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Detection of structural variants and indels within exome data

Abstract

We report an algorithm to detect structural variation and indels from 1 base pair (bp) to 1 Mbp within exome sequence data sets. Splitread uses one end–anchored placements to cluster the mappings of subsequences of unanchored ends to identify the size, content and location of variants with high specificity and sensitivity. The algorithm discovers indels, structural variants, de novo events and copy number–polymorphic processed pseudogenes missed by other methods.

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Figure 1: Splitread definition and analyses.
Figure 2: Validation of processed pseudogenes.

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Sequence Read Archive

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Acknowledgements

We thank T. Brown and S. Girirajan for helpful comments during manuscript preparation. This work was supported by Simons Foundation Autism Research Initiative award SFARI191889 (E.E.E.) and US National Institutes of Health grants HD065285 (E.E.E.), HHSN273200800010C (D.A.N.) and HL 102926 (D.A.N.). E.E.E. is funded by the Howard Hughes Medical Institute.

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Authors

Contributions

E.K. designed and implemented the Splitread algorithm; E.K. and C.A. analyzed data; B.J.O., L.V., M.J.R. and D.A.N. generated sequencing data; M.Y.D. and K.M. carried out validation experiments and analyzed processed pseudogenes and E.K., C.A. and E.E.E. wrote the manuscript.

Corresponding author

Correspondence to Evan E Eichler.

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Competing interests

E.E.E. is a member of the Scientific Advisory Board of Pacific Biosciences.

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Supplementary Figures 1 and 2, Supplementary Tables 1–6 and Supplementary Note (PDF 2526 kb)

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Karakoc, E., Alkan, C., O'Roak, B. et al. Detection of structural variants and indels within exome data. Nat Methods 9, 176–178 (2012). https://doi.org/10.1038/nmeth.1810

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