title: Long-read sequencing and de novo assembly of a Chinese genome.
abstract: Short-read sequencing has enabled the de novo assembly of several individual human genomes, but with inherent limitations in characterizing repeat elements. Here we sequence a Chinese individual HX1 by single-molecule real-time (SMRT) long-read sequencing, construct a physical map by NanoChannel arrays and generate a de novo assembly of 2.93 Gb (contig N50: 8.3 Mb, scaffold N50: 22.0 Mb, including 39.3 Mb N-bases), together with 206 Mb of alternative haplotypes. The assembly fully or partially fills 274 (28.4%) N-gaps in the reference genome GRCh38. Comparison to GRCh38 reveals 12.8 Mb of HX1-specific sequences, including 4.1 Mb that are not present in previously reported Asian genomes. Furthermore, long-read sequencing of the transcriptome reveals novel spliced genes that are not annotated in GENCODE and are missed by short-read RNA-Seq. Our results imply that improved characterization of genome functional variation may require the use of a range of genomic technologies on diverse human populations.
authors.affiliation: Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou 510632, China.|Ministry of Education Joint International Research Laboratory of CNS Regeneration, Jinan University, Guangzhou 510632, China.|Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Shi
authors.affiliation: Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Chengliang
authors.initials: C
authors.lastname: Dong
authors.affiliation: Department of Genome Sciences, Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA.
authors.forename: John
authors.initials: J
authors.lastname: Huddleston
authors.affiliation: Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Hui
authors.identifier: 0000-0001-7325-9425
authors.initials: H
authors.lastname: Yang
authors.affiliation: Genetic, Molecular, and Cellular Biology Program, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Han
authors.affiliation: Wuhan Institute of Biotechnology, Wuhan 430000, China.
authors.forename: Aisi
authors.initials: A
authors.lastname: Fu
authors.affiliation: Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Quan
authors.initials: Q
authors.lastname: Li
authors.affiliation: Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou 510632, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou 510632, China.
authors.forename: Siyi
authors.initials: S
authors.lastname: Gong
authors.affiliation: Department of Pediatrics, The Ohio State University, and The Research Institute at Nationwide Children's Hospital, Columbus, Ohio 43205, USA.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Lintner
authors.affiliation: Wuhan Institute of Biotechnology, Wuhan 430000, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Ding
authors.affiliation: Wuhan Institute of Biotechnology, Wuhan 430000, China.
authors.forename: Zou
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Nextomics Biosciences, Wuhan 430000, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Hu
authors.affiliation: Nextomics Biosciences, Wuhan 430000, China.
authors.forename: Depeng
authors.initials: D
authors.lastname: Wang
authors.affiliation: School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430000, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, New York, New York 11797, USA.
authors.forename: Gholson J
authors.initials: GJ
authors.lastname: Lyon
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Yongtao
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Departments of Systems Biology and Biomedical Informatics, Columbia University, New York, New York 10032, USA.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California 90089, USA.|Department of Psychiatry &Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
authors.forename: Oleg V
authors.initials: OV
authors.lastname: Evgrafov
authors.affiliation: Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California 90089, USA.|Department of Psychiatry &Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
authors.forename: James A
authors.identifier: 0000-0002-3307-5741
authors.initials: JA
authors.lastname: Knowles
authors.affiliation: National Center for Biotechnology Information, U.S. National Library of Medicine, Bethesda, Maryland 20894, USA.
authors.forename: Francoise
authors.initials: F
authors.lastname: Thibaud-Nissen
authors.affiliation: National Center for Biotechnology Information, U.S. National Library of Medicine, Bethesda, Maryland 20894, USA.
authors.forename: Valerie
authors.initials: V
authors.lastname: Schneider
authors.affiliation: Department of Pediatrics, The Ohio State University, and The Research Institute at Nationwide Children's Hospital, Columbus, Ohio 43205, USA.
authors.forename: Chack-Yung
authors.initials: CY
authors.lastname: Yu
authors.affiliation: Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou 510632, China.|Ministry of Education Joint International Research Laboratory of CNS Regeneration, Jinan University, Guangzhou 510632, China.|Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
authors.forename: Libing
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Genome Sciences, Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Evan E
authors.initials: EE
authors.lastname: Eichler
authors.affiliation: Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou 510632, China.|Ministry of Education Joint International Research Laboratory of CNS Regeneration, Jinan University, Guangzhou 510632, China.|Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.|Department of Ophthalmology, The University of Hong Kong, Hong Kong, China.|State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China.
authors.forename: Kwok-Fai
authors.initials: KF
authors.lastname: So
authors.affiliation: Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California 90089, USA.|Department of Psychiatry &Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
mesh_terms: D044466:Asian People / Q000235:genetics*; D015894:Genome, Human; D056914:Genomic Structural Variation; D006801:Humans; D008297:Male; D017422:Sequence Analysis, DNA; D017423:Sequence Analysis, RNA; D059467:Transcriptome