Semi-automated assembly of high-quality diploid human reference genomes
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Semi-automated assembly of high-quality diploid human reference genomes. / Jarvis, Erich D.; Formenti, Giulio; Rhie, Arang; Guarracino, Andrea; Yang, Chentao; Wood, Jonathan; Tracey, Alan; Thibaud-Nissen, Francoise; Vollger, Mitchell R.; Porubsky, David; Cheng, Haoyu; Asri, Mobin; Logsdon, Glennis A.; Carnevali, Paolo; Chaisson, Mark J.P.; Chin, Chen Shan; Cody, Sarah; Collins, Joanna; Ebert, Peter; Escalona, Merly; Fedrigo, Olivier; Fulton, Robert S.; Fulton, Lucinda L.; Garg, Shilpa; Gerton, Jennifer L.; Ghurye, Jay; Granat, Anastasiya; Green, Richard E.; Harvey, William; Hasenfeld, Patrick; Hastie, Alex; Haukness, Marina; Jaeger, Erich B.; Jain, Miten; Kirsche, Melanie; Kolmogorov, Mikhail; Korbel, Jan O.; Koren, Sergey; Korlach, Jonas; Lee, Joyce; Li, Daofeng; Lindsay, Tina; Lucas, Julian; Luo, Feng; Marschall, Tobias; Mitchell, Matthew W.; McDaniel, Jennifer; Nie, Fan; Zhang, Guojie; Li, Heng; Human Pangenome Reference Consortium.
In: Nature, Vol. 611, No. 7936, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Semi-automated assembly of high-quality diploid human reference genomes
AU - Jarvis, Erich D.
AU - Formenti, Giulio
AU - Rhie, Arang
AU - Guarracino, Andrea
AU - Yang, Chentao
AU - Wood, Jonathan
AU - Tracey, Alan
AU - Thibaud-Nissen, Francoise
AU - Vollger, Mitchell R.
AU - Porubsky, David
AU - Cheng, Haoyu
AU - Asri, Mobin
AU - Logsdon, Glennis A.
AU - Carnevali, Paolo
AU - Chaisson, Mark J.P.
AU - Chin, Chen Shan
AU - Cody, Sarah
AU - Collins, Joanna
AU - Ebert, Peter
AU - Escalona, Merly
AU - Fedrigo, Olivier
AU - Fulton, Robert S.
AU - Fulton, Lucinda L.
AU - Garg, Shilpa
AU - Gerton, Jennifer L.
AU - Ghurye, Jay
AU - Granat, Anastasiya
AU - Green, Richard E.
AU - Harvey, William
AU - Hasenfeld, Patrick
AU - Hastie, Alex
AU - Haukness, Marina
AU - Jaeger, Erich B.
AU - Jain, Miten
AU - Kirsche, Melanie
AU - Kolmogorov, Mikhail
AU - Korbel, Jan O.
AU - Koren, Sergey
AU - Korlach, Jonas
AU - Lee, Joyce
AU - Li, Daofeng
AU - Lindsay, Tina
AU - Lucas, Julian
AU - Luo, Feng
AU - Marschall, Tobias
AU - Mitchell, Matthew W.
AU - McDaniel, Jennifer
AU - Nie, Fan
AU - Zhang, Guojie
AU - Li, Heng
AU - Human Pangenome Reference Consortium
N1 - Publisher Copyright: © 2022, The Author(s).
PY - 2022
Y1 - 2022
N2 - The current human reference genome, GRCh38, represents over 20 years of effort to generate a high-quality assembly, which has benefitted society1,2. However, it still has many gaps and errors, and does not represent a biological genome as it is a blend of multiple individuals3,4. Recently, a high-quality telomere-to-telomere reference, CHM13, was generated with the latest long-read technologies, but it was derived from a hydatidiform mole cell line with a nearly homozygous genome5. To address these limitations, the Human Pangenome Reference Consortium formed with the goal of creating high-quality, cost-effective, diploid genome assemblies for a pangenome reference that represents human genetic diversity6. Here, in our first scientific report, we determined which combination of current genome sequencing and assembly approaches yield the most complete and accurate diploid genome assembly with minimal manual curation. Approaches that used highly accurate long reads and parent–child data with graph-based haplotype phasing during assembly outperformed those that did not. Developing a combination of the top-performing methods, we generated our first high-quality diploid reference assembly, containing only approximately four gaps per chromosome on average, with most chromosomes within ±1% of the length of CHM13. Nearly 48% of protein-coding genes have non-synonymous amino acid changes between haplotypes, and centromeric regions showed the highest diversity. Our findings serve as a foundation for assembling near-complete diploid human genomes at scale for a pangenome reference to capture global genetic variation from single nucleotides to structural rearrangements.
AB - The current human reference genome, GRCh38, represents over 20 years of effort to generate a high-quality assembly, which has benefitted society1,2. However, it still has many gaps and errors, and does not represent a biological genome as it is a blend of multiple individuals3,4. Recently, a high-quality telomere-to-telomere reference, CHM13, was generated with the latest long-read technologies, but it was derived from a hydatidiform mole cell line with a nearly homozygous genome5. To address these limitations, the Human Pangenome Reference Consortium formed with the goal of creating high-quality, cost-effective, diploid genome assemblies for a pangenome reference that represents human genetic diversity6. Here, in our first scientific report, we determined which combination of current genome sequencing and assembly approaches yield the most complete and accurate diploid genome assembly with minimal manual curation. Approaches that used highly accurate long reads and parent–child data with graph-based haplotype phasing during assembly outperformed those that did not. Developing a combination of the top-performing methods, we generated our first high-quality diploid reference assembly, containing only approximately four gaps per chromosome on average, with most chromosomes within ±1% of the length of CHM13. Nearly 48% of protein-coding genes have non-synonymous amino acid changes between haplotypes, and centromeric regions showed the highest diversity. Our findings serve as a foundation for assembling near-complete diploid human genomes at scale for a pangenome reference to capture global genetic variation from single nucleotides to structural rearrangements.
U2 - 10.1038/s41586-022-05325-5
DO - 10.1038/s41586-022-05325-5
M3 - Journal article
C2 - 36261518
AN - SCOPUS:85140231380
VL - 611
JO - Nature
JF - Nature
SN - 0028-0836
IS - 7936
ER -
ID: 330467025