Abstract

We developed 'clipping reveals structure' (CREST), an algorithm that uses next-generation sequencing reads with partial alignments to a reference genome to directly map structural variations at the nucleotide level of resolution. Application of CREST to whole-genome sequencing data from five pediatric T-lineage acute lymphoblastic leukemias (T-ALLs) and a human melanoma cell line, COLO-829, identified 160 somatic structural variations. Experimental validation exceeded 80%, demonstrating that CREST had a high predictive accuracy.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    , & Nat. Rev. Genet. 7, 85–97 (2006).

  2. 2.

    et al. Nature 458, 97–101 (2009).

  3. 3.

    et al. Nat. Genet. 40, 722–729 (2008).

  4. 4.

    et al. Nature 464, 999–1005 (2010).

  5. 5.

    et al. Nat. Methods 6, 677–681 (2009).

  6. 6.

    , , & Genome Res. 19, 1270–1278 (2009).

  7. 7.

    , , & Bioinformatics 25, i222–i230 (2009).

  8. 8.

    et al. Science 318, 420–426 (2007).

  9. 9.

    et al. Nature 453, 56–64 (2008).

  10. 10.

    & Bioinformatics 25, 1754–1760 (2009).

  11. 11.

    , , , & Bioinformatics 25, 2865–2871 (2009).

  12. 12.

    et al. Nature 463, 191–196 (2010).

  13. 13.

    et al. Nature 470, 59–65 (2011).

  14. 14.

    et al. Bioinformatics 26, 2684–2688 (2010).

  15. 15.

    , , & Nat. Genet. 43, 269–276 (2011).

  16. 16.

    & Genome Res. 9, 868–877 (1999).

  17. 17.

    Genome Res. 12, 656–664 (2002).

  18. 18.

    Cancer Genome Atlas Research Network. Nature 455, 1061–1068 (2008).

  19. 19.

    et al. Science 331, 435–439 (2011).

  20. 20.

    , & Genome Res. 18, 1851–1858 (2008).

Download references

Acknowledgements

This study was supported by St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project, Cancer Center support grant P30 CA021765 from the US National Cancer Institute and the American Lebanese Syrian Associated Charities of St. Jude Children's Research Hospital. We thank K. Ye for stimulating discussion on the analysis of the COLO-829 cell line. C.G.M. is supported as a Pew Scholar in the Biomedical Sciences. S.L.H. was supported by a Haematology Society of Australasia Travelling Fellowship.

Author information

Affiliations

  1. Department of Information Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

    • Jianmin Wang
    • , Jing Ma
    • , David Zhao
    • , John C Obenauer
    •  & Clayton Naeve
  2. Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

    • Charles G Mullighan
    • , Sue L Heatley
    • , Linda Holmfeldt
    • , Debbie Payne-Turner
    • , Lei Wei
    •  & James R Downing
  3. Pediatric Cancer Genome Project, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

    • John Easton
    •  & Stefan Roberts
  4. Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

    • Stefan Roberts
    • , Michael C Rusch
    • , Lei Wei
    •  & Jinghui Zhang
  5. Department of Medical Engineering, Washington University, St. Louis, Missouri, USA.

    • Stefan Roberts
  6. The Genome Center at Washington University, St. Louis, Missouri, USA.

    • Ken Chen
    • , Christopher C Harris
    • , Li Ding
    • , Xian Fan
    • , Elaine R Mardis
    •  & Richard K Wilson
  7. Department of Genetics, Washington University, St. Louis, Missouri, USA.

    • Ken Chen
    • , Li Ding
    • , Elaine R Mardis
    •  & Richard K Wilson

Authors

  1. Search for Jianmin Wang in:

  2. Search for Charles G Mullighan in:

  3. Search for John Easton in:

  4. Search for Stefan Roberts in:

  5. Search for Sue L Heatley in:

  6. Search for Jing Ma in:

  7. Search for Michael C Rusch in:

  8. Search for Ken Chen in:

  9. Search for Christopher C Harris in:

  10. Search for Li Ding in:

  11. Search for Linda Holmfeldt in:

  12. Search for Debbie Payne-Turner in:

  13. Search for Xian Fan in:

  14. Search for Lei Wei in:

  15. Search for David Zhao in:

  16. Search for John C Obenauer in:

  17. Search for Clayton Naeve in:

  18. Search for Elaine R Mardis in:

  19. Search for Richard K Wilson in:

  20. Search for James R Downing in:

  21. Search for Jinghui Zhang in:

Contributions

J.Z. conceived and designed the CREST algorithm. J.W. implemented the algorithm. J.R.D. and C.G.M. designed the experiment. J.W., J.Z., S.R., J.M., M.C.R., K.C., C.C.H., L.D., X.F. and L.W. analyzed the data. C.G.M., J.E., S.L.H., L.H. and D.P.-T. performed validation assay. E.R.M. and R.K.W. supervised whole-genome sequencing data generation. D.Z., J.C.O. and C.N. set up the computing infrastructure. J.R.D. and J.Z. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Jinghui Zhang.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–10, Supplementary Tables 1, 3–4, Supplementary Data 1–3, Supplementary Discussion

Excel files

  1. 1.

    Supplementary Table 2

    Summary of CREST SV analysis results for COLO-829.

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/nmeth.1628

Further reading