Sierra 2.2.7-1

This is a post-release of HIVDB algV8.6.1 which updated comments for PIs and INSTIs. No score or rule changes were involved.

Sierra 2.2.7

Two major changes were done in this version.

• Release HIVDB algV8.6
• Change post-alignment parameter SEQUENCE_SHRINKAGE_BAD_QUALITY_MUT_PREVALENCE from 0.1% to 0.01%, which defines the cutoff for low prevalence (unusual/atypical) mutation in the "sequence shrinkage" process

HIVDB algV8_5 => algV8_6 Changes

8 rules were changed in this version:

• Changed Scores of rule H51Y : 5 to 10 (BIC), 5 to 10 (DTG).
• Changed Scores of rule T66I : 0 to 5 (BIC), 0 to 5 (DTG).
• Changed Scores of rule S230R : 0 to 10 (BIC), 0 to 20 (DTG), 15 to 20 (EVG), 15 to 20 (RAL).
• Changed Scores of rule R263K : 15 to 25 (BIC), 15 to 25 (DTG), 15 to 25 (RAL).
• Changed Scores of rule Q148HKR + N155H : 5 to 10 (BIC), 5 to 10 (DTG).
• Changed rule L74IM + Y143ACGHRS to L74FM + Y143ACGHRS.
• Changed rule L74IM + Q148HKR to L74FM + Q148HKR and its scores 5 to 10 (BIC), 5 to 10 (DTG), 0 to 10 (EVG), 0 to 10 (RAL).
• Changed Scores of rule T97A + Q148HKR : 5 to 10 (BIC), 5 to 10 (DTG).

Following listed 74 affected patterns of mutations:

pattern	count	BIC	DTG	EVG	RAL
R263K	17	15 => 25	15 => 25	30	15 => 25
L74M + T97A + Y143R	8	10	10	30	70
T66I	8	0 => 5	0 => 5	60	15
L74M + Y143R	7	10	10	15	60
T97A + Y143C + S230R	6	10 => 20	10 => 30	45 => 50	85 => 90
L74M + G140S + Q148H	5	50 => 55	50 => 55	90 => 100	90 => 100
L74M + Q95K + T97A + Y143R	5	10	10	40	80
Y143C + N155H + S230R	5	20 => 30	20 => 40	90 => 95	135 => 140
H51Y	4	5 => 10	5 => 10	15	15
S230R	4	0 => 10	0 => 20	15 => 20	15 => 20
N155H + S230R	4	10 => 20	10 => 30	75 => 80	75 => 80
L74M + T97A + Y143C + S230R	4	15 => 25	15 => 35	50 => 55	85 => 90
G140S + Q148H + N155H	3	60 => 65	60 => 65	150	150
L74M + T97A + Y143G	3	10	10	30	70
L74M + T97A + Y143R + E157Q	3	10	10	40	80
Q148R + N155H	3	40 => 45	40 => 45	120	120
T97A + G140S + Q148H	3	50 => 55	50 => 55	100	100
Y143C + S230R	3	10 => 20	10 => 30	30 => 35	75 => 80
E138K + G140A + Q148R + N155H	2	90 => 95	90 => 95	180	180
H51Y + E92Q + G140S + Q148K + N155H	2	85 => 95	85 => 95	225	195
L74I + T97A + Y143C + S230R	2	15 => 20	15 => 30	50	85 => 90
L74M + T97A + Y143R + G163K	2	10	10	45	85
L74M + T97A + Y143S + S230R	2	15 => 25	15 => 35	50 => 55	85 => 90
E92Q + G140S + Q148K + N155H	2	80 => 85	80 => 85	210	180
E92Q + G140S + Q148R + N155H	2	75 => 80	75 => 80	210	180
T97A + Y143C + G163R + S230R	2	15 => 25	15 => 35	65 => 70	100 => 105
Y143C + G163R + S230R	2	15 => 25	15 => 35	50 => 55	90 => 95
E138A + S147G + Q148R + N155H	1	60 => 65	60 => 65	195	135
E138K + G140A + Q148K + N155H	1	95 => 100	95 => 100	180	180
E138K + Q148R + N155H + G163K	1	65 => 70	65 => 70	150	150
E138K + Y143C + N155H + G163R + S230R	1	35 => 45	35 => 55	125 => 130	165 => 170
E157Q + R263K	1	25 => 35	25 => 35	40	25 => 35
E92Q + E138K + Y143C + N155H + S230R	1	45 => 55	45 => 65	165 => 170	180 => 185
G140S + Q148H + N155H + E157Q	1	60 => 65	60 => 65	160	160
G140S + Q148K + N155H	1	65 => 70	65 => 70	150	150
G140S + Q148K + N155H + G163R	1	70 => 75	70 => 75	165	165
G140S + Q148R + N155H + E157Q	1	60 => 65	60 => 65	160	160
H51Y + E92Q + G140S + Q148K + N155H + G163R	1	90 => 100	90 => 100	240	210
H51Y + G140S + Q148K	1	55 => 60	55 => 60	105	105
H51Y + T66A + N155H	1	15 => 20	15 => 20	135	90
L74I + G140S + Q148R + R263K	1	65 => 70	65 => 70	120	105 => 115
L74M + E138K + G140C + Q148R + E157Q	1	80 => 85	80 => 85	130 => 140	130 => 140
L74M + E138T + G140S + Q148H	1	80 => 85	80 => 85	120 => 130	120 => 130
L74M + E92Q + Q148R	1	40 => 45	40 => 45	120 => 130	90 => 100
L74M + G140A + Q148R	1	50 => 55	50 => 55	90 => 100	90 => 100
L74M + G140C + Q148R	1	50 => 55	50 => 55	90 => 100	90 => 100
L74M + G140C + Q148R + G163R	1	55 => 60	55 => 60	105 => 115	105 => 115
L74M + G140S + Q148R	1	50 => 55	50 => 55	90 => 100	90 => 100
L74M + G140S + Q148R + E157Q	1	50 => 55	50 => 55	100 => 110	100 => 110
L74M + Q95K + T97A + Y143C + S230R	1	15 => 25	15 => 35	60 => 65	95 => 100
L74M + Q95K + Y143C + S230R	1	15 => 25	15 => 35	45 => 50	85 => 90
L74M + T97A + E138A + Y143C	1	20	20	45	85
L74M + T97A + E138K + Y143C + S230R	1	25 => 35	25 => 45	65 => 70	100 => 105
L74M + T97A + E138K + Y143R	1	20	20	45	85
L74M + T97A + Y143C + G163R + S230R	1	20 => 30	20 => 40	70 => 75	100 => 105
L74M + T97A + Y143G + G163R	1	15	15	50	85
L74M + T97A + Y143H + G163R	1	15	15	50	85
L74M + Y143C	1	10	10	15	60
L74M + Y143C + N155H + S230R	1	25 => 35	25 => 45	95 => 100	135 => 140
L74M + Y143R + E157Q	1	10	10	25	70
N155H + R263K	1	25 => 35	25 => 35	90	75 => 85
T66I + T97A + G163R	1	0 => 5	0 => 5	85	40
T66I + T97A + N155H	1	10 => 15	10 => 15	130	85
T66I + Y143C	1	5 => 10	5 => 10	70	75
T66K + L74M + G140S + Q148R + E157Q	1	65 => 70	65 => 70	160 => 170	160 => 170
T97A + E138A + G140S + Q148H	1	80 => 85	80 => 85	130	130
T97A + E138K + Q148R + N155H + G163K	1	70 => 80	70 => 80	160	160
T97A + G140S + Q148R + N155H + G163R	1	70 => 80	70 => 80	175	175
T97A + Y143S + S230R	1	10 => 20	10 => 30	45 => 50	85 => 90
Y143C + E157Q + S230R	1	10 => 20	10 => 30	40 => 45	85 => 90
Y143C + G163K + S230R	1	10 => 20	10 => 30	45 => 50	90 => 95
Y143C + N155H + E157Q + S230R	1	20 => 30	20 => 40	100 => 105	145 => 150
Y143S + N155H + G163K + S230R	1	20 => 30	20 => 40	105 => 110	150 => 155
Y143S + S230R	1	10 => 20	10 => 30	30 => 35	75 => 80

Bugfix 2.2.6-1

Fixed a mistake in the ASI file of ANRS v28 (doesn't affect scores).

Algorithms update; bugfix

Six changes were introduced since v2.2.4 (I forgot to release v2.2.5 here).

1. Add Docker support.
2. ANRS Algorithm has been upgraded to v28 (Apr 2018):
   Since v28, drug code DRV/r and DTG have been removed from the ASI file. Instead, we now use DRV/r_QD, DRV/r_BID, DTG_QD and DTG_BID to indicate the rules for low and high dose DRV/r and DTG, respectively.
3. Fixed a bug which caused incomplete spreadsheet output. The bug was triggered when a reverse complement sequence was submitted.
4. A warning was added when the submitted sequence was a reverse complement.
5. A boolean value "isReverseComplement" was added to the GraphQL output "SequenceAnalysis" object.
6. HIVDB Drug Resistance Algorithm has been updated to version 8.5 in this release. Following one modification was made to reflect this upgrade:
   A New ARV "BIC" was added to "INSTI" section in drug display options of HIVDB Program.

You can now use this command to fetch Sierra image with Docker:

docker pull hivdb/sierra:2.2.6

To start a instance running Sierra:

docker run -it --publish=8080 hivdb/sierra dev

Then you can access local Sierra web service through this URL:

http://localhost:8080/WebApplications/rest/graphql

Bugfix release 2.2.4

This release contains changes from v2.2.3 and v2.2.4 since v2.2.3 has never publicly released.

Bug Fixes:

1. Limitations were applied to sequences analysis (GraphQL) in this update to prevent server out-of-resources issue.
2. Instead of returning an empty resistance result, mutations analysis and pattern analysis (GraphQL) are now able to return a totally sensitive report if all presented gene positions are wild type amino acids.
3. Improve speed of the regression test.

Release 2.2.2

This update added a new field to GraphQL object Mutation:

...
mutations {
  ...
  isSDRM  # indicate a mutation is a Surveillance Drug
          # Resistance Mutation (SDRM) or not
  ...
}
...

Post-release 2.2.1-1

Minor modifications made to ANRS algorithm:

The ANRS algorithm was updated to version 27 (see PDF) on January 9. We have since made two modifications to this update.

The ANRS algorithm has different scores for dolutegravir (DTG) 50mg QD and DTG 50mg BID as well as for darunavir/r (DRV/r) 600mg/100mg BID and DRV/r 800mg QD. We have modified the ASI implementation of the algorithm as follows. The rules for low and high dose DTG are indicated by DTGQD and DTGBID, respectively. The rules for low and high dose DRV/r are indicated by DRV/r_QD and DRV/r_BID, respectively.

For users of HIValg, DTG will contain the same rules as DTGQD and DRV/r will contain the same rules as those for DRV/r_QD.

Upgrade "Rega" and "ANRS" algorithms

This version upgrade following two algorithms:

1. Rega: from v9.1.0 to v10.0.0
2. ANRS: from v26 to v27

"NucAmino" Release

The switch from LAP to NucAmino has been accompanied by several additional changes to the process of aligning submitted sequences to HIV-1 pol:

1. Each submitted sequence is aligned to the complete HIV-1 pol reference subtype B sequence rather than to PR, RT, and IN separately. This results in slightly different handling of the small number of sequences that previously exhibited alignment anomalies at the PR/RT and RT/IN boundaries.
2. We have also introduced stricter criteria for quality control at the beginning and end of sequences.
3. We have introduced a new set of warnings for sequences (i) containing very short regions of PR, RT, or IN; (ii) containing poor quality at its boundaries; and (iii) containing inappropriate concatenations of noncontiguous regions of pol.

The complete release notes of this version will be available at https://hivdb.stanford.edu/page/program-updates/ once we deployed this version.