Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

CREST maps somatic structural variation in cancer genomes with base-pair resolution

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.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Mapping SV breakpoints using soft-clipped reads.
Figure 2: SV validation result for one T-ALL sample (SJTALL003).

References

  1. Feuk, L., Carson, A.R. & Scherer, S.W. Nat. Rev. Genet. 7, 85–97 (2006).

    Article  CAS  Google Scholar 

  2. Maher, C.A. et al. Nature 458, 97–101 (2009).

    Article  CAS  Google Scholar 

  3. Campbell, P.J. et al. Nat. Genet. 40, 722–729 (2008).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  6. Hormozdiari, F., Alkan, C., Eichler, E.E. & Sahinalp, S.C. Genome Res. 19, 1270–1278 (2009).

    Article  CAS  Google Scholar 

  7. Sindi, S., Helman, E., Bashir, A. & Raphael, B.J. Bioinformatics 25, i222–i230 (2009).

    Article  CAS  Google Scholar 

  8. Korbel, J.O. et al. Science 318, 420–426 (2007).

    Article  CAS  Google Scholar 

  9. Kidd, J.M. et al. Nature 453, 56–64 (2008).

    Article  CAS  Google Scholar 

  10. Li, H. & Durbin, R. Bioinformatics 25, 1754–1760 (2009).

    Article  CAS  Google Scholar 

  11. Ye, K., Schulz, M.H., Long, Q., Apweiler, R. & Ning, Z. Bioinformatics 25, 2865–2871 (2009).

    Article  CAS  Google Scholar 

  12. Pleasance, E.D. et al. Nature 463, 191–196 (2010).

    Article  CAS  Google Scholar 

  13. Mills, R.E. et al. Nature 470, 59–65 (2011).

    Article  CAS  Google Scholar 

  14. Abel, H.J. et al. Bioinformatics 26, 2684–2688 (2010).

    Article  CAS  Google Scholar 

  15. Handsaker, R.E., Korn, J.M., Nemesh, J. & McCarroll, S.A. Nat. Genet. 43, 269–276 (2011).

    Article  CAS  Google Scholar 

  16. Huang, X. & Madan, A. Genome Res. 9, 868–877 (1999).

    Article  CAS  Google Scholar 

  17. Kent, W.J. Genome Res. 12, 656–664 (2002).

    Article  CAS  Google Scholar 

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

  19. Parsons, D.W. et al. Science 331, 435–439 (2011).

    Article  CAS  Google Scholar 

  20. Li, H., Ruan, J. & Durbin, R. Genome Res. 18, 1851–1858 (2008).

    Article  CAS  Google Scholar 

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

Authors and Affiliations

Authors

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.

Corresponding author

Correspondence to Jinghui Zhang.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–10, Supplementary Tables 1, 3–4, Supplementary Data 1–3, Supplementary Discussion (PDF 1436 kb)

Supplementary Table 2

Summary of CREST SV analysis results for COLO-829. (XLS 37 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Wang, J., Mullighan, C., Easton, J. et al. CREST maps somatic structural variation in cancer genomes with base-pair resolution. Nat Methods 8, 652–654 (2011). https://doi.org/10.1038/nmeth.1628

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

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

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing