kir-mapper: A Toolkit for Killer-Cell Immunoglobulin-Like Receptor (KIR) Genotyping From Short-Read Second-Generation...

Area of Science:

• Immunogenetics
• Bioinformatics
• Genomics

Background:

• Killer cell immunoglobulin-like receptors (KIRs) are crucial for natural killer (NK) cell function.
• Genotyping KIR genes from short-read sequencing data is difficult due to high gene similarity and polymorphism.
• Existing bioinformatics tools like PING and T1K show discordant results and lack genome context for SNPs.

Purpose of the Study:

• To develop a novel bioinformatics toolkit, kir-mapper, for accurate KIR gene analysis from short-read sequencing data.
• To enable detection of KIR alleles, copy number variations, SNPs, and InDels in the context of the hg38 reference genome.
• To improve KIR genotyping accuracy and suitability for whole-genome association studies.

Main Methods:

• Development of the kir-mapper toolkit for analyzing KIR genes from whole-genome sequencing (WGS), whole-exome sequencing (WES), and capture-based data.
• Implementation of strategies for phasing SNPs and InDels within and across genes to reduce ambiguity.
• Systematic comparison of kir-mapper with existing tools (PING, T1K) using diverse sequencing data and long-read data as a truth set.

Main Results:

• kir-mapper demonstrated higher accuracy in KIR genotyping from WGS data compared to PING and T1K, validated by long-read sequencing.
• For WES data, kir-mapper showed improved accuracy over T1K for highly polymorphic genes like KIR3DL3 and KIR3DL2.
• The toolkit successfully identified KIR alleles, copy number variations, and SNPs/InDels in the hg38 reference genome context.

Conclusions:

• kir-mapper provides a more accurate and context-aware approach for KIR gene analysis from short-read sequencing data.
• The choice of genotyping tool should consider the data type (WGS, WES) and specific genes of interest.
• kir-mapper enhances the utility of KIR genotyping for immunogenetic and association studies.