Background

The major histocompatibility complex (MHC) is the most polymorphic locus in the human genome, and the linear reference represents one of many possible haplotypes. For HLA typing — central to organ-transplant matching, disease association, and immunotherapy — calling against a single haplotype underperforms on cohorts whose ancestry is poorly represented in the reference. The diagnostic cost of that gap is non-trivial.

Objective

CliMHC builds a clinically deployable graph representation of the MHC region from ancestry-stratified haplotype-resolved assemblies and benchmarks its diagnostic concordance against current HLA-typing workflows. The aim is a graph and a calling pipeline that hospitals can drop into existing infrastructure without changing their wet-lab protocols.

Aims

• Curate haplotype-resolved MHC assemblies across ancestry strata represented in the catchment populations of our hospital partners.
• Build and version a clinical MHC graph with full provenance and a published diff between graph versions.
• Benchmark concordance against current short-read HLA typing pipelines in retrospective cohorts (n ≈ 4 200 across both hospitals).
• Pilot prospective use in a small set of transplant cross-matching cases under the relevant ethics protocol.

Externally funded (2024–2028) in partnership with two university hospitals — a histocompatibility laboratory and an immunology service. Pipeline code is open source; graph releases are versioned and ancestry-coded but contain no individual-level data.