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GENETICS
Whole-genome shotgun assembly and comparison of human genome assemblies

Sorin Istrail ^a, Granger G. Sutton ^a, Liliana Florea ^a, Aaron L. Halpern ^b, Clark M. Mobarry ^a, Ross Lippert ^a, Brian Walenz ^a, Hagit Shatkay ^a c, Ian Dew ^a, Jason R. Miller ^a, Michael J. Flanigan ^a, Nathan J. Edwards ^a, Randall Bolanos ^a, Daniel Fasulo ^a, Bjarni V. Halldorsson ^a, Sridhar Hannenhalli ^a d, Russell Turner ^a, Shibu Yooseph ^a e, Fu Lu ^f, Deborah R. Nusskern ^f, Bixiong Chris Shue ^f, Xiangqun Holly Zheng ^f, Fei Zhong ^f, Arthur L. Delcher ^g, Daniel H. Huson ^f h, Saul A. Kravitz ^b, Laurent Mouchard ^f i, Knut Reinert ^f j, Karin A. Remington ^b, Andrew G. Clark ^k, Michael S. Waterman ^l, Evan E. Eichler ^m, Mark D. Adams ^f n, Michael W. Hunkapiller ^o, Eugene W. Myers ^p, and J. Craig Venter ^b q

^aApplied Biosystems, 45 West Gude Drive, Rockville, MD 20850; ^bThe Center for the Advancement of Genomics (TCAG), 1901 Research Boulevard, Suite 600, Rockville, MD 20850; ^fCelera Genomics, 45 West Gude Drive, Rockville, MD 20850; ^gThe Institute for Genomic Research (TIGR), 9712 Medical Center Drive, Rockville, MD 20850; ^kDepartment of Molecular Biology and Genetics, Cornell University, 227 Biotechnology Building, Ithaca, NY 14853; ^lDepartment of Mathematics, University of Southern California, 1042 West 36th Place, DRB 155, Los Angeles, CA 90033; ^mDepartment of Genetics, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106; ^oApplied Biosystems, 850 Lincoln Centre Drive, Foster City, CA 94404; and ^pComputer Science Division, University of California, 775 Soda Hall, Berkeley, CA 94720

Contributed by J. Craig Venter, December 8, 2003

We report a whole-genome shotgun assembly (called WGSA) of the human genome generated at Celera in 2001. The Celera-generated shotgun data set consisted of 27 million sequencing reads organized in pairs by virtue of end-sequencing 2-kbp, 10-kbp, and 50-kbp inserts from shotgun clone libraries. The quality-trimmed reads covered the genome 5.3 times, and the inserts from which pairs of reads were obtained covered the genome 39 times. With the nearly complete human DNA sequence [National Center for Biotechnology Information (NCBI) Build 34] now available, it is possible to directly assess the quality, accuracy, and completeness of WGSA and of the first reconstructions of the human genome reported in two landmark papers in February 2001 [Venter, J. C., Adams, M. D., Myers, E. W., Li, P. W., Mural, R. J., Sutton, G. G., Smith, H. O., Yandell, M., Evans, C. A., Holt, R. A., et al. (2001) Science 291, 1304–1351; International Human Genome Sequencing Consortium (2001) Nature 409, 860–921]. The analysis of WGSA shows 97% order and orientation agreement with NCBI Build 34, where most of the 3% of sequence out of order is due to scaffold placement problems as opposed to assembly errors within the scaffolds themselves. In addition, WGSA fills some of the remaining gaps in NCBI Build 34. The early genome sequences all covered about the same amount of the genome, but they did so in different ways. The Celera results provide more order and orientation, and the consortium sequence provides better coverage of exact and nearly exact repeats.

Data deposition: The sequences of the assemblies herein referred to as WGSA, CSA, and WGA have been deposited in the GenBank database (whole-genome assembly project accession nos. AADD00000000, AADC00000000, and AADB00000000).

^c Present address: School of Computing, Queen's University, Kingston, ON, Canada K7L 3N6.

^d Present address: Department of Genetics, University of Pennsylvania, 1409 Blockley Hall, Philadelphia, PA 19104.

^e Present address: The Center for the Advancement of Genomics (TCAG), 1901 Research Boulevard, Suite 600, Rockville, MD 20850.

^h Present address: WSI-Algorithmen der Bioinformatik, Universität Tübingen, Sand 14, 72076 Tübingen, Germany.

ⁱ Present address: Department of Computational Biology (ABISS), University of Rouen, 76821 Mont-Saint-Aignan Cedex, France.

^j Present address: Institute of Computer Science, Freie Universität Berlin, Takustrasse 9, D-14195 Berlin, Germany.

ⁿ Present address: Department of Genetics, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106.

^q To whom correspondence should be addressed. E-mail: jcventer{at}tcag.org.

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