Full-resolution HLA and KIR gene annotations for human genome assemblies.

Area of Science:

• Immunogenetics
• Genomics
• Bioinformatics

Background:

• Human leukocyte antigen (HLA) and killer cell immunoglobulin-like receptor (KIR) genes are crucial for immune function and disease association.
• Their high polymorphism and location in complex genomic regions challenge traditional sequencing and annotation methods.
• Existing tools struggle to accurately annotate HLA and KIR genes in long-read genome assemblies.

Purpose of the Study:

• To introduce Immuannot, a novel computational tool for annotating HLA and KIR gene structures and typing their alleles.
• To address the limitations of current methods in studying these highly variable immune genes.
• To facilitate the discovery and characterization of novel HLA and KIR alleles and haplotypes.

Main Methods:

• Development of Immuannot, a specialized bioinformatics tool for gene annotation and allele typing.
• Application of Immuannot to 56 regional and 212 whole-genome assemblies.
• Comparison of annotated sequences against the Immuno Polymorphism Database (IPD).

Main Results:

• Immuannot successfully annotated 9931 HLA and KIR genes across diverse assemblies.
• Nearly half of the annotated genes (4068) contained novel sequences compared to existing databases.
• These novel sequences represented 2664 distinct alleles, including 92 novel protein sequences due to nonsynonymous variations.
• Complex HLA and KIR haplotype structures and their linkage with gene alleles were elucidated.

Conclusions:

• Immuannot is an effective tool for annotating complex HLA and KIR gene regions, particularly in long-read assemblies.
• The study discovered a significant number of novel HLA and KIR alleles and protein sequences, expanding known genetic diversity.
• Immuannot is expected to accelerate the identification of new immune gene variants and facilitate future research linking HLA/KIR haplotypes to clinical outcomes.