RT Journal Article
SR Electronic
T1 Multi-platform discovery of haplotype-resolved structural variation in human genomes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 193144
DO 10.1101/193144
A1 Mark J.P. Chaisson
A1 Ashley D. Sanders
A1 Xuefang Zhao
A1 Ankit Malhotra
A1 David Porubsky
A1 Tobias Rausch
A1 Eugene J. Gardner
A1 Oscar Rodriguez
A1 Li Guo
A1 Ryan L. Collins
A1 Xian Fan
A1 Jia Wen
A1 Robert E. Handsaker
A1 Susan Fairley
A1 Zev N. Kronenberg
A1 Xiangmeng Kong
A1 Fereydoun Hormozdiari
A1 Dillon Lee
A1 Aaron M. Wenger
A1 Alex Hastie
A1 Danny Antaki
A1 Peter Audano
A1 Harrison Brand
A1 Stuart Cantsilieris
A1 Han Cao
A1 Eliza Cerveira
A1 Chong Chen
A1 Xintong Chen
A1 Chen-Shan Chin
A1 Zechen Chong
A1 Nelson T. Chuang
A1 Christine C. Lambert
A1 Deanna M. Church
A1 Laura Clarke
A1 Andrew Farrell
A1 Joey Flores
A1 Timur Galeev
A1 David Gorkin
A1 Madhusudan Gujral
A1 Victor Guryev
A1 William Haynes Heaton
A1 Jonas Korlach
A1 Sushant Kumar
A1 Jee Young Kwon
A1 Jong Eun Lee
A1 Joyce Lee
A1 Wan-Ping Lee
A1 Sau Peng Lee
A1 Shantao Li
A1 Patrick Marks
A1 Karine Viaud-Martinez
A1 Sascha Meiers
A1 Katherine M. Munson
A1 Fabio Navarro
A1 Bradley J. Nelson
A1 Conor Nodzak
A1 Amina Noor
A1 Sofia Kyriazopoulou-Panagiotopoulou
A1 Andy Pang
A1 Yunjiang Qiu
A1 Gabriel Rosanio
A1 Mallory Ryan
A1 Adrian Stütz
A1 Diana C.J. Spierings
A1 Alistair Ward
A1 AnneMarie E. Welch
A1 Ming Xiao
A1 Wei Xu
A1 Chengsheng Zhang
A1 Qihui Zhu
A1 Xiangqun Zheng-Bradley
A1 Ernesto Lowy
A1 Sergei Yakneen
A1 Steven McCarroll
A1 Goo Jun
A1 Li Ding
A1 Chong Lek Koh
A1 Bing Ren
A1 Paul Flicek
A1 Ken Chen
A1 Mark B. Gerstein
A1 Pui-Yan Kwok
A1 Peter M. Lansdorp
A1 Gabor Marth
A1 Jonathan Sebat
A1 Xinghua Shi
A1 Ali Bashir
A1 Kai Ye
A1 Scott E. Devine
A1 Michael Talkowski
A1 Ryan E. Mills
A1 Tobias Marschall
A1 Jan O. Korbel
A1 Evan E. Eichler
A1 Charles Lee
YR 2018
UL http://biorxiv.org/content/early/2018/06/13/193144.abstract
AB The incomplete identification of structural variants (SVs) from whole-genome sequencing data limits studies of human genetic diversity and disease association. Here, we apply a suite of long-read, short-read, and strand-specific sequencing technologies, optical mapping, and variant discovery algorithms to comprehensively analyze three human parent–child trios to define the full spectrum of human genetic variation in a haplotype-resolved manner. We identify 818,054 indel variants (<50 bp) and 27,622 SVs (≥50 bp) per human genome. We also discover 156 inversions per genome—most of which previously escaped detection. Fifty-eight of the inversions we discovered intersect with the critical regions of recurrent microdeletion and microduplication syndromes. Taken together, our SV callsets represent a sevenfold increase in SV detection compared to most standard high-throughput sequencing studies, including those from the 1000 Genomes Project. The method and the dataset serve as a gold standard for the scientific community and we make specific recommendations for maximizing structural variation sensitivity for future large-scale genome sequencing studies.