The complete diploid reference genome of RPE-1 identifies human phased epigenetic landscapes

Area of Science:

• Genomics
• Cell Biology
• Bioinformatics

Background:

• Human reference genomes exhibit sequence divergence, particularly at polymorphic loci like centromeres.
• This divergence questions the accuracy of using general human references for analyzing experimental cell line sequencing data.
• RPE-1 cells are widely used, stable laboratory cell lines critical for various biological studies.

Approach:

• Generated a complete diploid genome assembly (RPE1v1.0) for the human retinal epithelial (RPE-1) cell line.
• The assembly features phased haplotypes and chromosome-level scaffolds with high base accuracy, spanning centromeres.
• Mapped cell-line-specific genomic variations, including a novel translocation t(Xq;10q) and a chromosome 10 duplication.

Key Points:

• The RPE1v1.0 assembly provides a matched reference, enhancing multi-omics read mapping quality for RPE-1 cells.
• Significant reduction in alignment mismatches was observed compared to using the CHM13 human reference genome.
• Identified kinetochore sites at base-pair resolution and revealed substantial haplotype-specific genetic and epigenetic variations.

Conclusions:

• Matched reference genomes are crucial for accurate multi-omics data analysis in experimental cell lines.
• This study highlights the utility of comprehensive cell line assemblies for uncovering detailed genomic and epigenomic variation.
• Advocates for the assembly of experimentally relevant cell lines to serve as standardized references for broader research applications.