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.
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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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DOI: https://doi.org/10.1038/nmeth.1286
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