Nanopore sequencing and the Shasta toolkit enable efficient de novo assembly of eleven human genomes

De novo assembly of a human genome using nanopore long-read sequences has been reported, but it used more than 150,000 CPU hours and weeks of wall-clock time. To enable rapid human genome assembly, we present Shasta, a de novo long-read assembler, and polishing algorithms named MarginPolish and HELEN. Using a single PromethION nanopore sequencer and our toolkit, we assembled 11 highly contiguous human genomes de novo in 9 d. We achieved roughly 63× coverage, 42-kb read N50 values and 6.5× coverage in reads >100 kb using three flow cells per sample. Shasta produced a complete haploid human genome assembly in under 6 h on a single commercial compute node. MarginPolish and HELEN polished haploid assemblies to…

• HH
  Howard Hughes Medical Institute
• WM
  W. M. Keck Foundation

  Award: DT06172015
• ON
  Oxford Nanopore Technologies

  Award: SC20130149
• NI
  National Institutes of Health

  Awards: U01HL137183, R01HG010485, 1U01HL137183, 5T32HG008345-04, 2U41HG007234, U41HG010972, U01HG010961, 5U54HG007990, R01HG010053
• NI
  National Institute of Standards and Technology
• NH
  National Heart, Lung, and Blood Institute

  Award: 1U01HL137183
• NH
  National Human Genome Research Institute

  Awards: R01HG010485, R01HG010329, U41HG010972, U01HG010961, U01HL137183, 5T32HG008345, 3U24HG009084-03S1, R01HG010053, 2U41HG007234, 5U54HG007990