Motivation

Recent advances in long-read sequencing technologies led to rapid progress in centromere assembly in the last year and, for the first time, opened a possibility to address the long-standing questions about the architecture and evolution of human centromeres. However, since these advances have not been yet accompanied by the development of the centromere-specific bioinformatics algorithms, even the fundamental questions (e.g. centromere annotation by deriving the complete set of human monomers and high-order repeats), let alone more complex questions (e.g. explaining how monomers and high-order repeats evolved) about human centromeres remain open. Moreover, even though there was a four-decade-long series of studies aimed at cataloging all human monomers and high-order repeats, the rigorous algorithmic definitions of these concepts are still lacking. Thus, the development of a centromere annotation tool is a prerequisite for follow-up personalized biomedical studies of centromeres across the human population and evolutionary studies of centromeres across various species.

Results

We describe the CentromereArchitect, the first tool for the centromere annotation in a newly sequenced genome, apply it to the recently generated complete assembly of a human genome by the Telomere-to-Telomere consortium, generate the complete set of human monomers and high-order repeats for ‘live’ centromeres, and reveal a vast set of hybrid monomers that may represent the focal points of centromere evolution.

Availability and implementation

CentromereArchitect is publicly available on https://github.com/ablab/stringdecomposer/tree/ismb2021

Supplementary information

Supplementary data are available at Bioinformatics online.

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