Killer cell immunoglobulin like receptor (KIR) genes and human leukocyte antigen (HLA) genes play important roles in innate and adaptive immunity. They are highly polymorphic and cannot be genotyped with standard variant calling pipelines. Compared with HLA genes, many KIR genes are similar to each other in sequences and may be absent in the chromosomes. Therefore, although many tools have been developed to genotype HLA genes using common sequencing data, none of them work for KIR genes. Even specialized KIR genotypers could not resolve all the KIR genes. Here we describe T1K, a novel computational method for the efficient and accurate inference of KIR or HLA alleles from RNA-seq, whole-genome sequencing, or whole-exome sequencing data. T1K jointly considers alleles across all genotyped genes, so it can reliably identify present genes and distinguish homologous genes, including the challenging KIR2DL5A/KIR2DL5B genes. This model also benefits HLA genotyping, where T1K achieves high accuracy in benchmarks. Moreover, T1K can call novel single-nucleotide variants and process single-cell data. Applying T1K to tumor single-cell RNA-seq data, we found that KIR2DL4 expression was enriched in tumor-specific CD8⁺ T cells. T1K may open the opportunity for HLA and KIR genotyping across various sequencing applications.

中文翻译：

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利用大规模并行测序数据进行高效、准确的 KIR 和 HLA 基因分型

杀伤细胞免疫球蛋白样受体（KIR）基因和人类白细胞抗原（HLA）基因在先天性和适应性免疫中发挥重要作用。它们具有高度多态性，无法使用标准变体检测管道进行基因分型。与HLA基因相比，许多KIR基因在序列上彼此相似并且可能不存在于染色体中。因此，尽管已经开发了许多工具来使用通用测序数据对 HLA 基因进行基因分型，但没有一个工具适用于 KIR 基因。即使专门的 KIR 基因分型仪也无法解析所有 KIR 基因。在这里，我们描述了 T1K，一种新颖的计算方法，用于从 RNA-seq、全基因组测序或全外显子组测序数据中高效、准确地推断 KIR 或 HLA 等位基因。T1K 共同考虑所有基因分型基因的等位基因，KIR2DL5A / KIR2DL5B基因。该模型也有利于 HLA 基因分型，其中 T1K 在基准测试中实现了高精度。此外，T1K 可以调用新的单核苷酸变体并处理单细胞数据。将 T1K 应用到肿瘤单细胞 RNA-seq 数据中，我们发现KIR2DL4表达在肿瘤特异性 CD8 ⁺ T 细胞中富集。T1K 可能为跨各种测序应用的 HLA 和 KIR 基因分型提供机会。