Biologically-informed killer cell immunoglobulin-like receptor gene annotation tool

Area of Science:

• Immunogenetics
• Computational Biology
• Genomics

Background:

• Natural killer (NK) cells are vital for innate immunity, regulated by Killer cell Immunoglobulin-like Receptors (KIRs).
• KIR gene diversity and complexity challenge accurate genotyping, hindering immunogenetic research and understanding of NK cell functions in health and disease.
• High-quality phased genome assemblies, like those from the Human Pangenome Consortium, require specialized tools for precise KIR annotation.

Purpose of the Study:

• To introduce BAKIR (Biologically informed Annotator for KIR locus), a computational tool designed for accurate KIR genotyping and annotation.
• To address the limitations of traditional methods in handling variable KIR gene structures on phased genome assemblies.
• To improve the identification and relevance of KIR gene and allele calls by focusing on functional mutations.

Main Methods:

• BAKIR employs a multi-stage process involving mapping, alignment, and variant calling.
• The tool is structured to identify key functional mutations for enhanced annotation accuracy.
• It ensures high precision in gene and allele identification while maintaining recall for mutated or truncated sequences.

Main Results:

• BAKIR demonstrated improved annotations and identified novel variants on Human Pangenome Reference Consortium (HPRC) assemblies.
• The tool enhances the accuracy of KIR gene and allele calls, even for complex or divergent sequences.
• Evaluation on HPRC data confirmed BAKIR's ability to refine existing annotations and discover new genetic variations.

Conclusions:

• BAKIR is a novel computational tool that overcomes challenges in KIR genotyping and annotation on high-quality genome assemblies.
• Its biologically informed approach improves the accuracy and relevance of KIR gene and allele identification.
• Freely available on GitHub with multiple installation options and a user-friendly interface, BAKIR promotes wider adoption in immunogenetic research.