xHLA: Fast and accurate HLA typing from short read sequence data

The Human Leukocyte Antigen (HLA) gene complex on human chromosome 6 is one of the most polymorphic regions in the human genome, and contributes in large part to the diversity of the immune system. Accurate typing of HLA genes with short read sequencing data has historically been difficult due to the sequence similarity between the polymorphic alleles. xHLA iteratively refines the mapping results at the amino acid level to achieve 99 to 100% 4-digit typing accuracy for both class I and II HLA genes, taking only about 3 minutes to process a 30X whole genome BAM file on a desktop computer.

Installation

Simply pull from Docker hub:

docker pull humanlongevity/hla

Or, compile docker image yourself:

cd docker
make build
make deploy

Usage

Run xHLA caller directly on an indexed BAM file generated using BWA-mem against hg38 reference without alt contigs:

docker run -v `pwd`:`pwd` -w `pwd` humanlongevity/hla \
    --sample_id test --input_bam_path tests/test.bam \
    --output_path test

For other types of BAMs, pre-processing is required. Please check details here.

Output is a JSON file that lists 12 HLA alleles, 2 for each of the HLA genes:

{
 "subject_id": "test",
 "creation_time": "2017-10-04T18:59:34Z",
 "report_version": "1.2",
 "report_type": "hla_typing",
 "sample_id": "test",
 "hla": {
  "alleles": [
   "A*01:01",
   "A*02:01",
   "B*13:02",
   "B*37:01",
   "C*06:02",
   "C*06:02",
   "DPB1*04:01",
   "DPB1*04:01",
   "DQB1*02:02",
   "DQB1*05:01",
   "DRB1*07:01",
   "DRB1*10:01"
  ]
 }
}

Citation

Xie et al. (2017) Fast and accurate HLA typing from short-read next-generation sequence data with xHLA. PNAS doi:10.1073/pnas.1707945114

License

The HLA Typing Software Code (the "Code") is made available by Human Longevity, Inc. ("HLI") on a non-exclusive, non-sublicensable, non-transferable basis solely for non-commercial academic research use. Commercial use of the Code is expressly prohibited. If you would like to obtain a license to the Code for commercial use, please contact HLI at [email protected]. HLI MAKES NO REPRESENTATIONS OR WARRANTIES WHATSOEVER, EITHER EXPRESS OR IMPLIED, WITH RESPECT TO THE CODE PROVIDED HEREUNDER. IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE WITH RESPECT TO CODE ARE EXPRESSLY DISCLAIMED. THE CODE IS FURNISHED "AS IS" AND "WITH ALL FAULTS" AND DOWNLOADING OR USING THE CODE IS UNDERTAKEN AT YOUR OWN RISK. TO THE FULLEST EXTENT ALLOWED BY APPLICABLE LAW, IN NO EVENT SHALL HLI BE LIABLE, WHETHER IN CONTRACT, TORT, WARRANTY, OR UNDER ANY STATUTE OR ON ANY OTHER BASIS FOR SPECIAL, INCIDENTAL, INDIRECT, PUNITIVE, MULTIPLE OR CONSEQUENTIAL DAMAGES SUSTAINED BY YOU OR ANY OTHER PERSON OR ENTITY ON ACCOUNT OF USE OR POSSESSION OF THE CODE, WHETHER OR NOT FORESEEABLE AND WHETHER OR NOT HLI HAS BEEN ADVISED OF THE POSSIBILITY OF SUCH DAMAGES, INCLUDING WITHOUT LIMITATION DAMAGES ARISING FROM OR RELATED TO LOSS OF USE, LOSS OF DATA, DOWNTIME, OR FOR LOSS OF REVENUE, PROFITS, GOODWILL, BUSINESS OR OTHER FINANCIAL LOSS.