Two complete cancer genomes were recently sequenced, one with each platform.36,37 Further rounds of innovation have yielded a diverse set of newer NGS methods. For instance, a number of “single-molecule” sequencing methods are now available or in development. These methods avoid the need to make thousands to millions of copies of DNA template molecules Inhibitors,research,lifescience,medical on microbeads or surfaces to assure that sequencing operations generate sufficient signal to read individual bases accurately, and instead use highly sensitive optics to detect bases at the single molecule level; this allows even denser packing of DNA templates and further efficiencies in sequencing chemistry. While Helicos
Biosciences has commercialized a singlemolecule considering system that simply arrays single template molecules on a surface and
uses sequencing cycle similar to the methods above, Pacific Biosciences is developing a system in which enzymes and templates are tethered to the bottom of nanofabricated wells Inhibitors,research,lifescience,medical and which monitors the signals generated by sequencing chemistry in realtime vs artificial cycles.38,39 Here, the nanofabricated wells enable substantially increased accuracy of single molecule base incorporation Inhibitors,research,lifescience,medical events. Finally, on another track, the company Complete Genomics, Inc has developed a method whereby very compact self-assembling amplicons of template DNAs called “nanoballs” are flowed onto a nanofabricated grid of ~300nm spots at 700 to 1300 nm Gemcitabine hydrochloride center-to-center distances. Three complete human genomes were sequenced with this method (as of January 2010) with an average consumable cost of $4400 and as low as $1500 for 40X coverage.40 Towards affordable personal Inhibitors,research,lifescience,medical genomes
These developments suggest that technology capable of Inhibitors,research,lifescience,medical meeting the cost target of $1000 or less for a diploid human genome sequence is within reach. Indeed, the indepth resequencing of individual human genomes has now been demonstrated several times by NGS developers to demonstrate that their methods have come of age. There are now published full genome sequences for at least seven individuals,40 with some having been sequenced by more than one method. There are also tens – and perhaps hundreds – of additional unpublished or partly published genomes (see, eg, refs 36,37), while the lower-coverage 1000 Genomes Project20,21 continues. Clearly, the age of personal genomics is now Drug_discovery close at hand. The PGP As described in the first section, one of the PGP’s central aims is to develop a publicly available, fully consented database containing comprehensive human genome and phenome data for its research participants. Such integrated datasets are fundamental drivers of progress in functional genomics and enable systems biology-based insights into the mechanisms of human health and disease.