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Cited by 1,470Genomics and Phylogenetic StudiesGenomics and Chromatin DynamicsGenomic variations and chromosomal abnormalities

Chromosome-scale scaffolding of de novo genome assemblies based on chromatin interactions

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Burton, Joshua N, Adey, Andrew, Patwardhan, Rupali P, Qiu, Ruolan, Kitzman, Jacob O, Shendure, Jay·2013·Nature Biotechnology
DOI 10.1038/nbt.2727PMC PMC4117202
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Abstract

Genomes assembled de novo from short reads are highly fragmented relative to the finished chromosomes of Homo sapiens and key model organisms generated by the Human Genome Project. To address this problem, we need scalable, cost-effective methods to obtain assemblies with chromosome-scale contiguity. Here we show that genome-wide chromatin interaction data sets, such as those generated by Hi-C, are a rich source of long-range information for assigning, ordering and orienting genomic sequences to chromosomes, including across centromeres. To exploit this finding, we developed an algorithm that uses Hi-C data for ultra-long-range scaffolding of de novo genome assemblies. We demonstrate the approach by combining shotgun fragment and short jump mate-pair sequences with Hi-C data to generate chromosome-scale de novo assemblies of the human, mouse and Drosophila genomes, achieving--for the human genome--98% accuracy in assigning scaffolds to chromosome groups and 99% accuracy in ordering and orienting scaffolds within chromosome groups. Hi-C data can also be used to validate chromosomal translocations in cancer genomes.

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  • High-throughput, inexpensive proximity sequencing methods emerged as powerful tools to scaffold subchromosomal genomic contigs into chromosome-scale sequences.

    “High-throughput, inexpensive proximity sequencing methods (reviewed in 83) emerged as powerful tools to scaffold subchromosomal genomic contigs into sequences reconstructing whole chromosomes (i.e., chromosome-scale) (54, 55)”

    From Topological Approaches in Animal Comparative Genomics (2026) · cites this paper as [54]

  • Genome sequencing and assembly have become increasingly affordable and computationally tractable thanks to long-read sequencing technologies, DNA proximity ligation sequencing techniques, and genome sequencing consortia.

    “Genome sequencing and assembly have become increasingly affordable and computationally tractable thanks to the development of long-read sequencing technologies like the Pacific Biosciences and Oxford Nanopore platforms (52); the development of DNA proximity ligation sequencing techniques, like Hi-C, for genome scaffolding (53–55); and the efforts of genome sequencing consortia (1, 2, 4, 56)”

    From Topological Approaches in Animal Comparative Genomics (2026) · cites this paper as [54]

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Research works printed but not linked: 26

  1. [2]International Human Genome Sequencing Consortium Finishing the euchromatic sequence of the human genome Nature 431 931 945 2004 15496913
  2. [3]Shendure J Ji H Next-generation DNA sequencing Nature Biotechnology 26 1 11 2008 18846087
  3. [4]Shendure J Lieberman-Aiden E The expanding scope of DNA sequencing Nature Biotechnology 30 1084 94 2012 PMC4149750 23138308
  4. [6]Gnerre S High-quality draft assemblies of mammalian genomes from massively parallel sequence data Proceedings of the National Academy of Sciences of the United States of America 108 1 6 2011
  5. [9]Kitzman JO Haplotype-resolved genome sequencing of a Gujarati Indian individual Nature Biotechnology 29 1 6 2011 PMC3116788 21170042
  6. [10]Zhang G The oyster genome reveals stress adaptation and complexity of shell formation Nature 490 49 54 2012 22992520
  7. [11]Schwartz DC Ordered restriction maps of Saccharomyces cerevisiae chromosomes constructed by optical mapping Science 262 110 4 1993 8211116
  8. [12]Zhang Q The genome of Prunus mume Nature Communications 3 1318 2012 PMC3535359 23271652
  9. [13]Dong Y Sequencing and automated whole-genome optical mapping of the genome of a domestic goat (Capra hircus) Nature Biotechnology 31 135 41 2013 23263233
  10. [14]Lam E Genome mapping on nanochannel arrays for structural variation analysis and sequence assembly Nature Biotechnology 30 771 6 2012 PMC3817024 22797562
  11. [15]Baird NA Rapid SNP discovery and genetic mapping using sequenced RAD markers PLoS One 3 e3376 2008 18852878 PMC2557064
  12. [16]Genome 10K Community of Scientists Genome 10K: a proposal to obtain whole-genome sequence for 10,000 vertebrate species The Journal of Heredity 100 659 74 2009 19892720 PMC2877544
  13. [17]Lieberman-Aiden E Comprehensive mapping of long-range interactions reveals folding principles of the human genome Science 326 289 293 2009 19815776 PMC2858594
  14. [18]Duan Z A three-dimensional model of the yeast genome Nature 465 363 7 2010 20436457 PMC2874121
  15. [19]Eisen M Spellman P Brown P Botstein D Cluster analysis and display of genome-wide expression patterns Proceedings of the National Academy of Sciences of the United States of America 95 14863 8 1998 9843981 PMC24541
  16. [21]Yaffe E Tanay A Probabilistic modeling of Hi-C contact maps eliminates systematic biases to characterize global chromosomal architecture Nature Genetics 43 1059 65 2011 22001755
  17. [22]Mackay T The Drosophila melanogaster Genetic Reference Panel Nature 482 173 8 2012 22318601 PMC3683990
  18. [23]Sexton T Three-dimensional folding and functional organization principles of the Drosophila genome Cell 148 458 72 2012 22265598
  19. [24]Landry J The genomic and transcriptomic landscape of a HeLa cell line Genes | Genomes | Genetics 1 27 2013 23550136 PMC3737162
  20. [25]Adey A The haplotype-resolved genome and epigenome of the aneuploid HeLa cancer cell line Nature 500 207 211 2013 23925245 PMC3740412
  21. [26]Simonis M High-resolution identification of balanced and complex chromosomal rearrangements by 4C technology Nature Methods 6 837 42 2009 19820713
  22. [27]Macville M Comprehensive and definitive molecular cytogenetic characterization of HeLa cells by spectral karyotyping Cancer Research 59 1 11 1999 9892199
  23. [28]Moissiard G MORC family ATPases required for heterochromatin condensation and gene silencing Science 336 1448 51 2012 22555433 PMC3376212
  24. [29]Fraley C Raftery AE How Many Clusters? Which Clustering Method? Answers Via Model-Based Cluster Analysis The Computer Journal 41 578 588 1998
  25. [30]Jung Y Park H Du DZ Drake B A decision criterion for the optimal number of clusters in hierarchical clustering Journal of Global Optimization 1 21 2003
  26. [33]van Berkum NL Hi-C: a method to study the three-dimensional architecture of genomes Journal of Visualized Experiments 1 7 2010 20461051 PMC3149993

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Authors
Burton, J. N., Adey, A., Patwardhan, R. P., Qiu, R., Kitzman, J. O., & Shendure, J.
Affiliations
University of Washington (US)
Corresponding author
  • Burton, Joshua N
  • Shendure, Jay
ORCID
Venue
Nature Biotechnology
Publisher
Springer Science and Business Media LLC
Published
2013-12
Volume
31
Issue
12
Pages
1119-1125
ISSN
  • 0733-222X (ISSN-L)
  • 1087-0156
  • 1546-1696
DOI
10.1038/nbt.2727
PMC
PMC4117202
OpenAlex
W2118970626
Cited by
1,470
References
6
Citations by year
2026: 102 · 2025: 132 · 2024: 197 · 2023: 162 · 2022: 207 · 2021: 208 · 2020: 146 · 2019: 104 · 2018: 81 · 2017: 52 · 2016: 24 · 2015: 23 · 2014: 24 · 2013: 2
FWCI
9.17
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Biotechnology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Science Foundation
  • National Human Genome Research Institute (HG006283, R01HG006283, T32HG000035)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
Keywords
de novo genome assembly, Hi-C, chromatin interactions, centromere, human genome, mouse genome, Drosophila genome, chromosomal translocation, cancer genome, mate-pair sequencing
MeSH terms
Algorithms, Animals, Base Sequence, Chromatin, Chromosome Mapping, Drosophila, Humans, Molecular Sequence Data, Sequence Analysis, DNA, Contig Mapping, Mice

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