Whole-genome shotgun assembly and comparison of human genome assemblies.
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.
Istrail
Sorin
S
Applied Biosystems, 45 West Gude Drive, Rockville, MD 20850, USA.
Sutton
Granger G
GG
Florea
Liliana
L
Halpern
Aaron L
AL
Mobarry
Clark M
CM
Lippert
Ross
R
Walenz
Brian
B
Shatkay
Hagit
H
Dew
Ian
I
Miller
Jason R
JR
Flanigan
Michael J
MJ
Edwards
Nathan J
NJ
Bolanos
Randall
R
Fasulo
Daniel
D
Halldorsson
Bjarni V
BV
Hannenhalli
Sridhar
S
Turner
Russell
R
Yooseph
Shibu
S
Lu
Fu
F
Nusskern
Deborah R
DR
Shue
Bixiong Chris
BC
Zheng
Xiangqun Holly
XH
Zhong
Fei
F
Delcher
Arthur L
AL
Huson
Daniel H
DH
Kravitz
Saul A
SA
Mouchard
Laurent
L
Reinert
Knut
K
Remington
Karin A
KA
Clark
Andrew G
AG
Waterman
Michael S
MS
Eichler
Evan E
EE
Adams
Mark D
MD
Hunkapiller
Michael W
MW
Myers
Eugene W
EW
Venter
J Craig
JC
D019295:Computational Biology / Q000592:standards; D020451:Contig Mapping / Q000592:standards; D015894:Genome, Human; D016045:Human Genome Project; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis; D012984:Software
D012333:RNA, Messenger