title: Human genome sequencing using unchained base reads on self-assembling DNA nanoarrays.
abstract: 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.
authors.affiliation: Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, CA 94043, USA. rdrmanac@completegenomics.com
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authors.lastname: Drmanac
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mesh_terms: 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
chemical_list: D004247:DNA