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High-throughput genome scaffolding from in vivo DNA interaction frequency

Nature Biotechnology volume 31, pages 1143–1147 (2013)Cite this article

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Abstract

Despite advances in DNA sequencing technology, assembly of complex genomes remains a major challenge, particularly for genomes sequenced using short reads, which yield highly fragmented assemblies1,2,3. Here we show that genome-wide in vivo chromatin interaction frequency data, which are measurable with chromosome conformation capture–based experiments, can be used as genomic distance proxies to accurately position individual contigs without requiring any sequence overlap. We also use these data to construct approximate genome scaffolds de novo. Applying our approach to incomplete regions of the human genome, we predict the positions of 65 previously unplaced contigs, in agreement with alternative methods in 26/31 cases attempted in common. Our approach can theoretically bridge any gap size and should be applicable to any species for which global chromatin interaction data can be generated.

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Figure 1: Interaction frequency accurately predicts chromosome and locus for scaffold augmentation.
Figure 2: Scaffold augmentation of the human genome.
Figure 3: De novo karyotyping (chromosome assignment).
Figure 4: Accurate de novo chromosome scaffolding with interaction frequencies.

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Change history

  • 04 December 2013

    In the version of this supplementary file originally posted online, a section entitled Supplementary Methods was inadvertently included in the file and the legends for tables and figures omitted. The errors have been corrected in this file as of 4 December 2013.

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Acknowledgements

We thank B.R. Lajoie for help with processing of the Hi-C data. We thank the members of the Dekker Lab and G. Fudenberg for helpful discussions. This study is supported by the National Human Genome Research Institute (HG003143 to J.D.). N.K. is supported by a Long-Term Fellowship from the Human Frontier Science Program.

Author information

Authors and Affiliations

  1. Department of Biochemistry and Molecular Pharmacology, Program in Systems Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA

    Noam Kaplan & Job Dekker

Authors
  1. Noam Kaplan
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Contributions

N.K. and J.D. conceived the strategy for genome assembly. N.K. performed all analyses and developed all computational approaches. N.K. and J.D. wrote the paper.

Corresponding authors

Correspondence to Noam Kaplan or Job Dekker.

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The authors declare no competing financial interests.

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Supplementary Discussion, Supplementary Figure 1 and Supplementary Tables 1–3 (PDF 1383 kb)

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Kaplan, N., Dekker, J. High-throughput genome scaffolding from in vivo DNA interaction frequency. Nat Biotechnol 31, 1143–1147 (2013). https://doi.org/10.1038/nbt.2768

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