EasyCen: A Lightweight Framework for Centromere Localisation and Repeat-Organisation Profiling in Telomere-to-Telomere Genomes

Abstract

Accurate identification of centromeres in telomere-to-telomere (T2T) genomes remains difficult due to the rapid evolution of centromeric repeats and their lack of conserved sequence features. In this study, we present EasyCen, a lightweight sequence-based framework for centromere identification and repeat-architecture profiling across various eukaryotes. Rather than relying on repeat annotation or homology, EasyCen recognises centromeres based on recurrent positional features of repetitive DNA. Besides centromere localisation, EasyCen incorporates a repeat-pair profiling module for exploratory characterisation of internal repeat organisation. Benchmarking on Arabidopsis thaliana and Mus musculus showed high accuracy (typically > 85% coordinate overlap with published annotations) and substantially reduced runtime. Cross-species analysis revealed a ‘beads-on-a-string’-like repeat pattern in both mouse and human centromeres, associated with GC- and CpG-rich subdomains. EasyCen performs effectively without pre-existing repeat libraries, making it particularly useful for large, repeat-rich, or non-model genomes. Our analyses further suggest that certain organisational features of centromeric repeats may recur across diverse eukaryotic lineages despite rapid sequence turnover.