Evaluation of GRCh38 and de novo haploid genome assemblies demonstrates the enduring quality of the reference assembly

The human reference genome assembly plays a central role in nearly all aspects of today's basic and clinical research. GRCh38 is the first coordinate-changing assembly update since 2009; it reflects the resolution of roughly 1000 issues and encompasses modifications ranging from thousands of single base changes to megabase-scale path reorganizations, gap closures, and localization of previously orphaned sequences. We developed a new approach to sequence generation for targeted base updates and used data from new genome mapping technologies and single haplotype resources to identify and resolve larger assembly issues. For the first time, the reference assembly contains sequence-based representations for the…

• HH
  Howard Hughes Medical Institute
• W
  Wellcome

  Awards: WT098051, WT095908, WT104947/Z/14/Z
• WT
  Wellcome Trust

  Awards: WT095908, WT104947/Z/14/Z, WT098051
• EM
  European Molecular Biology Laboratory
• NI
  National Institutes of Health

  Awards: 5U54HG003079, HG002385, 5U41HG007635, HG007635
• NH
  National Human Genome Research Institute

  Award: 5U54HG003079
• UN
  U.S. National Library of Medicine