title: De novo assembly of a haplotype-resolved human genome.
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.
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] BGI-Tianjin, Tianjin, China. [3] Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Cao
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] BGI-Tianjin, Tianjin, China.
authors.forename: Honglong
authors.initials: H
authors.lastname: Wu
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] HKU-BGI Bioinformatics Algorithms and Core Technology Research Laboratory, Hong Kong, China.
authors.forename: Ruibang
authors.initials: R
authors.lastname: Luo
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, China.
authors.forename: Shujia
authors.initials: S
authors.lastname: Huang
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, China.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Sun
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Tong
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] HKU-BGI Bioinformatics Algorithms and Core Technology Research Laboratory, Hong Kong, China. [3] School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, China.
authors.forename: Yinlong
authors.initials: Y
authors.lastname: Xie
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] HKU-BGI Bioinformatics Algorithms and Core Technology Research Laboratory, Hong Kong, China.
authors.forename: Binghang
authors.initials: B
authors.lastname: Liu
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Yang
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Hancheng
authors.initials: H
authors.lastname: Zheng
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Siyang
authors.initials: S
authors.lastname: Liu
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, China.
authors.forename: Haodong
authors.initials: H
authors.lastname: Huang
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Guangzhu
authors.initials: G
authors.lastname: He
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Huang
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Huang
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Laurent C A M
authors.initials: LC
authors.lastname: Tellier
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Feng
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Xu
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] Institute of Biomedicine, University of Aarhus, Aarhus, Denmark. [3] Danish Center for Translational Breast Cancer Research, Copenhagen, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Bolund
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anders
authors.identifier: 0000000251476282
authors.initials: A
authors.lastname: Krogh
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
authors.affiliation: Complete Genomics Inc., Mountain View, California, USA.
authors.forename: Radoje
authors.initials: R
authors.lastname: Drmanac
authors.affiliation: Complete Genomics Inc., Mountain View, California, USA.
authors.forename: Snezana
authors.initials: S
authors.lastname: Drmanac
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] Department of Integrative Biology, University of California, Berkeley, California, USA. [3] Department of Statistics, University of California, Berkeley, California, USA.
authors.forename: Rasmus
authors.initials: R
authors.lastname: Nielsen
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Songgang
authors.initials: S
authors.lastname: Li
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] James D. Watson Institute of Genome Sciences, Hangzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] James D. Watson Institute of Genome Sciences, Hangzhou, China. [3] Princess Al Jawhara Albrahim Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Huanming
authors.initials: H
authors.lastname: Yang
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Yingrui
authors.initials: Y
authors.lastname: Li
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada. [3] Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Gane Ka-Shu
authors.initials: GK
authors.lastname: Wong
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] Department of Biology, University of Copenhagen, Copenhagen, Denmark. [3] Princess Al Jawhara Albrahim Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia. [4] Macau University of Science and Technology, Taipa, Macau, China. [5] Department of Medicine and State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
mesh_terms: D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002874:Chromosome Mapping; D004171:Diploidy; D015894:Genome, Human; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine; D017422:Sequence Analysis, DNA