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Quantitative detection of low-abundance somatic structural variants in normal cells by high-throughput sequencing

Nature Methods volume 13, pages 584586 (2016) | Download Citation

Abstract

The detection and quantification of low-abundance somatic DNA mutations by high-throughput sequencing is challenging because of the difficulty of distinguishing errors from true mutations. There are several approaches available for analyzing somatic point mutations and small insertions or deletions, but an accurate genome-wide assessment of somatic structural variants (somSVs) in bulk DNA is still not possible. Here we present Structural Variant Search (SVS), a method to accurately detect rare somSVs by low-coverage sequencing. We demonstrate direct quantitative assessment of elevated somSV frequencies induced by known clastogenic compounds in human primary cells.

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Acknowledgements

This research was supported by the NIH (grants AG017242, AG047200, and AG038072 to J.V.), the Glenn Foundation for Medical Research (J.V.), the Albert Einstein College of Medicine Human Genome Program (pilot grant to A.Y.M.) the Einstein-Nathan Shock Center of Excellence pilot and feasibility grant to A.Y.M., and the Ministry of Education and Science of the Russian Federation (grant 6.149.2014/K to V.N.P.).

Author information

Affiliations

  1. Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, USA.

    • Wilber Quispe-Tintaya
    • , Tatyana Gorbacheva
    • , Moonsook Lee
    • , Jan Vijg
    •  & Alexander Y Maslov
  2. Department of Genetics, Cytology, and Bioengineering, Voronezh State University, Voronezh, Russia.

    • Tatyana Gorbacheva
    •  & Vasily N Popov
  3. Department of Applied and System Software, Voronezh State University, Voronezh, Russia.

    • Sergei Makhortov

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Contributions

A.Y.M. and J.V. conceived the idea and wrote the manuscript; W.Q.-T., T.G., and M.L. performed the experiments; A.Y.M., J.V., and V.N.P. analyzed data; A.Y.M. wrote SVS; and S.M. advised on software design.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Jan Vijg or Alexander Y Maslov.

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Supplementary information

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    Supplementary Text and Figures

    Supplementary Figures 1–9, Supplementary Tables 1–5

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    Supplementary Software

    Archived SVS variant caller

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DOI

https://doi.org/10.1038/nmeth.3893

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