Swiss army knife of HLA Nomenclature

Note:

Release 1.1.1 has extensive Serolgy related updates and affects Serology related data. Please rebuild the cache database if there's a missing Serology error.

pyard-import --re-install

Or set py-ard requirements to be py-ard<=1.1.1 for your dependency.

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.

1. Installation
   • Install From PyPi
   • Install With Homebrew
   • Install From Source
2. Using py-ard
   • Using py-ard from Python
   • Using py-ard from R
   • Perform Reduxtion
   • DRBX blending
   • Expand/Lookup MAC
3. Command Line Tools
   • pyard-import Import Reference Data
   • pyard-status Show Statuses of Databases
   • pyard Redux
   • pyard-csv-reduce Batch Mode Redux
4. py-ard REST Webservice
5. Docker Deployment

py-ard works with Python 3.8 and higher.

pip install py-ard

Note: With py-ard version 1.0.0 and higher, the redux API has changed. If your use requires the older API, please install with pip install py-ard==0.9.2

On 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/tap

Install py-ard

brew install py-ard

Homebrew will notify you as new versions of py-ard are released.

python3 -m venv venv
source venv/bin/activate

python setup.py install

See 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 pyard discovers an invalid Allele, it'll throw an Invalid Exception, not silently return an empty result.

Import pyard package.

import pyard

Initialize ARD object with a version of 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. This may be removed when your computer restarts. You can specify a different, more permanent directory for the cached data.

import pyard.ard

ard = pyard.init('3510', data_dir='/tmp/py-ard')

As MAC data changes frequently, you can choose to refresh the MAC code for current IMGT HLA database version.

ard.refresh_mac_codes()

The default initialization is to use the latest version of IPD-IMGT/HLA database.

import pyard

ard = pyard.init()

You can check the current version of IPD-IMGT/HLA database.

ard.get_db_version()

Note: Previous to version of 1.0.0 release of py-ard, there was redux and redux_gl methods on ard. They have been consolidated so that redux 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 method.

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'

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:MN

Reduce 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*15:07

The 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'

py-ard works well from R as well. Please see Using pyard 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 IMGT_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 IMGT database
versions.

options:
  -h, --help            show this help message and exit
  --list                Show Versions of available IMGT Databases
  -i IMGT_VERSION, --imgt-version IMGT_VERSION
                        Import supplied IMGT_VERSION DB Version
  -d DATA_DIR, --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 mapping

Run 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 database

Import particular version of IMGT 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-mac

You can skip loading MAC if you don't need by using --skip-mac

$ pyard-import --imgt-version 3150 --skip-mac

Show 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-status

Use --data-dir to specify an alternate directory for cached database files.

$ pyard-status  --data-dir ~/.pyard/
IMGT DB Version: Latest (3440)
There is a newer IMGT release than version 3440
Upgrade to latest version '3510' with 'pyard-import --re-install'
File: /Users/pbashyal/.pyard/pyard-Latest.sqlite3
Size: 533.37MB
-------------------------------------------
|Table Name          |Rows                |
|-----------------------------------------|
|dup_g               |                  59|
|dup_lgx             |                   1|
|g_group             |               14223|
|p_group             |               18872|
|lgx_group           |               14223|
|exon_group          |               12934|
|p_not_g             |                1681|
|xx_codes            |                1517|
|who_group           |               30785|
|alleles             |               32504|
|exp_alleles         |                  60|
|who_alleles         |               30523|
|mac_codes           |             1089379|
-------------------------------------------

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 IMGT_VERSION] [-g GL_STRING]
             [-r {G,P,lg,lgx,W,exon,U2}] [--splits SPLITS]

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_DIR
                        Data directory to store imported data
  -i IMGT_VERSION, --imgt-version IMGT_VERSION
                        IPD-IMGT/HLA db to use for redux
  -g GL_STRING, --gl GL_STRING
                        GL String to reduce
  -r {G,P,lg,lgx,W,exon,U2}, --redux-type {G,P,lg,lgx,W,exon,U2}
                        Reduction Method
  --splits SPLITS       Find Broad and Splits

Reduce 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*01:01

py-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/B65

pyard-csv-reduce can be used to batch process a CSV file with HLA typings. See documentation for detailed information about all the options.

Run 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

$ python app.py
 * Serving Flask app 'app'
 * Debug mode: on
WARNING: This is a development server. Do not use it in a production deployment. Use a production WSGI server instead.
 * Running on all addresses (0.0.0.0)
 * Running on http://127.0.0.1:8080
 * Running on http://10.0.1.37:8080
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-build

builds a Docker image named pyard-service:latest

Build the docker and run it with:

make docker

The endpoint should then be available at localhost:8080