A hybrid approach for the automated finishing of bacterial genomes

Ali Bashir, Aaron A. Klammer, William P. Robins, Chen Shan Chin, Dale Webster, Ellen Paxinos, David Hsu, Meredith Ashby, Susana Wang, Paul Peluso, Robert Sebra, Jon Sorenson, James Bullard, Jackie Yen, Marie Valdovino, Emilia Mollova, Khai Luong, Steven Lin, Brianna Lamay, Amruta JoshiLori Rowe, Michael Frace, Cheryl L. Tarr, Maryann Turnsek, Brigid M. Davis, Andrew Kasarskis, John J. Mekalanos, Matthew K. Waldor, Eric E. Schadt

Research output: Contribution to journalArticlepeer-review

149 Scopus citations


Advances in DNA sequencing technology have improved our ability to characterize most genomic diversity. However, accurate resolution of large structural events is challenging because of the short read lengths of second-generation technologies. Third-generation sequencing technologies, which can yield longer multikilobase reads, have the potential to address limitations associated with genome assembly. Here we combine sequencing data from second-and third-generation DNA sequencing technologies to assemble the two-chromosome genome of a recent Haitian cholera outbreak strain into two nearly finished contigs at >99.9% accuracy. Complex regions with clinically relevant structure were completely resolved. In separate control assemblies on experimental and simulated data for the canonical N16961 cholera reference strain, we obtained 14 scaffolds of greater than 1 kb for the experimental data and 8 scaffolds of greater than 1 kb for the simulated data, which allowed us to correct several errors in contigs assembled from the short-read data alone. This work provides a blueprint for the next generation of rapid microbial identification and full-genome assembly.

Original languageEnglish
Pages (from-to)701-707
Number of pages7
JournalNature Biotechnology
Issue number7
StatePublished - Jul 2012


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