hlaont

Confidence-aware, full-field HLA typing from Oxford Nanopore (ONT) R10 long reads, designed for population-scale sequencing.

Hlaont does the following:

• Types 41 HLA/MIC/TAP genes.
• Estimates copy number per gene rather than assuming diploidy at every locus.
• Reports C4A/C4B total copy number and long/short-form composition (the complement C4 segmental duplication).
• Flags novel alleles (novel:intronic, novel:utr, novel:synonymous, novel:nonsynonymous, novel:null, extension).
• Accepts FASTQ or BAM/CRAM input, and can use real read-backed phase (HP/PS tags) when available.

Requirements

• Python ≥ 3.11
• minimap2 and samtools on PATH (external CLI tools, not pip-installable — install via conda/bioconda: conda install -c bioconda minimap2 samtools)

Installation

# from source
git clone https://github.com/aleixcanalda/hlaont.git
cd hlaont
pip install -e .

# or, once published:
# pip install hlaont
# conda install -c bioconda hlaont

First-time setup

The package ships the anchor set, models and a pre-extracted assembly bundle, but the template pool is built from IPD-IMGT/HLA once before hlaont run will work:

hlaont update-db --db-dir hlaont_db/   # downloads IPD-IMGT/HLA and builds the pool into hlaont_db/
hlaont run SAMPLE_ID reads.fastq --db-dir hlaont_db/ --out-dir OUT/

--db-dir can also be set once with export HLAONT_DB=hlaont_db/; without either, the pool lives inside the installed package.

hlaont update-anchors --db-dir hlaont_db/ rebuilds the anchor set against a new pool (maintainers only; needs cd-hit-est on PATH).

Usage

# FASTQ input
hlaont run SAMPLE_ID reads.fastq --out-dir OUT/

# BAM/CRAM input (region set auto-derived from the @SQ header — no build/reference flag needed)
hlaont run SAMPLE_ID --bam aligned.bam --out-dir OUT/
hlaont run SAMPLE_ID --bam aligned.cram --reference ref.fa --out-dir OUT/

# Use real read-backed phase (HP/PS tags), when the input BAM has them
hlaont run SAMPLE_ID --bam phased.bam --phased --out-dir OUT/

Each run writes, into --out-dir:

Run hlaont run --help, hlaont update-db --help, or hlaont update-anchors --help for the full flag list.

License

hlaont's own code is MIT — see LICENSE. The distributed package also contains Badread's error model (GPL-3.0-only), so the package as a whole is MIT AND GPL-3.0-only.

resources/anchors/vendor/ ports a 136-allele anchor set from FuFiHLA (MIT); resources/models/vendor/ ports an ONT R10.4.1 error model from Badread (GPLv3). See each NOTICE.md/license file for full attribution. If you use hlaont, please also cite FuFiHLA (10.1093/bioinformatics/btag231).