De novo assembly of a haplotype-resolved human genome

Research output: Contribution to journalJournal articleResearchpeer-review

  • 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
  • Radoje Drmanac
  • Snezana Drmanac
  • Rasmus Nielsen
  • Songgang Li
  • Jian Wang
  • Huanming Yang
  • Yingrui Li
  • Gane Ka-Shu Wong
  • Jun Wang

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 languageEnglish
JournalNature Biotechnology
Issue number6
Pages (from-to)617-626
Number of pages10
Publication statusPublished - 2015

ID: 138373867