The human leukocyte antigen (HLA) genes and the killer cell immunoglobulin-like receptor (KIR) genes are critical to immune responses and are associated with many immune-related diseases. Located in highly polymorphic regions, it is difficult to study them with traditional short-read alignment-based methods. Although modern long-read assemblers can often assemble these genes, using existing tools to annotate HLA and KIR genes in these assemblies remains a nontrivial task. Here, we describe Immuannot, a new computation tool to annotate the gene structures of HLA and KIR genes and to type the allele of each gene. Applying Immuannot to 56 regional and 212 whole-genome assemblies from previous studies, we annotate 9931 HLA and KIR genes and found that almost half of these genes, 4068, have novel sequences compared with the current Immuno Polymorphism Database (IPD). These novel gene sequences are represented by 2664 distinct alleles, some of which contained nonsynonymous variations, resulting in 92 novel protein sequences. We demonstrate the complex haplotype structures at the two loci and report the linkage between HLA/KIR haplotypes and gene alleles. We anticipate that Immuannot will speed up the discovery of new HLA/KIR alleles and enable the association of HLA/KIR haplotype structures with clinical outcomes in the future.

中文翻译：

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用于人类基因组组装的全分辨率 HLA 和 KIR 基因注释


人类白细胞抗原 （HLA） 基因和杀伤细胞免疫球蛋白样受体 （KIR） 基因对免疫反应至关重要，并与许多免疫相关疾病有关。位于高度多态性区域，很难用传统的基于短读长比对的方法研究它们。尽管现代长读长组装器通常可以组装这些基因，但使用现有工具注释这些组装中的 HLA 和 KIR 基因仍然是一项艰巨的任务。在这里，我们描述了 Immuannot，这是一种新的计算工具，用于注释 HLA 和 KIR 基因的基因结构并键入每个基因的等位基因。将 Immuannot 应用于先前研究的 56 个区域和 212 个全基因组组装，我们注释了 9931 个 HLA 和 KIR 基因，发现与当前的免疫多态性数据库 （IPD） 相比，这些基因中几乎有一半 （4068） 具有新序列。这些新的基因序列由 2664 个不同的等位基因表示，其中一些包含非同义变异，从而产生 92 个新的蛋白质序列。我们展示了两个基因座的复杂单倍型结构，并报道了 HLA/KIR 单倍型和基因等位基因之间的联系。我们预计 Immuannot 将加速发现新的 HLA/KIR 等位基因，并在未来实现 HLA/KIR 单倍型结构与临床结果的关联。