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MoDIL: detecting small indels from clone-end sequencing with mixtures of distributions

Nature Methods volume 6, pages 473–474 (2009)Cite this article

To the Editor: Human genetic variation comes in a wide range of sizes, from single-nucleotide polymorphisms and very small insertions and deletions (indels) to ‘structural’ variants, in which large segments of the genome are inserted, deleted, inverted or duplicated. Recently several methods for the identification of both small-size indels (<10 base pairs (bp))1 and larger ones (>50 bp)2,3 from high-throughput sequencing have been developed. There should also be a large amount of ‘medium-sized’ variation: insertions and deletions of 10–50 nucleotides. Here we describe MoDIL, mixture of distributions indel locator, the first method to identify 20–50-bp indels from high-throughput sequencing data. MoDIL is available at http://compbio.cs.toronto.edu/modil/.

Most sequencing techniques allow for the generation of mate pairs (two reads at an approximately known distance (insert size)). Mate pairs are used to locate structural variants by comparing the distance between the mapped locations of the read pairs on a reference genome (mapped distance) and the known insert size. A large deviation implies a structural variant, whereas smaller differences are likely due to variance in clone sizes and hence are not considered by most methods2,3,4. This limits the resolution of the structural variation detection approaches to indels >50 bp. Although deviation by several mate pairs from the expected insert size is likely, in MoDIL we used the intuition that deviation of many mate pairs (even by a small number of nucleotides) is indicative of an insertion or deletion.

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Figure 1: Summary of the MoDIL algorithm and accuracy of indel size estimation.

References

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

    Article  CAS  Google Scholar 

  2. Hormozdiari, F. et al. Genome Res. (in the press).

  3. Korbel, J.O. et al. Genome Biol. 10, R23 (2009).

    Article  Google Scholar 

  4. Lee, S., Cheran, E. & Brudno, M. Bioinformatics 24, i59–i67 (2008).

    Article  CAS  Google Scholar 

  5. Mills, R.E. et al. Genome Res. 16, 1182–1190 (2006).

    Article  CAS  Google Scholar 

  6. Bentley, D.R. et al. Nature 456, 53–59 (2008).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We acknowledge Canadian Institutes of Health Research Catalyst grant to M.B. for funding, and Q. Morris and A. Valouev for useful discussions.

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Authors and Affiliations

  1. Department of Computer Science, University of Toronto, Toronto, Canada

    Seunghak Lee & Michael Brudno

  2. School of Computing Science, Simon Fraser University, Burnaby, Canada

    Fereydoun Hormozdiari

  3. Department of Genome Sciences, University of Washington and the Howard Hughes Medical Institute, Seattle, Washington, USA

    Can Alkan

  4. Banting and Best Department of Medical Research, University of Toronto, Toronto, Canada

    Michael Brudno

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  1. Seunghak Lee
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  2. Fereydoun Hormozdiari
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  3. Can Alkan
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  4. Michael Brudno
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Lee, S., Hormozdiari, F., Alkan, C. et al. MoDIL: detecting small indels from clone-end sequencing with mixtures of distributions. Nat Methods 6, 473–474 (2009). https://doi.org/10.1038/nmeth.f.256

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