git 路径： https://github.com/AlexanderDilthey/MHC-PRG

HLAPRG is an algorithm for HLA type inference from next-generation sequencing data.
官方还开发了一款：HLAPRG:LA 现在叫：HLA*LA，后面测试
步骤：
1 使用一种PRG算法（Population Reference Graph）将reads 比对到HLA gene上

2. 对于每一个比对上的基因，都找到一对潜在的等位基因，最大限度地观察到与位点对齐的reads的概率
   支持6位，

不建议在外显子数据中使用 HLA*PRG
仅支持hg19

测试：

$  perl -c ./HLAtypeinference.pl
Can't locate simpleHLA.pm in @INC (you may need to install the simpleHLA module) (@INC contains: /etc/perl /usr/local/lib/x86_64-linux-gnu/perl/5.30.0 /usr/local/share/perl/5.30.0 /usr/lib/x86_64-linux-gnu/perl5/5.30 /usr/share/perl5 /usr/lib/x86_64-linux-gnu/perl/5.30 /usr/share/perl/5.30 /usr/local/lib/site_perl /usr/lib/x86_64-linux-gnu/perl-base) at ./HLAtypeinference.pl line 12.
BEGIN failed--compilation aborted at ./HLAtypeinference.pl line 12.

解决：

export PERLLIB=/cygene/software/biosoftware/MHC-PRG/src

$ perl -c ./HLAtypeinference.pl
./HLAtypeinference.pl syntax OK

可以分4步，也可以combine in 1步：

./HLAtypeinference.pl --actions pnai --sampleIDs SAMPLEID --BAMs /path/to/indexed/bam.bam --referenceGenome /path/to/referenceGenome/as/one/fasta/file

注意：

1. sampleid 指的是bam中的sample id。
2. bam必须sorted and indexed。
3. reference 是HG38？

报错：

$ /software/biosoftware/MHC-PRG/src/HLAtypeinference.pl --actions pnai --sampleIDs CP60005015_Normal --BAMs CP60005015-C01.Normal.sortedByCoord.bam --referenceGenome /database/GATK_resource_bundle/hg38/Homo_sapiens_assembl

Please set variable $genome_graph_file to an existing file - the current value ../tmp2/GS_nextGen/hla/derived/Homo_sapiens.GRCh37.60.dna.chromosome.ALL.blockedHLAgraph_k25.ctx is not accessible. at /software/biosoftware/MHC-PRG/src/HLAtypeinference.pl line 118.

还没解决。。。

Currently HLA*PRG should only be applied to B37-aligned BAM files. We plan to update the pipeline to deal with GRCh38-based BAMs.

可以放弃了。。。

HLA*LA

git https://github.com/DiltheyLab/HLA-LA
安装：
conda install hla-la
或手动安装：
mkdir HLA-LA HLA-LA/bin HLA-LA/src HLA-LA/obj HLA-LA/temp HLA-LA/working HLA-LA/graphs
cd HLA-LA/src; git clone https://github.com/DiltheyLab/HLA-LA.git .
make all
../bin/HLA-LA --action testBinary

image.png

下载数据：
cd HLA-LA/graphs
wget http://www.well.ox.ac.uk/downloads/PRG_MHC_GRCh38_withIMGT.tar.gz
tar -xvzf PRG_MHC_GRCh38_withIMGT.tar.gz

index the graph
../bin/HLA-LA --action prepareGraph --PRG_graph_dir ../graphs/PRG_MHC_GRCh38_withIMGT

测试安装：
samtools index NA12878.mini.cram
./HLA-LA.pl --BAM NA12878.mini.cram --graph PRG_MHC_GRCh38_withIMGT --sampleID NA12878 --maxThreads 7

运行HLA*A：
./HLA-LA.pl --BAM /path/to/indexed.bam --graph PRG_MHC_GRCh38_withIMGT --sampleID $mySampleID --maxThreads 7