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The proliferation of large-scale DNA-sequencing projects in recent years has driven a search for alternative methods to reduce time and cost. Here we describe a scalable, highly parallel sequencing system with raw throughput significantly greater than that of state-of-the-art capillary electrophoresis instruments. The apparatus uses a novel fibre-optic slide of individual wells and is able to sequence 25 million bases, at 99% or better accuracy, in one four-hour run. To achieve an approximately 100-fold increase in throughput over current Sanger sequencing technology, we have developed an emulsion method for DNA amplification and an instrument for sequencing by synthesis using a pyrosequencing protocol optimized for solid support and picolitre-scale volumes. Here we show the utility, throughput, accuracy and robustness of this system by shotgun sequencing and de novo assembly of the Mycoplasma genitalium genome with 96% coverage at 99.96% accuracy in one run of the machine.

The observed and measured on-orbit performance of various aspects of the fine guidance sensors is presented and discussed in the light of the original requirements and predictions. The fine guidance sensors are shown to meet or exceed the original requirements concerning dynamic pointing errors, photometric repeatability, and moving-target tracking capability. Calibration accuracy has been sufficient for observations to date, and fine-lock acquisitions are approaching a 100% success rate. Improvements to the fine-guidance-sensor tolerance of telescope spherical aberration, the South Atlantic anomaly, and solar-panel vibrations have been made, and further improvements are expected.

Next-generation sequencing technologies are revolutionizing human genomics, promising to yield draft genomes cheaply and quickly. One such technology has now been used to analyse much of the genetic code of a single individual — who happens to be James D. Watson. The procedure, which involves no cloning of the genomic DNA, makes use of the latest 454 parallel sequencing instrument. The sequence cost less than US$1 million (and a mere two months) to produce, compared to the approximately US$100 million reported for sequencing Craig Venter's genome by traditional methods. Still a major undertaking, but another step towards the goal of 'personalized genomes' and 'personalized medicine'. The DNA sequence of a diploid genome of a single individual, James D. Watson, sequenced to 7.4-fold redundancy in two months using massively parallel sequencing in picolitre-size reaction vessels is reported. The association of genetic variation with disease and drug response, and improvements in nucleic acid technologies, have given great optimism for the impact of ‘genomic medicine’. However, the formidable size of the diploid human genome1, approximately 6 gigabases, has prevented the routine application of sequencing methods to deciphering complete individual human genomes. To realize the full potential of genomics for human health, this limitation must be overcome. Here we report the DNA sequence of a diploid genome of a single individual, James D. Watson, sequenced to 7.4-fold redundancy in two months using massively parallel sequencing in picolitre-size reaction vessels. This sequence was completed in two months at approximately one-hundredth of the cost of traditional capillary electrophoresis methods. Comparison of the sequence to the reference genome led to the identification of 3.3 million single nucleotide polymorphisms, of which 10,654 cause amino-acid substitution within the coding sequence. In addition, we accurately identified small-scale (2–40,000 base pair (bp)) insertion and deletion polymorphism as well as copy number variation resulting in the large-scale gain and loss of chromosomal segments ranging from 26,000 to 1.5 million base pairs. Overall, these results agree well with recent results of sequencing of a single individual2 by traditional methods. However, in addition to being faster and significantly less expensive, this sequencing technology avoids the arbitrary loss of genomic sequences inherent in random shotgun sequencing by bacterial cloning because it amplifies DNA in a cell-free system. As a result, we further demonstrate the acquisition of novel human sequence, including novel genes not previously identified by traditional genomic sequencing. This is the first genome sequenced by next-generation technologies. Therefore it is a pilot for the future challenges of ‘personalized genome sequencing’.

We describe a novel sequencing system with a 100-fold improvement in throughput over state-of-the-art capillary electrophoresis instruments. The apparatus uses a single 60×60 mm 2 fiber optic slide containing 1,600,000 individual 75 pL wells and routinely generates 25 million bases of sequence in one 4-h run. When applied to bacterial genomes, it achieves consensus accuracies of better than 99.99%, at an average 12-fold depth of coverage. A single library preparation is sufficient to sequence an entire genome. We describe here the components of this system, the sequencing of several bacterial genomes and their de novo shotgun assembly. We also discuss a few early applications of this system in comparative genomics and the sequencing of PCR-generated products. Based on current performance and modeling of the existing system, we predict that the system's inherent scalability will lead to two additional orders of magnitude improvement in throughput, possibly enabling routine sequencing of individual human genomes.

The three Fine Guidance Sensors (FGS's) of the Hubble Space Telescope (HST) have two principal functions: 1) providing an absolute pointing reference to the telescope pointing control system, and 2) serving as an astrometry instrument.

Nature 437, 376–380 (2005) In this paper, the second name of Chun Heen Ho was misspelled as He. In the earlier Corrigendum (Nature 439, 502; 2006) the surnames of Stephen K. Hutchison and Brian C. Godwin were misspelled as Hutchinson and Goodwin. In addition, in the Supplementary Information of the original paper, there were errors in the sequences of the DNA capture and enrichment primers, and in the formulation of emulsion oil.