Full resolution HLA and KIR genes annotation for human genome assemblies

Area of Science:

• Genetics and Immunology
• Bioinformatics and Computational Biology

Background:

• Human Leukocyte Antigen (HLA) and Killer cell Immunoglobulin-like Receptor (KIR) genes are crucial for immune responses and disease association.
• High polymorphism in HLA and KIR regions challenges traditional short-read sequencing methods.
• Existing tools struggle to accurately annotate HLA and KIR genes in long-read assemblies.

Approach:

• Introduced Immuannot, a novel computational tool for annotating HLA and KIR gene structures and typing alleles.
• Applied Immuannot to 56 regional and 212 whole-genome assemblies.
• Successfully annotated 9,931 HLA and KIR genes.

Key Points:

• Identified 4,068 novel HLA and KIR gene sequences, representing 2,664 distinct alleles compared to the Immuno Polymorphism Database (IPD).
• Discovered 92 novel protein sequences resulting from non-synonymous variations in novel alleles.
• Demonstrated complex haplotype structures and reported linkage between HLA/KIR haplotypes and gene alleles.

Conclusions:

• Immuannot facilitates efficient annotation and typing of highly polymorphic immune genes.
• The tool accelerates the discovery of new HLA and KIR alleles and their variations.
• Enables future association studies linking HLA/KIR haplotypes to clinical outcomes.