Sequencing round-up 2018

The deluge of new sequencing approaches continues at a pace. It seems that you turn your back for five minutes and there’s a shiny new sequencing platform promising to deliver more for less. What is the current state of play in the sequencing world, and what developments in sequencing technology should we be keeping an eye out for in 2018?
Illumina
Market leader Illumina have consistently delivered new short-read sequencing platforms with increasing output, reducing the costs for most sequencing applications. Their Novaseq 6000 is the latest addition to their range, and given time this seems likely to replace other HiSeq platforms such as the HiSeq X and HiSeq 4000. There are various types of sequencing chemistry available, with the S4 chemistry promising to deliver a staggering 500+ Gb of data per lane, while the current S1 chemistry delivers a more modest 240 Gb per lane. As far as I know, most sequencing centres are still getting to grips with this machine, and it’s currently unclear whether the move to the rapid output of 2-colour SBS chemistry will compromise sequencing quality. Watch this space: Once up-and-running, this will be give the cheapest sequencing to date, and will greatly reduce the cost of whole genome sequencing.

The Illumina NovaSeq 6000 (Photo: Alex Twyford)


Two other developments from Illumina are the iSeq 100 Sequencing System, and the TruSeq Genotype Ne Kit. The iSeq 100 is a new benchtop sequencer, and does exactly as it should, taking up little space and allowing lab groups to routinely deliver moderate sequencing output. This type of sequencer seems more relevant to clinical research, but may appeal to the molecular ecologist with cash to spare (!), who might use it for pilot projects, small genome sequencing, and amplicons (Twyford 2016). The TruSeq Genotype Ne Kit allows researchers to sequence a modest number of individuals for a modest number of targeted SNPs. This will be great for studies that need to genotype large numbers of individuals.
The question on most people’s lips though, is when will Illumina finally move into the long-read sequencing market? The Illumina compatible 10x Genomics Linked-Read Sequencing is a move in this direction, and seems a promising approach for improving de novo genome assemblies (Jones et al. 2017). However, Illumina’s competitors are still way ahead in the long-read sequencing field…
Pacific Biosciences
PacBio platforms have always appealed because they produce long-read sequence data, and as a single molecule real time sequencer it can also be used for PCR-free applications. The latest offering from PacBio, the Sequel System, was an instant hit with the research community. The Sequel has 7x higher output than the previous platform, the RS II, which makes it much more cost effective. I’m not aware of any major new releases from PacBio for 2018, but as the initial teething problems with the Sequel become a thing of the past, and as new pipelines for handling long-read data continue to come out, expect to see PacBio data featuring heavily in new publications. I’ve already used this for a de novo plant genome assembly, and was thrilled to get a mean read length of c. 20Kb, and many reads over 50Kb.
Oxford Nanopore
The Oxford NanoPore MinION is a thing of great beauty. It’s the only widely available handheld sequencer, and brings us closer to the dream of real-time sequencing in the field. It also has many of the benefits of PacBio, such as being PCR-free and producing long sequence reads. Watch this space: Oxford Nanopore is expanding, and there is a whole portfolio of things to come, like the smartphone sequencer the SmidgION, and the single-test sequencer the Flongle. There’s also a whole cottage industry of folk trying to produce field kit for DNA extraction and library preparation to make field sequencing a possibility. Maybe 2018 will finally see portable extraction kits, PCR thermocyclers, and the like, that make this a reality.
BGI
Bejing Genomic Institute has the biggest sequencing centre on earth. That being said, BGI are relative newcomers to the hardware market. They have chosen to enter this field by competing directly with Illumina with their own short-read sequencing platform, the BGISEQ-500. An initial study suggests it may produce data of a comparable quality to Illumina (Mak et al. 2017). Watch this space: BGI don’t do things by halves, and if this sequencer takes off it could challenge Illumina’s market monopoly.

Sequencers at BGI Shenzhen (Photo: Alex Twyford)


Flamingos at BGI Shenzhen. One of which has been sequenced recently… (Photo: Alex Twyford)


Outlook
2018 promises to be an exciting year in the sequencing world. Many of the recently released products dramatically reduce sequencing costs to a level where it’s possible to produce population-genomic datasets within the budget of a typical small grant, or indeed a PhD. These technologies really will open up the world of whole genome sequencing for non-model systems.
Let me know anything I’ve missed: @alex_twyford
References
Jones S, Taylor G, Chan S, et al. (2017) The genome of the Beluga Whale (Delphinapterus leucas). Genes 8, 378. doi:10.3390/genes8120378
Mak SST, Gopalakrishnan S, Carøe C, et al. (2017) Comparative performance of the BGISEQ-500 vs Illumina HiSeq2500 sequencing platforms for palaeogenomic sequencing. GigaScience 6, 1-13. doi:  10.1093/gigascience/gix049
Twyford AD (2016) Will benchtop sequencers resolve the sequencing trade-off in plant genetics? Frontiers in plant science 7. doi: 10.3389/fpls.2016.00433
 

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