PMID- 33288905
OWN - NLM
STAT- MEDLINE
DCOM- 20210414
LR  - 20210731
IS  - 1546-1696 (Electronic)
IS  - 1087-0156 (Print)
IS  - 1087-0156 (Linking)
VI  - 39
IP  - 3
DP  - 2021 Mar
TI  - Chromosome-scale, haplotype-resolved assembly of human genomes.
PG  - 309-312
LID - 10.1038/s41587-020-0711-0 [doi]
AB  - Haplotype-resolved or phased genome assembly provides a complete picture of 
      genomes and their complex genetic variations. However, current algorithms for 
      phased assembly either do not generate chromosome-scale phasing or require 
      pedigree information, which limits their application. We present a method named 
      diploid assembly (DipAsm) that uses long, accurate reads and long-range 
      conformation data for single individuals to generate a chromosome-scale phased 
      assembly within 1 day. Applied to four public human genomes, PGP1, HG002, NA12878 
      and HG00733, DipAsm produced haplotype-resolved assemblies with minimum contig 
      length needed to cover 50% of the known genome (NG50) up to 25 Mb and phased 
      ~99.5% of heterozygous sites at 98-99% accuracy, outperforming other approaches 
      in terms of both contiguity and phasing completeness. We demonstrate the 
      importance of chromosome-scale phased assemblies for the discovery of structural 
      variants (SVs), including thousands of new transposon insertions, and of highly 
      polymorphic and medically important regions such as the human leukocyte antigen 
      (HLA) and killer cell immunoglobulin-like receptor (KIR) regions. DipAsm will 
      facilitate high-quality precision medicine and studies of individual haplotype 
      variation and population diversity.
FAU - Garg, Shilpa
AU  - Garg S
AUID- ORCID: 0000-0003-0200-4200
AD  - Department of Genetics, Harvard Medical School, Boston, MA, USA. 
      shilpa_garg@hms.harvard.edu.
AD  - Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA. 
      shilpa_garg@hms.harvard.edu.
AD  - Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. 
      shilpa_garg@hms.harvard.edu.
FAU - Fungtammasan, Arkarachai
AU  - Fungtammasan A
AD  - DNAnexus, Mountain View, CA, USA.
FAU - Carroll, Andrew
AU  - Carroll A
AD  - Google, Mountain View, CA, USA.
FAU - Chou, Mike
AU  - Chou M
AD  - Department of Genetics, Harvard Medical School, Boston, MA, USA.
FAU - Schmitt, Anthony
AU  - Schmitt A
AD  - Arima Genomics, San Diego, CA, USA.
FAU - Zhou, Xiang
AU  - Zhou X
AD  - Arima Genomics, San Diego, CA, USA.
FAU - Mac, Stephen
AU  - Mac S
AD  - Arima Genomics, San Diego, CA, USA.
FAU - Peluso, Paul
AU  - Peluso P
AD  - Pacific Biosciences, Menlo Park, CA, USA.
FAU - Hatas, Emily
AU  - Hatas E
AD  - Pacific Biosciences, Menlo Park, CA, USA.
FAU - Ghurye, Jay
AU  - Ghurye J
AD  - Dovetail Genomics, Scotts Valley, CA, USA.
FAU - Maguire, Jared
AU  - Maguire J
AD  - Dovetail Genomics, Scotts Valley, CA, USA.
FAU - Mahmoud, Medhat
AU  - Mahmoud M
AUID- ORCID: 0000-0002-2553-4231
AD  - Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
FAU - Cheng, Haoyu
AU  - Cheng H
AD  - Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA.
AD  - Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
FAU - Heller, David
AU  - Heller D
AUID- ORCID: 0000-0001-8346-9565
AD  - Max Planck Institute for Molecular Genetics, Berlin, Germany.
FAU - Zook, Justin M
AU  - Zook JM
AUID- ORCID: 0000-0003-2309-8402
AD  - Material Measurement Laboratory, National Institute of Standards and Technology, 
      Gaithersburg, MD, USA.
FAU - Moemke, Tobias
AU  - Moemke T
AD  - Saarland University, Saarbrucken, Germany.
FAU - Marschall, Tobias
AU  - Marschall T
AUID- ORCID: 0000-0002-9376-1030
AD  - Saarland University, Saarbrucken, Germany.
AD  - Max Planck Institute for Informatics, Saarbrucken, Germany.
FAU - Sedlazeck, Fritz J
AU  - Sedlazeck FJ
AUID- ORCID: 0000-0001-6040-2691
AD  - Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
FAU - Aach, John
AU  - Aach J
AD  - Department of Genetics, Harvard Medical School, Boston, MA, USA.
FAU - Chin, Chen-Shan
AU  - Chin CS
AUID- ORCID: 0000-0003-4394-2455
AD  - DNAnexus, Mountain View, CA, USA. jchin@dnanexus.com.
FAU - Church, George M
AU  - Church GM
AUID- ORCID: 0000-0003-3535-2076
AD  - Department of Genetics, Harvard Medical School, Boston, MA, USA. 
      gchurch@genetics.med.harvard.edu.
FAU - Li, Heng
AU  - Li H
AUID- ORCID: 0000-0003-4874-2874
AD  - Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA. 
      hli@ds.dfci.harvard.edu.
AD  - Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. 
      hli@ds.dfci.harvard.edu.
LA  - eng
GR  - R01 HG010040/HG/NHGRI NIH HHS/United States
GR  - RM1 HG008525/HG/NHGRI NIH HHS/United States
GR  - U01 HG010971/HG/NHGRI NIH HHS/United States
GR  - K99 HG010906/HG/NHGRI NIH HHS/United States
GR  - UM1 HG008898/HG/NHGRI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20201207
PL  - United States
TA  - Nat Biotechnol
JT  - Nature biotechnology
JID - 9604648
SB  - IM
MH  - Algorithms
MH  - *Chromosomes, Human
MH  - *Genome, Human
MH  - *Haplotypes
MH  - Heterozygote
MH  - Humans
MH  - Polymorphism, Single Nucleotide
PMC - PMC7954703
MID - NIHMS1630556
COIS- F.J.S. obtained a Pacbio SMRT grant in 2019 and had multiple travels sponsored by 
      Pacific Biosciences and Oxford Nanopore Technologies. E.H. and P.P. are employees 
      of Pacific Biosciences. C.-S.C. and A.F. are employees of DNAnexus. A.S., X.Z. 
      and S.M. are employees of Arima Genomics. J.G. and J.M. are employees of Dovetail 
      Genomics. A.C. is an employee of Google. H.L. is a consultant of Integrated DNA 
      Technologies, Inc. and on the Scientific Advisory Boards of Sentieon, Inc., BGI 
      and OrigiMed. G.M.C. is a cofounder of Editas Medicine and has other financial 
      interests, listed at http://arep.med.harvard.edu/gmc/tech.html.
EDAT- 2020/12/09 06:00
MHDA- 2021/04/15 06:00
PMCR- 2020/12/07
CRDT- 2020/12/08 05:44
PHST- 2019/10/21 00:00 [received]
PHST- 2020/09/17 00:00 [accepted]
PHST- 2020/09/09 00:00 [revised]
PHST- 2020/12/09 06:00 [pubmed]
PHST- 2021/04/15 06:00 [medline]
PHST- 2020/12/08 05:44 [entrez]
PHST- 2020/12/07 00:00 [pmc-release]
AID - 10.1038/s41587-020-0711-0 [pii]
AID - 711 [pii]
AID - 10.1038/s41587-020-0711-0 [doi]
PST - ppublish
SO  - Nat Biotechnol. 2021 Mar;39(3):309-312. doi: 10.1038/s41587-020-0711-0. Epub 2020 
      Dec 7.