Human genome sequencing using unchained base reads on self-assembling DNA nanoarrays.
Genome sequencing of large numbers of individuals promises to advance the understanding, treatment, and prevention of human diseases, among other applications. We describe a genome sequencing platform that achieves efficient imaging and low reagent consumption with combinatorial probe anchor ligation chemistry to independently assay each base from patterned nanoarrays of self-assembling DNA nanoballs. We sequenced three human genomes with this platform, generating an average of 45- to 87-fold coverage per genome and identifying 3.2 to 4.5 million sequence variants per genome. Validation of one genome data set demonstrates a sequence accuracy of about 1 false variant per 100 kilobases. The high accuracy, affordable cost of $4400 for sequencing consumables, and scalability of this platform enable complete human genome sequencing for the detection of rare variants in large-scale genetic studies.
Drmanac
Radoje
R
Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, CA 94043, USA. rdrmanac@completegenomics.com
Sparks
Andrew B
AB
Callow
Matthew J
MJ
Halpern
Aaron L
AL
Burns
Norman L
NL
Kermani
Bahram G
BG
Carnevali
Paolo
P
Nazarenko
Igor
I
Nilsen
Geoffrey B
GB
Yeung
George
G
Dahl
Fredrik
F
Fernandez
Andres
A
Staker
Bryan
B
Pant
Krishna P
KP
Baccash
Jonathan
J
Borcherding
Adam P
AP
Brownley
Anushka
A
Cedeno
Ryan
R
Chen
Linsu
L
Chernikoff
Dan
D
Cheung
Alex
A
Chirita
Razvan
R
Curson
Benjamin
B
Ebert
Jessica C
JC
Hacker
Coleen R
CR
Hartlage
Robert
R
Hauser
Brian
B
Huang
Steve
S
Jiang
Yuan
Y
Karpinchyk
Vitali
V
Koenig
Mark
M
Kong
Calvin
C
Landers
Tom
T
Le
Catherine
C
Liu
Jia
J
McBride
Celeste E
CE
Morenzoni
Matt
M
Morey
Robert E
RE
Mutch
Karl
K
Perazich
Helena
H
Perry
Kimberly
K
Peters
Brock A
BA
Peterson
Joe
J
Pethiyagoda
Charit L
CL
Pothuraju
Kaliprasad
K
Richter
Claudia
C
Rosenbaum
Abraham M
AM
Roy
Shaunak
S
Shafto
Jay
J
Sharanhovich
Uladzislau
U
Shannon
Karen W
KW
Sheppy
Conrad G
CG
Sun
Michel
M
Thakuria
Joseph V
JV
Tran
Anne
A
Vu
Dylan
D
Zaranek
Alexander Wait
AW
Wu
Xiaodi
X
Drmanac
Snezana
S
Oliphant
Arnold R
AR
Banyai
William C
WC
Martin
Bruce
B
Ballinger
Dennis G
DG
Church
George M
GM
Reid
Clifford A
CA
D001483:Base Sequence; D019295:Computational Biology; D003365:Costs and Cost Analysis; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D030561:Databases, Nucleic Acid; D015894:Genome, Human; D015698:Genomic Library; D005838:Genotype; D006239:Haplotypes; D016045:Human Genome Project; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D049329:Nanostructures; D036103:Nanotechnology; D021141:Nucleic Acid Amplification Techniques; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA / Q000191:economics / Q000295:instrumentation / Q000379:methods* / Q000592:standards; D012984:Software
D004247:DNA