Next generation sequencing offers unparalleled genomic resolution, allowing users to discriminate between single bases of the genetic code. It can be generated at ever increasing speed and ever decreasing costs. By no means a saviour – able to answer any and all questions – it nevertheless plays a role in the generation of data to be mined. Today, it forms a crucial part of the scientist’s toolkit and makes a valuable contribution to the field of drug discovery.
Different next-generation sequencing technologies have different strengths and weaknesses. Some next-generation sequencing technologies, such as 454 Life Sciences owned by Roche, are no longer commercially available. Others are still in production, such as Life Technologies’ SOLiD platform and Ion Torrent’s semiconductor sequencing, but are not as widely used as Illumina, the current market leader.
New technologies for next-generation sequencing
There are two comparatively new technologies making inroads on the next-generation sequencing market, developed by Pacific Biosciences and Oxford Nanopore. Both technologies generate longer ‘reads’ of DNA than Illumina; where Illumina reads up to 300 bases, Pacific Biosciences’ DNA sequencing technology can read tens of kilobases of sequence in a single read. Although both companies produce instruments with a smaller output of data than Illumina’s highest yielding instruments, Pacific Biosciences expects to increase its throughput over the coming months. Like Pacific Biosciences, Oxford Nanopore’s MinION sequencer can also produce long reads of DNA, but has the additional benefit of being highly portable – a similar size to a mobile phone, it is run by plugging it into a laptop or desktop computer. Oxford Nanopore is in the process of developing and releasing two more instruments; the mid-sized GridION and the high-throughput PromethION.
Next-generation sequencing can also be used to support the later stages of drug discovery, such as clinical trials. The Oxford Nanopore MinION has the advantage that it could be directly taken to the patient, even when the patient is in a remote, resource-limited location. A further potential benefit is the automated sample preparation systems under development by Oxford Nanopore, such as its VoITRAX machine. Subject to regulatory approval for clinical use, this would enable preparation of DNA ‘libraries’ for whole-genome sequencing outside the laboratory environment.
An exciting new chapter
Next-generation sequencing looks set to begin an exciting new chapter in the field of drug discovery, but with caveats. The sequencing process itself must be bookended by other processes, thoughtfully planned, to obtain maximum value from the sequence data. Immediately apparent is the need for good quality, robust DNA extraction protocols, tailored to the organism or tissue being studied. A favourite catchphrase within the sequencing community is ‘rubbish in, rubbish out’ (or a variant with more informal language). Essentially, it is not possible to extract reliable results from poor starting DNA.