1. Predicting the Onset of AIDS
Robert Arnold, Alex Cardenas, Zeb Russo
LMU Biology Department
10/5/2011

2. 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

3. 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

4. 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

5. 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

6. 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?

7. Our division of the Patients

8. 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

9. 2 Clones Rooted Tree

10. 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
Subject 10 5
833
1.71
99.3
−363
3.16 1
0.2
Subject 11
753
2.27
62.2
1.11
0.32
Subject 15
707
15.16
171
−362
−2.94
0.68
0.7
Subject 3
819
1.82
302.5
−294
0.53
0.74
Subject 1 3
464
5.64
307.6
−117
5.1
1.55
0.3
At Risk
Subject 7
1,072
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
Subject 14 9
523
50.9
−51
1.69
0.6
Not at Risk
Subject 2
715
1.64
21.6 30
1.32
0.49
1.8
Subject 5
749
2.5
260.6
−41
0.06
1.4
Subject 6
405
2.82
321.4 52
1.92
0.82
0.4
Subject 12 6
772
2.8 44
0.62
0.13
Subject 13
671
0.87
1.7 53
0.28
3.5

11. 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

12. 2 Clones Rooted Tree Redux

13. 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
Subject 10 5
833
1.71
99.3
−363
3.16 1
0.2
Subject 11
753
2.27
62.2
1.11
0.32
Subject 15
707
15.16
171
−362
−2.94
0.68
0.7
Subject 3
819
1.82
302.5
−294
0.53
0.74
Subject 1 3
464
5.64
307.6
−117
5.1
1.55
0.3
At Risk
Subject 7
1,072
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
Subject 14 9
523
50.9
−51
1.69
0.6
Not at Risk
Subject 2
715
1.64
21.6 30
1.32
0.49
1.8
Subject 5
749
2.5
260.6
−41
0.06
1.4
Subject 6
405
2.82
321.4 52
1.92
0.82
0.4
Subject 12 6
772
2.8 44
0.62
0.13
Subject 13
671
0.87
1.7 53
0.28
3.5