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Chasing perfection: validation and polishing strategies for telomere-to-telomere genome assemblies

Published

Author(s)

Ann Mc Cartney, Kishwar Shafin, Michael Alonge, Justin Zook, Adam Phillippy, Arang Rhie

Abstract

Advances in long-read sequencing technologies and genome assembly methods have enabled the recent completion of the first telomere-to-telomere human genome assembly, which resolves complex segmental duplications and large tandem repeats, including centromeric satellite arrays in a complete hydatidiform mole (CHM13). Although derived from highly accurate sequences, evaluation revealed evidence of small errors and structural misassemblies in the initial draft assembly. To correct these errors, we designed a new repeat-aware polishing strategy that made accurate assembly corrections in large repeats without overcorrection, ultimately fixing 51% of the existing errors and improving the assembly quality value from 70.2 to 73.9 measured from PacBio high-fidelity and Illumina k-mers. By comparing our results to standard automated polishing tools, we outline common polishing errors and offer practical suggestions for genome projects with limited resources. We also show how sequencing biases in both high-fidelity and Oxford Nanopore Technologies reads cause signature assembly errors that can be corrected with a diverse panel of sequencing technologies.
Citation
Nature Methods
Volume
19

Keywords

human genome sequencing, polishing, reference genome, genome assembly

Citation

Mc Cartney, A. , Shafin, K. , Alonge, M. , Zook, J. , Phillippy, A. and Rhie, A. (2022), Chasing perfection: validation and polishing strategies for telomere-to-telomere genome assemblies, Nature Methods, [online], https://doi.org/10.1038/s41592-022-01440-3, https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=932846 (Accessed March 1, 2024)
Created March 31, 2022, Updated November 29, 2022