Haplotype-resolved assemblies of the MHC region in five widely used tumor cell lines

IF 6.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases Pub Date : 2025-03-18 DOI:10.1016/j.gendis.2025.101603

Haozhe Yuan , Mengping Jiang , Xingyu Xu , Jialiang Zhu , Shulong Dong , Weida Meng , Dandan Zhang , Jiakang Ma , Yicheng Lin , Ziqiang Chen , Shaoyang Sun , Wenqing Qiu , Yun Liu

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引用次数: 0

Abstract

The major histocompatibility complex (MHC) region plays a crucial role in immune function and is implicated in various diseases and cancer immunoediting. However, its high polymorphism poses challenges for accurate genetic profiling using conventional reference genomes. Here, we present high-quality, haplotype-resolved assemblies of the MHC region in five widely used tumor cell lines: A549, HeLa, HepG2, K562, and U2OS. Numerous oncological studies extensively employ these cell lines, ranging from basic molecular research to drug discovery and personalized medicine approaches. By integrating CRISPR-based targeted enrichment with 10 × Genomics linked-read and PacBio HiFi long-read sequencing, we constructed MHC haplotypes for each cell line, providing a valuable resource for the research community. Using these assembled haplotypes as references, we characterize the aneuploidy of the MHC region in these cell lines, offering insights into the genetic landscape of this critical immunological locus. Our work addresses the urgent need for accurate MHC profiling in these widely used cell line models, enabling more precise interpretation of existing and future genomic and epigenomic data. This resource is expected to significantly enhance our understanding of tumor biology, immune responses, and the development of targeted therapies.

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五种广泛应用的肿瘤细胞系中MHC区域的单倍型分解组装

主要组织相容性复合体（MHC）区域在免疫功能中起着至关重要的作用，并与各种疾病和癌症的免疫编辑有关。然而，它的高多态性给传统参考基因组的精确遗传图谱带来了挑战。在这里，我们展示了五种广泛使用的肿瘤细胞系：A549， HeLa, HepG2， K562和U2OS的高质量，单倍型分解的MHC区域组装。许多肿瘤学研究广泛使用这些细胞系，从基础分子研究到药物发现和个性化医疗方法。通过将基于crispr的靶向富集与10 × Genomics linked-read和PacBio HiFi long-read测序相结合，我们构建了每个细胞系的MHC单倍型，为研究界提供了宝贵的资源。利用这些组装的单倍型作为参考，我们表征了这些细胞系中MHC区域的非整倍性，为这一关键免疫位点的遗传景观提供了见解。我们的工作解决了在这些广泛使用的细胞系模型中精确的MHC分析的迫切需要，从而能够更精确地解释现有和未来的基因组和表观基因组数据。这一资源有望显著提高我们对肿瘤生物学、免疫反应和靶向治疗发展的理解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Genes & Diseases Multiple-

CiteScore

7.30

自引率

0.00%

发文量

347

审稿时长

49 days

期刊介绍： Genes & Diseases is an international journal for molecular and translational medicine. The journal primarily focuses on publishing investigations on the molecular bases and experimental therapeutics of human diseases. Publication formats include full length research article, review article, short communication, correspondence, perspectives, commentary, views on news, and research watch. Aims and Scopes Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis will be placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.