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

## TL;DR

This paper creates detailed genetic maps of the MHC region in five common cancer cell lines to improve understanding of immune-related genes and cancer biology.

## Contribution

The study provides high-quality, haplotype-resolved MHC assemblies for five widely used tumor cell lines.

## Key findings

- CRISPR-based enrichment and long-read sequencing enabled accurate MHC haplotype assembly.
- Aneuploidy in the MHC region was characterized using the assembled haplotypes.
- The resource enhances interpretation of genomic and epigenomic data in cancer research.

## 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.