Biologically-informed Killer cell immunoglobulin-like receptor (KIR) gene annotation tool

Area of Science:

• Immunogenetics
• Computational Biology
• Genomics

Background:

• Natural Killer (NK) cells are crucial for innate immunity, with their function regulated by Killer cell Immunoglobulin-like Receptors (KIRs).
• Accurate KIR genotyping is vital for immunogenetic research, but the diversity and complexity of KIR genes pose significant challenges.
• Existing genotyping methods struggle with KIR gene variability, impacting accuracy, especially on high-quality phased genome assemblies.

Purpose of the Study:

• To introduce BAKIR, a computational tool specifically designed for accurate KIR genotyping and annotation on high-quality phased genome assemblies.
• To enhance the precision of KIR gene and allele identification by focusing on functional mutations.
• To improve the accuracy and relevance of KIR gene and allele calls in immunogenetic studies.

Main Methods:

• BAKIR employs a multi-stage process involving mapping, alignment, and variant calling tailored for KIR locus analysis.
• The tool is structured to identify key functional mutations, improving the identification of gene and allele variants.
• It ensures high precision in gene and allele identification while maintaining high recall for mutated or truncated sequences.

Main Results:

• BAKIR demonstrated improved annotations and identified novel variants when evaluated on a subset of Human Pangenome Reference Consortium (HPRC) assemblies.
• The tool successfully addresses challenges in KIR genotyping on complex, phased genome data.
• BAKIR enhances the accuracy of KIR gene and allele calls, contributing to more reliable immunogenetic research.

Conclusions:

• BAKIR is an effective computational solution for accurate KIR genotyping and annotation, particularly on challenging phased genome assemblies.
• The tool's ability to identify functional mutations and novel variants advances KIR-related immunogenetic research.
• BAKIR is freely available with user-friendly installation and command-line options, promoting widespread adoption in the scientific community.