PT - JOURNAL ARTICLE AU - Drmanac, Radoje AU - Sparks, Andrew B. AU - Callow, Matthew J. AU - Halpern, Aaron L. AU - Burns, Norman L. AU - Kermani, Bahram G. AU - Carnevali, Paolo AU - Nazarenko, Igor AU - Nilsen, Geoffrey B. AU - Yeung, George AU - Dahl, Fredrik AU - Fernandez, Andres AU - Staker, Bryan AU - Pant, Krishna P. AU - Baccash, Jonathan AU - Borcherding, Adam P. AU - Brownley, Anushka AU - Cedeno, Ryan AU - Chen, Linsu AU - Chernikoff, Dan AU - Cheung, Alex AU - Chirita, Razvan AU - Curson, Benjamin AU - Ebert, Jessica C. AU - Hacker, Coleen R. AU - Hartlage, Robert AU - Hauser, Brian AU - Huang, Steve AU - Jiang, Yuan AU - Karpinchyk, Vitali AU - Koenig, Mark AU - Kong, Calvin AU - Landers, Tom AU - Le, Catherine AU - Liu, Jia AU - McBride, Celeste E. AU - Morenzoni, Matt AU - Morey, Robert E. AU - Mutch, Karl AU - Perazich, Helena AU - Perry, Kimberly AU - Peters, Brock A. AU - Peterson, Joe AU - Pethiyagoda, Charit L. AU - Pothuraju, Kaliprasad AU - Richter, Claudia AU - Rosenbaum, Abraham M. AU - Roy, Shaunak AU - Shafto, Jay AU - Sharanhovich, Uladzislau AU - Shannon, Karen W. AU - Sheppy, Conrad G. AU - Sun, Michel AU - Thakuria, Joseph V. AU - Tran, Anne AU - Vu, Dylan AU - Zaranek, Alexander Wait AU - Wu, Xiaodi AU - Drmanac, Snezana AU - Oliphant, Arnold R. AU - Banyai, William C. AU - Martin, Bruce AU - Ballinger, Dennis G. AU - Church, George M. AU - Reid, Clifford A. TI - Human Genome Sequencing Using Unchained Base Reads on Self-Assembling DNA Nanoarrays AID - 10.1126/science.1181498 DP - 2010 Jan 01 TA - Science PG - 78--81 VI - 327 IP - 5961 4099 - http://science.sciencemag.org/content/327/5961/78.short 4100 - http://science.sciencemag.org/content/327/5961/78.full SO - Science2010 Jan 01; 327 AB - 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.