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

• DOI: 10.1101/gr.213611.116
• Publication Date: 2017-04-11T00:25:19Z
• Authors: Valerie A. Schneider; Tina Graves-Lindsay; Kerstin Howe; Nathan Bouk; Hsiu-Chuan Chen; Paul A. Kitts; Terence D. Murphy; Kim D. Pruitt; Françoise Thibaud...; Derek Albracht; Robert S. Fulton; Milinn Kremitzki; Vincent Magrini; Chris Markovic; Sean McGrath; Karyn Meltz Stein...; Kate Auger; William Chow; Joanna Collins; Glenn Harden; Timothy Hubbard; Sarah Pelan; Jared T. Simpson; Glen Threadgold; James Torrance; Jonathan M. Wood; Laura Clarke; Sergey Koren; Matthew Boitano; Paul Peluso; Heng Li; Chen-Shan Chin; Adam M. Phillippy; Richard Durbin; Richard K. Wilson; Paul Flicek; Evan E. Eichler; Deanna M. Church
• Keywords: Sequence 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 update since 2009; it reflects resolution roughly 1000 issues encompasses modifications ranging from thousands single base changes to megabase-scale path reorganizations, gap closures, localization previously orphaned sequences. We developed new approach sequence generation for targeted updates used data mapping technologies haplotype resources identify resolve larger issues. For time, contains sequence-based representations centromeres. also expanded number alternate loci create that provides more robust representation population variation. demonstrate render an improved annotation substrate, alter read alignments unchanged regions, impact variant interpretation at clinically relevant loci. additionally evaluated collection de novo long-read haploid assemblies conclude although compare favorably with respect continuity, error rate, gene completeness, still best complex genomic regions coding assert collected make newer substrate comprehensive analyses will promote our understanding biology advance efforts improve health.