Predicting the Onset of AIDS
Robert Arnold, Alex Cardenas, Zeb Russo
LMU 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
Slope of divergence
Median intravisit
Slope of change in
(% nucleotides
nucleotide
intravisit nucleotide mutated from baseline
differences among Virus copy number Annual rate of CD4 differences per clone consensus sequence
clones
(×103)
T cell decline
per year
per year)
CD4
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
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
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
At Risk
Not at Risk
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
Slope of divergence
Median intravisit
Slope of change in
(% nucleotides
nucleotide
intravisit nucleotide mutated from baseline
differences among Virus copy number Annual rate of CD4 differences per clone consensus sequence
clones
(×103)
T cell decline
per year
per year)
CD4
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
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
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
At Risk
Not at Risk