genomics-pipeline

Step 8: HLA Typing (T1K)

What This Does

Determines your HLA genotype (Human Leukocyte Antigen) from WGS data — the immune system genes that control tissue compatibility and drug hypersensitivity reactions.

Why

HLA alleles determine transplant compatibility, predisposition to autoimmune diseases, and severe adverse drug reactions (e.g., HLA-B57:01 and abacavir, HLA-B58:01 and allopurinol).

Tool

• T1K v1.0.9 — efficient HLA genotyping from sequencing reads

Docker Image

quay.io/biocontainers/t1k:1.0.9--h5ca1c30_0

Prerequisites

• Aligned BAM from step 2
• Pre-built HLA reference index from step 00 (t1k_idx/hlaidx_grch38)

Command

SAMPLE=your_sample
GENOME_DIR=/path/to/your/data

mkdir -p ${GENOME_DIR}/${SAMPLE}/hla

docker run --rm \
  --cpus 4 --memory 8g \
  -v ${GENOME_DIR}:/genome \
  quay.io/biocontainers/t1k:1.0.9--h5ca1c30_0 \
  run-t1k \
    -b /genome/${SAMPLE}/aligned/${SAMPLE}_sorted.bam \
    -f /genome/t1k_idx/hlaidx_grch38_rna_seq.fa \
    --preset hla \
    -o /genome/${SAMPLE}/hla/${SAMPLE}_t1k \
    -t 4

Output

• ${SAMPLE}_t1k_genotype.tsv — HLA allele calls per locus (A, B, C, DRB1, DQB1, etc.)
• Two alleles per locus (one per chromosome)

Alternative: HLA-LA

For a second opinion or when T1K results are ambiguous:

docker run --rm \
  --cpus 8 --memory 16g \
  -v ${GENOME_DIR}:/genome \
  jiachenzdocker/hla-la:latest \
  HLA-LA.pl \
    --BAM /genome/${SAMPLE}/aligned/${SAMPLE}_sorted.bam \
    --graph PRG_MHC_GRCh38_withIMGT \
    --sampleID ${SAMPLE} \
    --maxThreads 8 \
    --workingDir /genome/${SAMPLE}/hla_la

• Docker image is 4.5GB (includes pre-built graph)
• Slower but uses a different algorithm — useful for validation

Key HLA Alleles for Drug Safety

| Allele | Drug | Risk | |—|—|—| | HLA-B57:01 | Abacavir (HIV) | Severe hypersensitivity reaction | | HLA-B58:01 | Allopurinol (gout) | Stevens-Johnson syndrome / TEN | | HLA-B15:02 | Carbamazepine | Stevens-Johnson syndrome (SE Asian) | | HLA-A31:01 | Carbamazepine | Drug reaction with eosinophilia | | HLA-B*57:01 | Flucloxacillin | Drug-induced liver injury |

Important Notes

• HLA typing from WGS is approximate — clinical HLA typing for transplant or critical drug decisions uses dedicated high-resolution panels (sequence-based typing)
• WGS-based HLA is sufficient for pharmacogenomic screening (presence/absence of risk alleles)
• T1K requires the pre-built index from step 00 — do not skip the t1k-build.pl step
• Running both T1K and HLA-LA and comparing results increases confidence in the calls
• HLA region is the most polymorphic in the human genome — ambiguous calls are expected for rare alleles

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