title: Assembly and diploid architecture of an individual human genome via single-molecule technologies.
abstract: We present the first comprehensive analysis of a diploid human genome that combines single-molecule sequencing with single-molecule genome maps. Our hybrid assembly markedly improves upon the contiguity observed from traditional shotgun sequencing approaches, with scaffold N50 values approaching 30 Mb, and we identified complex structural variants (SVs) missed by other high-throughput approaches. Furthermore, by combining Illumina short-read data with long reads, we phased both single-nucleotide variants and SVs, generating haplotypes with over 99% consistency with previous trio-based studies. Our work shows that it is now possible to integrate single-molecule and high-throughput sequence data to generate de novo assembled genomes that approach reference quality.
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Pendleton
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Sebra
authors.affiliation: BioNano Genomics, San Diego, California, USA.
authors.forename: Andy Wing Chun
authors.initials: AW
authors.lastname: Pang
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Ajay
authors.initials: A
authors.lastname: Ummat
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Oscar
authors.initials: O
authors.lastname: Franzen
authors.affiliation: Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Tobias
authors.identifier: 0000000157735620
authors.initials: T
authors.lastname: Rausch
authors.affiliation: Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Stütz
authors.affiliation: BioNano Genomics, San Diego, California, USA.
authors.forename: William
authors.initials: W
authors.lastname: Stedman
authors.affiliation: BioNano Genomics, San Diego, California, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Anantharaman
authors.affiliation: BioNano Genomics, San Diego, California, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Hastie
authors.affiliation: BioNano Genomics, San Diego, California, USA.
authors.forename: Heng
authors.initials: H
authors.lastname: Dai
authors.affiliation: Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Markus Hsi-Yang
authors.initials: MH
authors.lastname: Fritz
authors.affiliation: BioNano Genomics, San Diego, California, USA.
authors.forename: Han
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Ariella
authors.initials: A
authors.lastname: Cohain
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Gintaras
authors.initials: G
authors.lastname: Deikus
authors.affiliation: The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Russell E
authors.initials: RE
authors.lastname: Durrett
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Blanchard
authors.affiliation: The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Roger
authors.initials: R
authors.lastname: Altman
authors.affiliation: Pacific Biosciences, Menlo Park, California, USA.
authors.forename: Chen-Shan
authors.identifier: 0000000343942455
authors.initials: CS
authors.lastname: Chin
authors.affiliation: Pacific Biosciences, Menlo Park, California, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Pacific Biosciences, Menlo Park, California, USA.
authors.forename: Ellen E
authors.initials: EE
authors.lastname: Paxinos
authors.affiliation: 1] Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany. [2] European Bioinformatics Institute, European Molecular Biology Laboratory, Hinxton, UK.
authors.forename: Jan O
authors.identifier: 0000000227983794
authors.initials: JO
authors.lastname: Korbel
authors.affiliation: 1] Laboratory of Neuro-Oncology, The Rockefeller University, New York, New York, USA. [2] Howard Hughes Medical Institute, New York, New York, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Darnell
authors.affiliation: 1] The Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA. [2] The Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.
authors.forename: W Richard
authors.initials: WR
authors.lastname: McCombie
authors.affiliation: Institute for Human Genetics, University of California-San Francisco, San Francisco, California, USA.
authors.forename: Pui-Yan
authors.initials: PY
authors.lastname: Kwok
authors.affiliation: 1] The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medical College, New York, New York, USA. [2] Department of Medicine, Division of Hematology/Oncology, Weill Cornell Medical College, New York, New York, USA. [3] The Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Mason
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Eric E
authors.initials: EE
authors.lastname: Schadt
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Bashir
mesh_terms: D000465:Algorithms; D002874:Chromosome Mapping; D019295:Computational Biology / Q000379:methods*; D004171:Diploidy; D015723:Gene Library; D014644:Genetic Variation; D016678:Genome; D015894:Genome, Human; D006239:Haplotypes; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D009711:Nucleotides / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA; D020080:Tandem Repeat Sequences
chemical_list: D009711:Nucleotides