Sequencing technologies: past, present and future
- Over four decades ago, Frederick Sanger and his colleagues developed a method to decode the genetic information stored in DNA.
- The capillary sequencing method allowed the sequencing of the 1st human genome and, although it is labour intensive, it still remains today’s gold standard in terms of accuracy.
- Since the 1st human genome, the cost and turnaround time to sequence one human genome, or even several genomes in parallel, has dropped extraordinarily, far more than anyone predicted.
- This rapid development was made possible in the early 2000s by two main factors: a new generation of high throughput sequencing technologies referred as second generation sequencing, and the rapid development of computing power.
- Second generation sequencing had a straightforward sample preparation process and a high parallelisation of the sequencing process – in other words, it sequenced many short DNA strands at the same time.
- Machines produced by the biotechnology company Illumina became the best known on the sequencing market with its “$1000 dollars genome”.
- From 2010 onward, a third generation of sequencers emerged led by PacBio and Oxford Nanopore Technology (ONT). Both of these technologies use single-molecule sequencing and allow us to decode much longer stretches of DNA fragments, also called long reads.
- Although these new machines are more expensive and were initially less accurate than previous sequencing technologies, the benefits of long reads lie in their name. Just as a jigsaw puzzle with a few large pieces is much easier to solve than one with many small ones, assembling a genome is much easier with long read data.
- During the last decade, 3rd generation sequencers have improved greatly and they now compete with the previous generation sequencers in terms of accuracy (data quality).
- Their cost remains high but the (extra-)long reads they produce are extremely useful when we want to sequence species never sequenced before.
- Some of the 3rd generation sequencers are no bigger than a smart phone, and were even used on board of the International Space Station.
- Thanks to this rapid boost in the sequencing world, sequencing technologies can now be introduced into hospitals, or used for very large-scale projects such as the surveillance of the Covid-19 pandemic.
|Generation||1st generation sequencing||Next generation sequencing (NGS)||Future Generations|
|2nd generation||3rd generation|
|Technologies||Sanger sequencing (manual)||Sanger sequencing (automated)||
Article written by Louise Aigrain, Senior Staff Scientist in the DNA Pipelines Research and Development team” at the Wellcome Sanger Institute.
This page was last updated on 2021-12-14
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