RT Journal
A1 Schneider, Valerie A.
A1 Graves-Lindsay, Tina
A1 Howe, Kerstin
A1 Bouk, Nathan
A1 Chen, Hsiu-Chuan
A1 Kitts, Paul A.
A1 Murphy, Terence D.
A1 Pruitt, Kim D.
A1 Thibaud-Nissen, Françoise
A1 Albracht, Derek
A1 Fulton, Robert S.
A1 Kremitzki, Milinn
A1 Magrini, Vincent
A1 Markovic, Chris
A1 McGrath, Sean
A1 Steinberg, Karyn Meltz
A1 Auger, Kate
A1 Chow, William
A1 Collins, Joanna
A1 Harden, Glenn
A1 Hubbard, Timothy
A1 Pelan, Sarah
A1 Simpson, Jared T.
A1 Threadgold, Glen
A1 Torrance, James
A1 Wood, Jonathan M.
A1 Clarke, Laura
A1 Koren, Sergey
A1 Boitano, Matthew
A1 Peluso, Paul
A1 Li, Heng
A1 Chin, Chen-Shan
A1 Phillippy, Adam M.
A1 Durbin, Richard
A1 Wilson, Richard K.
A1 Flicek, Paul
A1 Eichler, Evan E.
A1 Church, Deanna M.
T1 Evaluation of GRCh38 and de novo haploid genome assemblies demonstrates the enduring quality of the reference assembly
JF Genome Research 
JO Genome Research 
YR 2017 
FD May 01 
VO 27 
IS 5 
SP 849 
OP 864 
DO 10.1101/gr.213611.116 
UL http://genome.cshlp.org/content/27/5/849.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; 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 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 although 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.