8, 9, 10, 11, 14, 15
• Only 2, 5, 12 and 13 avoided the progression to AIDS over the course of the study
Outline• What causes a subject to develop AIDS from HIV and
what separates AIDS from HIV? Focusing on dS/dN ratio
• The definition of AIDS, the subjects affected, and their similarities, ALIVE information
• New hypothesis involving the division of subjects into those with AIDS, trending towards AIDS, and AIDS free trending away
• Research comparison, proving assumptions incorrect• Further comparisons between the subjects with AIDS
and those without• Comparing our results with our paper
2 Clones Rooted Tree Redux
Comparison of dS/dN
Subject No. of observations CD4
Median intravisit nucleotide
differences among clones
Virus copy number (×103)
Annual rate of CD4 T cell decline
Slope of change in intravisit nucleotide differences per clone
per year
Slope of divergence (% nucleotides mutated
from baseline consensus sequence
per year) Median dS/dN
AIDS
Subject 4 4 1,028 0.9 6.8 −593 4.64 2.09 0
Subject 10 5 833 1.71 99.3 −363 3.16 1 0.2
Subject 11 4 753 2.27 62.2 −363 1.11 0.32 0
Subject 15 4 707 15.16 171 −362 −2.94 0.68 0.7
Subject 3 5 819 1.82 302.5 −294 0.53 0.74 1
Subject 1 3 464 5.64 307.6 −117 5.1 1.55 0.3
At Risk
Subject 7 5 1,072 2.27 317.6 −392 −0.79 1.35 1.3
Subject 8 7 538 1.24 209 −92 1.68 1.16 0.5
Subject 9 8 489 9.49 265 −11 1.58 1.21 0
Subject 14 9 523 1 50.9 −51 1.69 0.6 0
Not at Risk
Subject 2 5 715 1.64 21.6 30 1.32 0.49 1.8
Subject 5 5 749 2.5 260.6 −41 0.06 0.5 1.4
Subject 6 7 405 2.82 321.4 52 1.92 0.82 0.4
Subject 12 6 772 2.8 5.1 44 0.62 0.13 0.9
Subject 13 5 671 0.87 1.7 53 0.53 0.28 3.5