| | | |
Site-directed Mutantsa
|
LDA 3Fb
|
|---|
|
Mutation
c
|
N wt
d
|
N mut
e
|
NVP
|
EFV
|
ETR
|
max(
F
1)
|
max(
n
11
)
f
|
|
min(
cutoff
)
h
|
|
V179 M
|
67699
|
31
|
0.8-2.3
|
0.3-0.4
|
0.4-0.9
|
0.327 (EFV)
|
13 (ETR)
|
8/(8 + 10) (EFV)
|
1.35 (ETR)
|
|
H221 L
|
76783
|
31
|
4.2-5.0
|
1.5-1.6
|
1.1
|
0.118 (EFV)
|
2 (EFV)
|
2/(2 + 1) (EFV)
|
2.03 (ETR)
|
|
V179 Y
|
67699
|
17
|
0.2-0.5
|
< 0.2-0.2
|
< 0.1-0.2
|
0.063 (ETR)
|
16 (ETR)
|
16/(16 + 472) (ETR)
|
1.44 (ETR)
|
|
K219H
|
67913
|
129
|
1.3-2.2
|
1.0-1.8
|
1.1-1.8
|
0.047 (ETR)
|
14 (ETR)
|
14/(14 + 447) (ETR)
|
1.45 (ETR)
|
|
K219D
|
67913
|
161
|
1.4-3.8
|
1.3-2.2
|
0.4-2.0
|
0.044 (ETR)
|
24 (ETR)
|
24/(24 + 894) (ETR)
|
1.22 (ETR)
|
|
V179 N
|
67699
|
15
|
1.2-1.9
|
0.9-1.2
|
0.6-0.8
|
0.039 (ETR)
|
8 (ETR)
|
8/(8 + 391) (ETR)
|
1.50 (ETR)
|
|
T376S
|
15617
|
7415
|
2.8-3.4
|
1.5-2.0
|
1.6-2.1
|
0.035 (EFV)
|
135 (EFV)
|
135/(135 + 145) (EFV)
|
1.67 (ETR)
|
|
Y181S
|
72643
|
3
|
NA
|
NA
|
NA
|
0.019 (ETR)
|
3 (ETR)
|
3/(3 + 310) (ETR)
|
1.45 (ETR)
|
|
L100 V
|
77197
|
8
|
6.4 (1)
|
9.0-18.3 (2)
|
1.1-1.2 (2)
|
0.017 (ETR)
|
6 (ETR)
|
6/(6 + 678) (ETR)
|
1.63 (ETR)
|
|
Y181 F
|
72643
|
9
|
1.1-2.0
|
0.4-0.8
|
0.4-0.7
|
0.016 (ETR)
|
4 (ETR)
|
4/(4 + 503) (ETR)
|
1.33 (ETR)
|
|
K102L
|
72791
|
12
|
2.3-2.9
|
0.5-1.2
|
0.3-0.4
|
0.015 (ETR)
|
4 (ETR)
|
4/(4 + 505) (ETR)
|
1.77 (ETR)
|
|
K101 N
|
72175
|
94
|
5.0 (1)
|
2.8 (1)
|
0.8 (1)
|
0.015 (ETR)
|
4 (ETR)
|
4/(4 + 434) (ETR)
|
1.66 (ETR)
|
|
V106 L
|
75529
|
44
|
0.5-0.6
|
0.7-1.1
|
0.2-0.3
|
0.015 (ETR)
|
5 (ETR)
|
5/(5 + 617) (ETR)
|
1.69 (ETR)
|
|
E138 A
|
75869
|
1828
|
2.2-4.9
|
1.2-
3.6
|
2.8-
3.5
|
0.014 (ETR)
|
14 (ETR)
|
14/(14 + 157) (ETR)
|
2.10 (ETR)
|
|
M357T
|
44115
|
17866
|
0.9 (1)
|
1.2 (1)
|
NA
|
0.013 (ETR)
|
117 (ETR)
|
117/(117 + 199) (ETR)
|
1.88 (ETR)
|
|
T139R
|
76899
|
243
|
6.4-7.3
|
1.5-2.7
|
1.0-1.2
|
0.010 (ETR)
|
2 (ETR)
|
2/(2 + 137) (ETR)
|
2.22 (ETR)
|
|
E370G
|
75915
|
489
|
NA
|
NA
|
NA
|
0.007 (ETR)
|
2 (ETR)
|
1/(1 + 1) (EFV)
|
2.38 (ETR)
|
|
I135T
|
45829
|
18410
|
NA
|
NA
|
NA
|
0.006 (ETR)
|
52 (ETR)
|
52/(52 + 94) (ETR)
|
2.16 (ETR)
|
|
L234I
|
79037
|
98
|
0.6-1.0
|
1.6-2.3
|
0.9-1.1
|
0.004 (ETR)
|
1 (ETR)
|
1/(1 + 353) (ETR)
|
1.95 (ETR)
|
|
S379C
|
69973
|
3578
|
NA
|
NA
|
NA
|
0.001 (ETR)
|
1 (ETR)
|
1/(1 + 1) (ETR)
|
3.35 (ETR)
|
|
R206I
|
79051
|
8
|
1.0-1.7
|
0.4-0.7
|
0.5-0.9
|
NA
|
0 (ETR)
|
0/(0 + 102) (ETR)
|
2.33 (ETR)
|
|
S134N
|
79041
|
19
|
1.2-2.1
|
0.6-0.7
|
0.8-0.9
|
NA
|
0 (ETR)
|
0/(0 + 69) (ETR)
|
2.45 (ETR)
|
|
H221 C
|
76783
|
59
|
NA
|
NA
|
NA
|
NA
|
0 (ETR)
|
0/(0 + 20) (ETR)
|
2.73 (ETR)
|
|
I382T
|
78025
|
329
|
2.4-
6.7
|
0.9-1.7
|
0.7-2.4
|
NA
|
0 (ETR)
|
0/(0 + 2) (ETR)
|
3.30 (ETR)
|
|
D237E
|
78246
|
423
|
NA
|
NA
|
NA
|
NA
|
0 (EFV)
|
0/(0 + 3) (EFV)
|
3.67 (ETR)
|
|
N348T
|
74372
|
170
|
NA
|
NA
|
NA
|
NA
|
0 (ETR)
|
0/(0 + 0) (ETR)
|
4.05 (ETR)
|
|
E399G
|
66049
|
670
|
NA
|
NA
|
NA
|
NA
|
0 (ETR)
|
0/(0 + 0) (ETR)
|
4.10 (ETR)
|
|
G190 T
|
72912
|
10
|
> 67.4
|
7.8-14.9
|
0.6-0.7
|
NA
|
0 (EFV)
|
0/(0 + 2) (EFV)
|
4.16 (ETR)
|
|
Y188 F
|
76892
|
41
|
1.4-1.9
|
0.3-0.5
|
0.2-0.6
|
NA
|
0 (NVP)
|
0/(0 + 0) (NVP)
|
4.70 (NVP)
|
|
L283I
|
72462
|
5930
|
NA
|
NA
|
NA
|
NA
|
0 (ETR)
|
0/(0 + 0) (ETR)
|
5.01 (ETR)
|
|
K101 A
|
72175
|
50
|
8.8-13.4
|
4.1-5.6
|
1.5-1.8
|
NA
|
0 (EFV)
|
0/(0 + 3) (EFV)
|
5.04 (NVP)
|
|
K101 D
|
72175
|
7
|
13.3-18.9
|
5.7-6.8
|
1.0-1.3
|
NA
|
0 (EFV)
|
0/(0 + 3) (EFV)
|
5.08 (EFV)
|
|
T139K
|
76899
|
348
|
4.4-5.8
|
1.2-2.3
|
2.4-3.0
|
NA
|
0 (ETR)
|
0/(0 + 0) (ETR)
|
5.10 (ETR)
|
|
T165L
|
75078
|
183
|
NA
|
NA
|
NA
|
NA
|
0 (ETR)
|
0/(0 + 0) (ETR)
|
5.81 (ETR)
|
|
T386A
|
59810
|
1756
|
NA
|
1.6 (1)
|
0.5 (1)
|
NA
|
0 (NVP)
|
0/(0 + 0) (NVP)
|
6.07 (NVP)
|
|
V241M
|
78771
|
23
|
4.7-5.6
|
1.0-1.8
|
0.8-1.2
|
NA
|
0 (NVP)
|
0/(0 + 0) (NVP)
|
6.90 (NVP)
|
|
I382L
|
78025
|
228
|
NA
|
NA
|
NA
|
NA
|
0 (NVP)
|
0/(0 + 0) (NVP)
|
7.30 (NVP)
|
|
G335S
|
65035
|
1877
|
NA
|
NA
|
NA
|
NA
|
0 (ETR)
|
0/(0 + 0) (ETR)
|
7.55 (ETR)
|
|
E399D
|
66049
|
10697
|
NA
|
NA
|
NA
|
NA
|
0 (ETR)
|
0/(0 + 0) (ETR)
|
7.98 (ETR)
|
|
R358K
|
70517
|
5995
|
NA
|
NA
|
NA
|
NA
|
0 (NVP)
|
0/(0 + 0) (NVP)
|
8.06 (NVP)
|
- aFold-Change range from 3 measurements, unless otherwise indicated between brackets.
- FC > Biological Cut-Off (BCO) in bold, FC ≤ BCO in italic; BCO for NVP is 6.0, BCO for EFV is 3.3 and BCO for ETR is 3.2.
- bSummarized for the three non-nucleoside RT inhibitors (NNRTI).
- cTop 40 mutations, ranked by max(LDA F1) descending, then by min(LDA cutoff) ascending. Mutations shown are from the list of 124 NNRTI mutations with RWF ≥ 0 and LDA cutoff > 0 for NVP, EFV and ETR. Known NNRTI positions or novel mutations listed in [32, 33] are shown in bold.
- dFrequency of wild-type (not within a mixture) in LDA data set.
- eFrequency of mutation (not within a mixture) in LDA data set.
- fn11 is the number of samples with amino acid mutation having a predicted phenotype above the LDA cutoff.
- gn01 is the number of samples with wild type amino acid having a predicted phenotype above the LDA cutoff.
- hCutoff in log Fold-Change (taking the wild-type and mutation frequency percentages as prior probabilities in the LDA can result in cutoff values outside of the range of the predicted phenotypes).
