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Sensitive, specific polymorphism discovery in bacteria using massively parallel sequencing

Nature Methods volume 6, pages 67–69 (2009)Cite this article

Abstract

Our variant ascertainment algorithm, VAAL, uses massively parallel DNA sequence data to identify differences between bacterial genomes with high sensitivity and specificity. VAAL detected ∼98% of differences (including large insertion-deletions) between pairs of strains from three species while calling no false positives. VAAL also pinpointed a single mutation between Vibrio cholerae genomes, identifying an antibiotic's site of action by identifying sequence differences between drug-sensitive strains and drug-resistant derivatives.

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Acknowledgements

We thank M. Borowsky, S. Young, J. Maguire, B. Cockerham and M. Grabherr for useful feedback during software development, I. Shlyakhter for providing computational infrastructure, T. Shea for validating tuberculosis reference differences, members of the Broad Institute Sequencing Platform for data generation, C. Russ for scientific project management, S. Gabriel and M. Zody for helpful comments, and the US National Human Genome Research Institute for support.

Author information

Author notes

  1. Toshiro K Ohsumi

    Present address: Present address: Department of Molecular Biology, Massachusetts General Hospital, Richard B. Simches Research Center, 185 Cambridge Street, CPZN-7250, Boston, Massachusetts 02114, USA.,

Authors and Affiliations

  1. Broad Institute of Massachusetts Institute of Technology and Harvard University, 320 Charles Street, Cambridge, 02141, Massachusetts, USA

    Chad Nusbaum, Toshiro K Ohsumi, James Gomez, John Aquadro, Deborah T Hung, Bruce W Birren, Eric S Lander & David B Jaffe

  2. Department of Science and Technology, Department of Biomedical Science, National Research Foundation Centre of Excellence in Biomedical Tuberculosis Research, Medical Research Council Centre for Molecular and Cellular Biology, Stellenbosch University, PO Box 19063, Tygerberg 7505, Cape Town, South Africa.,

    Thomas C Victor & Robert M Warren

  3. Department of Molecular Biology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, 02115, Massachusetts, USA

    Deborah T Hung

  4. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, 02139, Massachusetts, USA

    Eric S Lander

  5. Department of Biology, Massachusetts Institute of Technology, 31 Ames Street, 68-132, Cambridge, 02139, Massachusetts, USA

    Eric S Lander

  6. Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Alpert 536, Boston, 02115, Massachusetts, USA

    Eric S Lander

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  1. Chad Nusbaum
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Corresponding author

Correspondence to David B Jaffe.

Supplementary information

Supplementary Text and Figures

Supplementary Figure 1, Supplementary Tables 1–8, Supplementary Data, Supplementary Methods, Supplementary Results (PDF 554 kb)

Supplementary Software

VAAL source code and manual. (ZIP 836 kb)

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Nusbaum, C., Ohsumi, T., Gomez, J. et al. Sensitive, specific polymorphism discovery in bacteria using massively parallel sequencing. Nat Methods 6, 67–69 (2009). https://doi.org/10.1038/nmeth.1286

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