title: High-quality draft assemblies of mammalian genomes from massively parallel sequence data.
abstract: Massively parallel DNA sequencing technologies are revolutionizing genomics by making it possible to generate billions of relatively short (~100-base) sequence reads at very low cost. Whereas such data can be readily used for a wide range of biomedical applications, it has proven difficult to use them to generate high-quality de novo genome assemblies of large, repeat-rich vertebrate genomes. To date, the genome assemblies generated from such data have fallen far short of those obtained with the older (but much more expensive) capillary-based sequencing approach. Here, we report the development of an algorithm for genome assembly, ALLPATHS-LG, and its application to massively parallel DNA sequence data from the human and mouse genomes, generated on the Illumina platform. The resulting draft genome assemblies have good accuracy, short-range contiguity, long-range connectivity, and coverage of the genome. In particular, the base accuracy is high (≥99.95%) and the scaffold sizes (N50 size = 11.5 Mb for human and 7.2 Mb for mouse) approach those obtained with capillary-based sequencing. The combination of improved sequencing technology and improved computational methods should now make it possible to increase dramatically the de novo sequencing of large genomes. The ALLPATHS-LG program is available at http://www.broadinstitute.org/science/programs/genome-biology/crd.
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Sante
authors.initials: S
authors.lastname: Gnerre
authors.forename: Iain
authors.initials: I
authors.lastname: Maccallum
authors.forename: Dariusz
authors.initials: D
authors.lastname: Przybylski
authors.forename: Filipe J
authors.initials: FJ
authors.lastname: Ribeiro
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Burton
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Walker
authors.forename: Ted
authors.initials: T
authors.lastname: Sharpe
authors.forename: Giles
authors.initials: G
authors.lastname: Hall
authors.forename: Terrance P
authors.initials: TP
authors.lastname: Shea
authors.forename: Sean
authors.initials: S
authors.lastname: Sykes
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Berlin
authors.forename: Daniel
authors.initials: D
authors.lastname: Aird
authors.forename: Maura
authors.initials: M
authors.lastname: Costello
authors.forename: Riza
authors.initials: R
authors.lastname: Daza
authors.forename: Louise
authors.initials: L
authors.lastname: Williams
authors.forename: Robert
authors.initials: R
authors.lastname: Nicol
authors.forename: Andreas
authors.initials: A
authors.lastname: Gnirke
authors.forename: Chad
authors.initials: C
authors.lastname: Nusbaum
authors.forename: Eric S
authors.initials: ES
authors.lastname: Lander
authors.forename: David B
authors.initials: DB
authors.lastname: Jaffe
mesh_terms: D000465:Algorithms; D000818:Animals; D016678:Genome / Q000235:genetics; D023281:Genomics / Q000379:methods*; D006801:Humans; D020407:Internet; D051379:Mice; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA / Q000379:methods*; D012984:Software