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.

Even though the importance of epigenetics was first recognized in light of its role in tissue development, an increasing amount of evidence has shown that it also plays an important role in the development and progression of many common diseases. We discuss some recent findings on one representative epigenetic modification, DNA methylation, in some common diseases. While many new risk factors have been identified through the population-based epigenetic epidemiologic studies on the role of epigenetics in common diseases, this relatively new field still faces many unique challenges. Here, we describe those promises and unique challenges of epigenetic epidemiological studies and propose some potential solutions.