Cell line-matched reference enables high-precision functional genomics.

ABSTRACT: Comparative analyses of newly available human genome assemblies highlight extensive variation that peaks at centromeres. Reliance on a single generic reference genome can thus hinder whole-genome analysis of sequencing data derived from laboratory cell lines and limit their accurate genomic manipulation. Here, we demonstrate that using an "isogenomic" diploid reference genome  - specific for the experimental cell line - substantially improves the accuracy of genomic, epigenomic, transcriptomic analyses and genome editing compared to a non-matched reference. Using our recently generated reference genome of the widely used diploid human cell line RPE-1, we uncover haplotype-specific genetic and epigenetic divergence across all centromeres. Mapping quality of RPE-1 data - DNA- and RNA-seq rea

SUBMITTER: Corda L 

PROVIDER: S-EPMC12711918 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature