title: A hybrid approach for the automated finishing of bacterial genomes.
abstract: 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.
authors: Pacific Biosciences, Menlo Park, CA.
authors: Ali
authors: A
authors: Bashir
authors: Pacific Biosciences, Menlo Park, CA.
authors: Aaron
authors: A
authors: Klammer
authors: Department of Medicine, Harvard Medical School, Boston, MA.
authors: William P
authors: WP
authors: Robins
authors: Pacific Biosciences, Menlo Park, CA.
authors: Chen-Shan
authors: CS
authors: Chin
authors: Pacific Biosciences, Menlo Park, CA.
authors: Dale
authors: D
authors: Webster
authors: Pacific Biosciences, Menlo Park, CA.
authors: Ellen
authors: E
authors: Paxinos
authors: Pacific Biosciences, Menlo Park, CA.
authors: David
authors: D
authors: Hsu
authors: Pacific Biosciences, Menlo Park, CA.
authors: Meredith
authors: M
authors: Ashby
authors: Pacific Biosciences, Menlo Park, CA.
authors: Susana
authors: S
authors: Wang
authors: Pacific Biosciences, Menlo Park, CA.
authors: Paul
authors: P
authors: Peluso
authors: Pacific Biosciences, Menlo Park, CA.
authors: Robert
authors: R
authors: Sebra
authors: Pacific Biosciences, Menlo Park, CA.
authors: Jon
authors: J
authors: Sorenson
authors: Pacific Biosciences, Menlo Park, CA.
authors: James
authors: J
authors: Bullard
authors: Pacific Biosciences, Menlo Park, CA.
authors: Jackie
authors: J
authors: Yen
authors: Pacific Biosciences, Menlo Park, CA.
authors: Marie
authors: M
authors: Valdovino
authors: Pacific Biosciences, Menlo Park, CA.
authors: Emilia
authors: E
authors: Mollova
authors: Pacific Biosciences, Menlo Park, CA.
authors: Khai
authors: K
authors: Luong
authors: Pacific Biosciences, Menlo Park, CA.
authors: Steven
authors: S
authors: Lin
authors: Pacific Biosciences, Menlo Park, CA.
authors: Brianna
authors: B
authors: LaMay
authors: Pacific Biosciences, Menlo Park, CA.
authors: Amruta
authors: A
authors: Joshi
authors: National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta GA 30333.
authors: Lori
authors: L
authors: Rowe
authors: National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta GA 30333.
authors: Michael
authors: M
authors: Frace
authors: National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta GA 30333.
authors: Cheryl L
authors: CL
authors: Tarr
authors: National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta GA 30333.
authors: Maryann
authors: M
authors: Turnsek
authors: Channing Laboratory, Brigham and Women's Hospital, Boston, MA.|Department of Medicine, Harvard Medical School, Boston, MA.|Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA.|Howard Hughes Medical Institute, Boston, MA.
authors: Brigid M
authors: BM
authors: Davis
authors: Pacific Biosciences, Menlo Park, CA.
authors: Andrew
authors: A
authors: Kasarskis
authors: Department of Medicine, Harvard Medical School, Boston, MA.
authors: John J
authors: JJ
authors: Mekalanos
authors: Channing Laboratory, Brigham and Women's Hospital, Boston, MA.|Department of Medicine, Harvard Medical School, Boston, MA.|Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA.|Howard Hughes Medical Institute, Boston, MA.
authors: Matthew K
authors: MK
authors: Waldor
authors: Pacific Biosciences, Menlo Park, CA.|Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York City.
authors: Eric E
authors: EE
authors: Schadt
mesh_terms: D000465:Algorithms; D001483:Base Sequence; D002771:Cholera / Q000235:genetics*; D019295:Computational Biology; D020451:Contig Mapping; D020459:Genes, rRNA / Q000235:genetics; D016680:Genome, Bacterial; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA / Q000379:methods*