Chromosome-scale, haplotype-resolved assembly of human genomes

Research output: Contribution to journal › Journal article › Research › peer-review

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Chromosome-scale, haplotype-resolved assembly of human genomes. / Garg, Shilpa; Fungtammasan, Arkarachai; Carroll, Andrew; Chou, Mike; Schmitt, Anthony; Zhou, Xiang; Mac, Stephen; Peluso, Paul; Hatas, Emily; Ghurye, Jay; Maguire, Jared; Mahmoud, Medhat; Cheng, Haoyu; Heller, David; Zook, Justin M.; Moemke, Tobias; Marschall, Tobias; Sedlazeck, Fritz J.; Aach, John; Chin, Chen-Shan; Church, George M.; Li, Heng.

In: Nature Biotechnology, 07.12.2020.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Garg, S, Fungtammasan, A, Carroll, A, Chou, M, Schmitt, A, Zhou, X, Mac, S, Peluso, P, Hatas, E, Ghurye, J, Maguire, J, Mahmoud, M, Cheng, H, Heller, D, Zook, JM, Moemke, T, Marschall, T, Sedlazeck, FJ, Aach, J, Chin, C-S, Church, GM & Li, H 2020, 'Chromosome-scale, haplotype-resolved assembly of human genomes', Nature Biotechnology. https://doi.org/10.1038/s41587-020-0711-0

APA

Garg, S., Fungtammasan, A., Carroll, A., Chou, M., Schmitt, A., Zhou, X., Mac, S., Peluso, P., Hatas, E., Ghurye, J., Maguire, J., Mahmoud, M., Cheng, H., Heller, D., Zook, J. M., Moemke, T., Marschall, T., Sedlazeck, F. J., Aach, J., ... Li, H. (2020). Chromosome-scale, haplotype-resolved assembly of human genomes. Nature Biotechnology. https://doi.org/10.1038/s41587-020-0711-0

Vancouver

Garg S, Fungtammasan A, Carroll A, Chou M, Schmitt A, Zhou X et al. Chromosome-scale, haplotype-resolved assembly of human genomes. Nature Biotechnology. 2020 Dec 7. https://doi.org/10.1038/s41587-020-0711-0

Author

Garg, Shilpa ; Fungtammasan, Arkarachai ; Carroll, Andrew ; Chou, Mike ; Schmitt, Anthony ; Zhou, Xiang ; Mac, Stephen ; Peluso, Paul ; Hatas, Emily ; Ghurye, Jay ; Maguire, Jared ; Mahmoud, Medhat ; Cheng, Haoyu ; Heller, David ; Zook, Justin M. ; Moemke, Tobias ; Marschall, Tobias ; Sedlazeck, Fritz J. ; Aach, John ; Chin, Chen-Shan ; Church, George M. ; Li, Heng. / Chromosome-scale, haplotype-resolved assembly of human genomes. In: Nature Biotechnology. 2020.

Bibtex

@article{dc42c468fe124b0d9c4a386f65aba311,
title = "Chromosome-scale, haplotype-resolved assembly of human genomes",
abstract = "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.",
author = "Shilpa Garg and Arkarachai Fungtammasan and Andrew Carroll and Mike Chou and Anthony Schmitt and Xiang Zhou and Stephen Mac and Paul Peluso and Emily Hatas and Jay Ghurye and Jared Maguire and Medhat Mahmoud and Haoyu Cheng and David Heller and Zook, {Justin M.} and Tobias Moemke and Tobias Marschall and Sedlazeck, {Fritz J.} and John Aach and Chen-Shan Chin and Church, {George M.} and Heng Li",
year = "2020",
month = dec,
day = "7",
doi = "10.1038/s41587-020-0711-0",
language = "English",
journal = "Nature Biotechnology",
issn = "1087-0156",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Chromosome-scale, haplotype-resolved assembly of human genomes

AU - Garg, Shilpa

AU - Fungtammasan, Arkarachai

AU - Carroll, Andrew

AU - Chou, Mike

AU - Schmitt, Anthony

AU - Zhou, Xiang

AU - Mac, Stephen

AU - Peluso, Paul

AU - Hatas, Emily

AU - Ghurye, Jay

AU - Maguire, Jared

AU - Mahmoud, Medhat

AU - Cheng, Haoyu

AU - Heller, David

AU - Zook, Justin M.

AU - Moemke, Tobias

AU - Marschall, Tobias

AU - Sedlazeck, Fritz J.

AU - Aach, John

AU - Chin, Chen-Shan

AU - Church, George M.

AU - Li, Heng

PY - 2020/12/7

Y1 - 2020/12/7

N2 - 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.

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.

U2 - 10.1038/s41587-020-0711-0

DO - 10.1038/s41587-020-0711-0

M3 - Journal article

C2 - 33288905

JO - Nature Biotechnology

JF - Nature Biotechnology

SN - 1087-0156

ER -

ID: 255785031