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