• Ann M. Mc Cartney
  • Kishwar Shafin
  • Michael Alonge
  • Andrey V. Bzikadze
  • Giulio Formenti
  • Arkarachai Fungtammasan
  • Kerstin Howe
  • Chirag Jain
  • Sergey Koren
  • Glennis A. Logsdon
  • Karen H. Miga
  • Alla Mikheenko
  • Benedict Paten
  • Alaina Shumate
  • Daniela C. Soto
  • Ivan Sović
  • Jonathan M.D. Wood
  • Justin M. Zook
  • Adam M. Phillippy
  • Arang Rhie

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.

Original languageEnglish
Pages (from-to)687-695
Number of pages9
JournalNature Methods
Volume19
Issue number6
Early online date1 Apr 2022
DOIs
StatePublished - Jun 2022

    Research areas

  • Female, Genome, Human, High-Throughput Nucleotide Sequencing/methods, Humans, Nanopores, Pregnancy, Sequence Analysis, DNA/methods, Telomere/genetics

    Scopus subject areas

  • Molecular Biology
  • Biochemistry
  • Biotechnology
  • Cell Biology

ID: 94683479