Swiss army knife of HLA Nomenclature
Note:
- With
py-ard>=2.0.0, the dependency on Pandas library has been removed.
Human leukocyte antigen (HLA) genes encode cell surface proteins that are important for immune regulation. Exons
encoding the Antigen Recognition Domain (ARD) are the most polymorphic region of HLA genes and are important for
donor/recipient HLA matching.
The history of allele typing methods has played a major role in determining resolution and ambiguity of reported HLA
values. Although
HLA nomenclature has not
always conformed to the same standard, it is now defined
by The WHO Nomenclature Committee for Factors of the HLA System. py-ard
is aware of the variation in historical resolutions and grouping and is able to translate from one representation to
another based on alleles published quarterly by IPD/IMGT-HLA.
py-ard works with Python 3.9 and higher (Python 3.8-3.13 are supported, but 3.9+ is recommended).
pip install py-ardOn macOS, py-ard can be installed using Homebrew package manager.
This is very handy for using the command line versions of the tool without having to create virtual environments.
First time, you'd need to tap the nmdp-bioinformatics tap.
brew tap nmdp-bioinformatics/tapInstall py-ard
brew install py-ardHomebrew will notify you as new versions of py-ard are released.
Checkout the py-ard source code.
git clone https://github.com/nmdp-bioinformatics/py-ard.git
cd py-ardCreate and activate virtual environment. Install the py-ard dependencies.
make venv
source venv/bin/activate
make installSee Our Contribution Guide for open source contribution to py-ard.
py-ard can be used in a program to reduce/expand HLA GL String representation. If py-ard discovers an invalid Allele,
it'll throw an Invalid Exception, not silently return an empty result.
Import and initialize pyard package.
The default initialization is to use the latest version of IPD-IMGT/HLA database.
import pyard
ard = pyard.init()Initialize py-ard with a particular version of IPD/IMGT-HLA database.
import pyard
ard = pyard.init('3510')When processing a large numbers of typings, it's helpful to have a cache of previously calculated reductions to make
similar typings reduce faster. The cache size of pre-computed reductions can be changed from the default of 1,000 by
setting cache_size argument. This increases the memory footprint but will significantly increase the processing times
for large number of reductions.
import pyard
max_cache_size = 1_000_000
ard = pyard.init('3510', cache_size=max_cache_size)By default, the IPD-IMGT/HLA data is stored locally in $TMPDIR/pyard-$USER/. This temporary location may be removed when your computer restarts.
Alternatively, you can specify a different, more permanent directory for the cached data.
import pyard
ard = pyard.init('3510', data_dir='~/.py-ard/')
# Creating ~/.py-ard/pyard-3510.sqlite3 as cache.
# Version: 3510As MAC data changes frequently, you can choose to refresh the MAC code for current IPD/IMGT-HLA database version.
ard.refresh_mac_codes()You can check the current version of IPD-IMGT/HLA database.
ard.get_db_version()You can choose to skip loading MAC codes if not needed (improves initialization time) by specifying load_mac=False during initialization.
import pyard
ard = pyard.init('3510', load_mac=False)Customize reduction behavior by passing a config dictionary to pyard.init().
import pyard
config = {
'reduce_serology': True, # Reduce serology typings (default: True)
'reduce_v2': True, # Reduce V2 alleles (default: True)
'reduce_3field': True, # Reduce 3-field alleles (default: True)
'reduce_P': True, # Reduce P group alleles (default: True)
'reduce_XX': True, # Reduce XX codes (default: True)
'reduce_MAC': True, # Reduce MAC codes (default: True)
'reduce_shortnull': True, # Reduce short nulls (default: True)
'ping': True, # Use ping mode (default: True)
'verbose_log': False, # Enable verbose logging (default: False)
'ARS_as_lg': False, # Treat ARS as lg (default: False)
'strict': True, # Strict validation mode (default: True)
'ignore_allele_with_suffixes': () # Tuple of suffixes to ignore (default: ())
}
ard = pyard.init('3510', config=config)Note: The redux method in ARD object handles both GL Strings and individual alleles.
Reduce a single locus HLA Typing by specifying the allele/MAC/XX code and the reduction method to redux.
allele = "A*01:01:01"
ard.redux(allele, 'G')
# >>> 'A*01:01:01G'
ard.redux(allele, 'lg')
# >>> 'A*01:01g'
ard.redux(allele, 'lgx')
# >>> 'A*01:01'Reduce an ambiguous GL String
# Reduce GL String
#
ard.redux("A*01:01/A*01:01N+A*02:AB^B*07:02+B*07:AB", "G")
# 'B*07:02:01G+B*07:02:01G^A*01:01:01G+A*02:01:01G/A*02:02'You can also reduce serology based typings.
ard.redux('B14', 'lg')
# >>> 'B*14:01g/B*14:02g/B*14:03g/B*14:04g/B*14:05g/B*14:06g/B*14:08g/B*14:09g/B*14:10g/B*14:11g/B*14:12g/B*14:13g/B*14:14g/B*14:15g/B*14:16g/B*14:17g/B*14:18g/B*14:19g/B*14:20g/B*14:21g/B*14:22g/B*14:23g/B*14:24g/B*14:25g/B*14:26g/B*14:27g/B*14:28g/B*14:29g/B*14:30g/B*14:31g/B*14:32g/B*14:33g/B*14:34g/B*14:35g/B*14:36g/B*14:37g/B*14:38g/B*14:39g/B*14:40g/B*14:42g/B*14:43g/B*14:44g/B*14:45g/B*14:46g/B*14:47g/B*14:48g/B*14:49g/B*14:50g/B*14:51g/B*14:52g/B*14:53g/B*14:54g/B*14:55g/B*14:56g/B*14:57g/B*14:58g/B*14:59g/B*14:60g/B*14:62g/B*14:63g/B*14:65g/B*14:66g/B*14:68g/B*14:70Qg/B*14:71g/B*14:73g/B*14:74g/B*14:75g/B*14:77g/B*14:82g/B*14:83g/B*14:86g/B*14:87g/B*14:88g/B*14:90g/B*14:93g/B*14:94g/B*14:95g/B*14:96g/B*14:97g/B*14:99g/B*14:102g'| Reduction Type | Description |
|---|---|
G |
Reduce to G Group Level |
P |
Reduce to P Group Level |
lg |
Reduce to 2 field ARD level (append g) |
lgx |
Reduce to 2 field ARD level |
W |
Reduce/Expand to full field(4,3,2) WHO nomenclature level |
exon |
Reduce/Expand to 3 field level |
U2 |
Reduce to 2 field unambiguous level |
S |
Reduce to Serological level |
import pyard
pyard.dr_blender(drb1='HLA-DRB1*03:01+DRB1*04:01', drb3='DRB3*01:01', drb4='DRB4*01:03')
# >>> 'DRB3*01:01+DRB4*01:03'py-ard supports not only reducing to various types but helps in expanding and
looking up MAC representation. See MAC Service UI for detail.
You can also use py-ard to expand MAC codes. Use expand_mac method on ard.
ard.expand_mac('HLA-A*01:BC')
# 'HLA-A*01:02/HLA-A*01:03'Find the corresponding MAC code for an allele list GL String.
ard.lookup_mac('A*01:02/A*01:01/A*01:03')
# A*01:MNReduce a MAC code or an allele list GL String to CWD reduced list.
ard.cwd_redux("B*15:01:01/B*15:01:03/B*15:04/B*15:07/B*15:26N/B*15:27")
# => B*15:01/B*15:07The above 2 methods can be chained to get back a MAC code that has a CWD reduced version.
ard.lookup_mac(ard.cwd_redux("B*15:01:01/B*15:01:03/B*15:04/B*15:07/B*15:26N/B*15:27"))
# 'B*15:AH'Validate a GL String:
ard.validate('A*01:01+A*02:01^B*07:02+B*08:01')
# Returns True if valid, raises exception if invalidExpand XX codes:
ard.expand_xx('A*01:XX')
# Returns all alleles matching the XX codeFind similar alleles:
ard.similar_alleles('A*01:AB')
# Returns list of similar allele namesCheck allele types:
ard.is_mac('A*01:AB') # Check if MAC code
ard.is_serology('A1') # Check if serology
ard.is_v2('A*0101') # Check if V2 allele
ard.is_XX('A*01:XX') # Check if XX code
ard.is_shortnull('A*01:01N') # Check if short null
ard.is_null('A*01:01N') # Check if null alleleFind serology relationships:
ard.find_broad_splits('A10') # Find broad/split relationships
ard.find_associated_antigen('Bw4') # Find associated antigensConvert V2 to V3:
ard.v2_to_v3('A*0101') # Convert V2 allele to V3 formatpy-ard works well from R as well. Please
see Using py-ard from R language
page for detailed walkthrough.
Various command line interface (CLI) tools are available to use for managing local IPD-IMGT/HLA cache database, running impromptu reduction queries and batch processing of CSV files.
For all tools, use --imgt-version and --data-dir to specify the IPD-IMGT/HLA database version and the directory
where the SQLite files are created.
pyard-import helps with importing and reinstalling of prepared IPD-IMGT/HLA and MAC data.
Use pyard-import -h to see all the options available.
$ pyard-import -h
usage: pyard-import [-h] [--list] [-i IPD_VERSION] [-d DATA_DIR]
[--v2-to-v3-mapping V2_V3_MAPPING] [--refresh-mac]
[--re-install] [--skip-mac]
py-ard tool to generate reference SQLite database. Allows updating db with
custom V2 to V3 mappings. Displays the list of available IPD/IMGT-HLA database
versions.
options:
-h, --help show this help message and exit
--list Show Versions of available IPD/IMGT-HLA Databases
-i, --ipd-version IPD_VERSION
Import supplied IPD/IMGT-HLA DB Version
-d, --data-dir DATA_DIR
Data directory to store imported data
--v2-to-v3-mapping V2_V3_MAPPING
V2 to V3 mapping CSV file
--refresh-mac Only refresh MAC data
--re-install reinstall a fresh version of database
--skip-mac Skip creating MAC mappingRun pyard-import without any option to download and prepare the latest version of IPD-IMGT/HLA and MAC data.
$ pyard-import
Created Latest py-ard database$ pyard-import --db-version 3.29.0
Created py-ard version 3290 databaseImport particular version of IPD/IMGT-HLA database and replace the v2 to v3 mapping table from a CSV file.
$ pyard-import --imgt-version 3.29.0 --v2-to-v3-mapping map2to3.csv
Created py-ard version 3290 database
Updated v2_mapping table with 'map2to3.csv' mapping file.pyard-import --imgt-version 3340 --re-install$ pyard-import --v2-to-v3-mapping map2to3.csv$ pyard-import --imgt-version 3450 --refresh-macYou can skip loading MAC if you don't need by using --skip-mac
$ pyard-import --imgt-version 3150 --skip-macShow the statuses of all py-ard databases
pyard-status goes through all the available databases and checks all the tables that should be available. This is very
helpful to show all the databases, number of rows in each table, any missing tables and the stored IPD-IMGT/HLA version.
$ pyard-statusUse --data-dir to specify an alternate directory for cached database files.
$ pyard-status --data-dir ~/.pyard/
=============================================
IPD/IMGT-HLA DB Version: Latest (3530)
There is a newer IPD/IMGT-HLA release than version 3530
Upgrade to latest version '3630' with 'pyard-import --re-install'
File: /Users/pbashyal-nmdp/.pyard/pyard-Latest.sqlite3
Size: 577.42MB
---------------------------------------------
|Table Name | Rows|
|-------------------------------------------|
|alleles | 39,977|
|cwd2 | 336|
|dup_g | 70|
|exon_group | 13,406|
|exp_alleles | 91|
|g_group | 14,736|
|lgx_group | 14,736|
|mac_codes | 1,138,229|
|p_group | 21,534|
|p_not_g | 1,709|
|serology_broad_split_mapping | 23|
|serology_mapping | 131|
|shortnulls | 176|
|v2_mapping | 11|
|who_alleles | 37,619|
|who_group | 36,576|
|xx_codes | 2,019|
---------------------------------------------pyard command can be used for quick reductions from the command line. Use --help option to see all the available
options.
$ pyard --help
usage: pyard [-h] [-v] [-d DATA_DIR] [-i IPD_VERSION] [-g GL_STRING]
[-r {G,P,lg,lgx,W,exon,U2,S}] [--splits SPLITS] [--validate]
[--cwd CWD] [--expand-mac EXPAND_MAC] [--lookup-mac LOOKUP_MAC]
[--expand-xx EXPAND_XX] [--expand EXPAND]
[--similar SIMILAR_ALLELE] [--non-strict] [--verbose]
py-ard tool to redux GL String
options:
-h, --help show this help message and exit
-v, --version IPD-IMGT/HLA DB Version number
-d, --data-dir DATA_DIR
Data directory to store imported data
-i, --ipd-version IPD_VERSION
IPD-IMGT/HLA db to use for redux
-g, --gl GL_STRING GL String to reduce
-r, --redux-type {G,P,lg,lgx,W,exon,U2,S}
Reduction Method
--splits SPLITS Find Broad and Splits
--validate Validate the provided GL String
--cwd CWD Perform CWD redux
--expand-mac EXPAND_MAC
Expand MAC to Allele List
--lookup-mac LOOKUP_MAC
Lookup MAC for an Allele List
--expand-xx EXPAND_XX
Expand XX code to Allele List
--expand EXPAND Expand MAC or XX code to Allele List
--similar SIMILAR_ALLELE
Find Similar Alleles with given prefix
--non-strict Use non-strict mode
--verbose Use verbose modeReduce from command line by specifying any typing with -g or --gl option and the reduction method with -r
or --redux-type option.
$ pyard -g 'A*01:AB' -r lgx
A*01:01/A*01:02
$ pyard --gl 'DRB1*08:XX' -r G
DRB1*08:01:01G/DRB1*08:02:01G/DRB1*08:03:02G/DRB1*08:04:01G/DRB1*08:05/ ...
$ pyard -i 3290 --gl 'A1' -r lgx # For a particular version of DB
A*01:01/A*01:02/A*01:03/A*01:06/A*01:07/A*01:08/A*01:09/A*01:10/A*01:12/ ...If the -r option is left out, pyard will print out the result of all reduction methods.
$ pyard -g 'A*01:01:01:01'
Reduction Method: G
-------------------
A*01:01:01G
Reduction Method: P
-------------------
A*01:01P
Reduction Method: lg
--------------------
A*01:01g
Reduction Method: lgx
---------------------
A*01:01
Reduction Method: W
-------------------
A*01:01:01:01
Reduction Method: exon
----------------------
A*01:01:01
Reduction Method: U2
--------------------
A*01:01py-ard knows about the broad/splits of serology and DNA, you can find by using --splits option to pyard command.
$ pyard --splits "A*10"
A*10 = A*25/A*26/A*34/A*66
$ pyard --splits B14
B14 = B64/B65Validate a GL String:
$ pyard -g 'A*01:01+A*02:01' --validatePerform CWD reduction:
$ pyard --cwd 'B*15:01:01/B*15:01:03/B*15:04'
B*15:01Expand MAC or XX codes:
$ pyard --expand-mac 'A*01:AB'
A*01:01/A*01:02
$ pyard --expand-xx 'A*01:XX'
A*01:01/A*01:02/A*01:03/...Lookup MAC code:
$ pyard --lookup-mac 'A*01:01/A*01:02'
A*01:ABFind similar alleles:
$ pyard --similar 'A*01:AB'
A*01:AB
A*01:ACpyard-reduce-csv can be used to batch process a CSV file with HLA typings. See documentation for
detailed information about all the options.
Generate sample configuration and CSV files:
$ pyard-reduce-csv --generate-sample
Created reduce_conf.json
Created sample.csv
Created reduce_conf_glstring.json
Created sample_glstring.csvReduce a CSV file using a configuration:
$ pyard-reduce-csv -c reduce_conf.jsonRun py-ard as a service so that it can be accessed as a REST service endpoint.
To start in debug mode, you can run the app.py script. The endpoint should then be available
at localhost:8080
$ python3 app.py
py-ard version: 2.0.0
IMGT version: 3631
`ConnexionMiddleware.run` is optimized for development. For production, run using a dedicated ASGI server.
INFO: Started server process [5344]
INFO: Waiting for application startup.
INFO: Application startup complete.
INFO: Uvicorn running on http://127.0.0.1:8080 (Press CTRL+C to quit)For deploying to production, build a Docker image and use that image for deploying to a server.
Build the docker image:
make docker-buildbuilds a Docker image named nmdpbioinformatics/pyard-service:2.0.0.linux-amd64
Build the docker and run it with:
make dockerThe endpoint should then be available at localhost:8080
