RT Journal Article
SR Electronic
T1 Evaluation of GRCh38 and de novo haploid genome assemblies demonstrates the enduring quality of the reference assembly
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 072116
DO 10.1101/072116
A1 Valerie A. Schneider
A1 Tina Graves-Lindsay
A1 Kerstin Howe
A1 Nathan Bouk
A1 Hsiu-Chuan Chen
A1 Paul A. Kitts
A1 Terence D. Murphy
A1 Kim D. Pruitt
A1 Françoise Thibaud-Nissen
A1 Derek Albracht
A1 Robert S. Fulton
A1 Milinn Kremitzki
A1 Vince Magrini
A1 Chris Markovic
A1 Sean McGrath
A1 Karyn Meltz Steinberg
A1 Kate Auger
A1 Will Chow
A1 Joanna Collins
A1 Glenn Harden
A1 Tim Hubbard
A1 Sarah Pelan
A1 Jared T. Simpson
A1 Glen Threadgold
A1 James Torrance
A1 Jonathan Wood
A1 Laura Clarke
A1 Sergey Koren
A1 Matthew Boitano
A1 Heng Li
A1 Chen-Shan Chin
A1 Adam M. Phillippy
A1 Richard Durbin
A1 Richard K. Wilson
A1 Paul Flicek
A1 Deanna M. Church
YR 2016
UL http://biorxiv.org/content/early/2016/08/30/072116.abstract
AB 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 and 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 centromeres. We also expanded the number of alternate loci to create a reference that provides a more robust representation of human population variation. We demonstrate that the updates render the reference an improved annotation substrate, alter read alignments in unchanged regions and impact variant interpretation at clinically relevant loci. We additionally evaluated a collection of new de novo long-read haploid assemblies and conclude that while the new assemblies compare favorably to the reference with respect to continuity, error rate, and gene completeness, the reference still provides the best representation for complex genomic regions and coding sequences. We assert that the collected updates in GRCh38 make the newer assembly a more robust substrate for comprehensive analyses that will promote our understanding of human biology and advance our efforts to improve health.