De novo assembly of a haplotype-resolved human genome

Hongzhi Cao; Honglong Wu; Ruibang Luo; Shujia Huang; Yuhui Sun; Xin Tong; Yinlong Xie; Binghang Liu; Hailong Yang; Hancheng Zheng; Jian Li; Bo Li; Yu Wang; Fang Yang; Peng Sun; Siyang Liu; Peng Gao; Haodong Huang; Jing Sun; Dan Chen; Guangzhu He; Weihua Huang; Zheng Huang; Yue Li; Laurent C.A.M. Tellier; Xiao Liu; Qiang Feng; Xun Xu; Xiuqing Zhang; Lars Bolund; Anders Krogh; Karsten Kristiansen; Radoje Drmanac; Snezana Drmanac; Rasmus Nielsen; Songgang Li; Jian Wang; Huanming Yang; Yingrui Li; Gane Ka-Shu Wong; Jun Wang

doi:10.1038/nbt.3200

De novo assembly of a haplotype-resolved human genome

Hongzhi Cao, Honglong Wu, Ruibang Luo, Shujia Huang, Yuhui Sun, Xin Tong, Yinlong Xie, Binghang Liu, Hailong Yang, Hancheng Zheng, Jian Li, Bo Li, Yu Wang, Fang Yang, Peng Sun, Siyang Liu, Peng Gao, Haodong Huang, Jing Sun, Dan ChenGuangzhu He, Weihua Huang, Zheng Huang, Yue Li, Laurent C.A.M. Tellier, Xiao Liu, Qiang Feng, Xun Xu, Xiuqing Zhang, Lars Bolund, Anders Krogh, Karsten Kristiansen, Radoje Drmanac, Snezana Drmanac, Rasmus Nielsen, Songgang Li, Jian Wang, Huanming Yang, Yingrui Li, Gane Ka-Shu Wong, Jun Wang

41 Citations (Scopus)

Abstract

The human genome is diploid, and knowledge of the variants on each chromosome is important for the interpretation of genomic information. Here we report the assembly of a haplotype-resolved diploid genome without using a reference genome. Our pipeline relies on fosmid pooling together with whole-genome shotgun strategies, based solely on next-generation sequencing and hierarchical assembly methods. We applied our sequencing method to the genome of an Asian individual and generated a 5.15-Gb assembled genome with a haplotype N50 of 484 kb. Our analysis identified previously undetected indels and 7.49 Mb of novel coding sequences that could not be aligned to the human reference genome, which include at least six predicted genes. This haplotype-resolved genome represents the most complete de novo human genome assembly to date. Application of our approach to identify individual haplotype differences should aid in translating genotypes to phenotypes for the development of personalized medicine.

Original language	English
Journal	Nature Biotechnology
Volume	33
Issue number	6
Pages (from-to)	617-626
Number of pages	10
ISSN	1087-0156
DOIs	https://doi.org/10.1038/nbt.3200
Publication status	Published - 11 Jun 2015

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Cao, H, Wu, H, Luo, R, Huang, S, Sun, Y, Tong, X, Xie, Y, Liu, B, Yang, H, Zheng, H, Li, J, Li, B, Wang, Y, Yang, F, Sun, P, Liu, S, Gao, P, Huang, H, Sun, J, Chen, D, He, G, Huang, W, Huang, Z, Li, Y, Tellier, LCAM, Liu, X, Feng, Q, Xu, X, Zhang, X, Bolund, L, Krogh, A , Kristiansen, K, Drmanac, R, Drmanac, S, Nielsen, R, Li, S, Wang, J, Yang, H, Li, Y, Wong, GK-S & Wang, J 2015, 'De novo assembly of a haplotype-resolved human genome', Nature Biotechnology, vol. 33, no. 6, pp. 617-626. https://doi.org/10.1038/nbt.3200

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abstract = "The human genome is diploid, and knowledge of the variants on each chromosome is important for the interpretation of genomic information. Here we report the assembly of a haplotype-resolved diploid genome without using a reference genome. Our pipeline relies on fosmid pooling together with whole-genome shotgun strategies, based solely on next-generation sequencing and hierarchical assembly methods. We applied our sequencing method to the genome of an Asian individual and generated a 5.15-Gb assembled genome with a haplotype N50 of 484 kb. Our analysis identified previously undetected indels and 7.49 Mb of novel coding sequences that could not be aligned to the human reference genome, which include at least six predicted genes. This haplotype-resolved genome represents the most complete de novo human genome assembly to date. Application of our approach to identify individual haplotype differences should aid in translating genotypes to phenotypes for the development of personalized medicine.",

author = "Hongzhi Cao and Honglong Wu and Ruibang Luo and Shujia Huang and Yuhui Sun and Xin Tong and Yinlong Xie and Binghang Liu and Hailong Yang and Hancheng Zheng and Jian Li and Bo Li and Yu Wang and Fang Yang and Peng Sun and Siyang Liu and Peng Gao and Haodong Huang and Jing Sun and Dan Chen and Guangzhu He and Weihua Huang and Zheng Huang and Yue Li and Tellier, {Laurent C.A.M.} and Xiao Liu and Qiang Feng and Xun Xu and Xiuqing Zhang and Lars Bolund and Anders Krogh and Karsten Kristiansen and Radoje Drmanac and Snezana Drmanac and Rasmus Nielsen and Songgang Li and Jian Wang and Huanming Yang and Yingrui Li and Wong, {Gane Ka-Shu} and Jun Wang",

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AU - Xie, Yinlong

AU - Liu, Binghang

AU - Yang, Hailong

AU - Zheng, Hancheng

AU - Li, Jian

AU - Li, Bo

AU - Wang, Yu

AU - Yang, Fang

AU - Sun, Peng

AU - Liu, Siyang

AU - Gao, Peng

AU - Huang, Haodong

AU - Sun, Jing

AU - Chen, Dan

AU - He, Guangzhu

AU - Huang, Weihua

AU - Huang, Zheng

AU - Li, Yue

AU - Tellier, Laurent C.A.M.

AU - Liu, Xiao

AU - Feng, Qiang

AU - Xu, Xun

AU - Zhang, Xiuqing

AU - Bolund, Lars

AU - Krogh, Anders

AU - Kristiansen, Karsten

AU - Drmanac, Radoje

AU - Drmanac, Snezana

AU - Nielsen, Rasmus

AU - Li, Songgang

AU - Wang, Jian

AU - Yang, Huanming

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AU - Wong, Gane Ka-Shu

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De novo assembly of a haplotype-resolved human genome

Abstract

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