AGBT previews...

LifeTech and ABI have been battling it out for supremacy in next-gen sequencing for the last four years. Traditionally the lead up to the AGBT (Advances in Genome Biotechnology) conference has seen the major sequencing companies announce their latest developments. It is always exciting and the last four years have seen GAIIx, HiSeq and MiSeq from Illumina as well as Helicos, Ion Torrent, and PacBio on the hardware front.

Announcements from both Life Tech and Illumina helped push their stock prices a little higher. I was surprised by both announcements but had been expecting them to release something before AGBT. Moving MiSeq technology onto HiSeq was not unexpected and many users had been asking if it would be possible.

These announcements certainly made a lot of noise and there are at least 100 news articles out at the time I write this.

The announcements: Proton vs HiSeq 2500
Life Technologies Proton: The Ion proton sequencer will give a $1000 genome in one day (nothing about the coverage of this genome though, or if it will use the new 400bp chemistry). The instrument will cost $150,000 and this will certainly make it affordable for many labs. The chips look about the same size as the PGM ones, there is a nice picture of Jonathan Rothberg holding one here. You can get more information over at Nick Loman's blog, "The Chip is (not) the machine".

Illumina’s HiSeq 2500: It did not take long for Illumina to catch up in developments today (the press releases were only hours apart), and I’d say outgun Life Technologies. The HiSeq2500 is a significant step forward for the platform and looks to give it another year or two of life. The big news on the press release was 120Gb in 27 hours! It sounds like the upgrade to HiSeq is going to include a few hardware changes ($50,000 has to go on something) and this appears to mean goodbye cBots and may also allow faster fluidics and imaging. Right now I’m not sure and will be digging for more information.

600Gb is the standard v3 output using paired end 100bp runs (although my lab has not quite made it that high so far, currently at just over 260Gb on our best flowcell). This run takes 10 days for a pair of flowcells and Illumina have already discussed 1Tb runs from more clusters on the lanes. Perhaps this will be the upgrade held in reserve until the end of the year?

600Gb per 2 flowcells costs under £20000 for 20 genomes at 10 fold coverage in 10 days, this is equivalent to 2 genomes per day at under £1000 per genome. OK so you have to wait ten days to get the genomes out the other end but who realistically needs their genome back in 24 hours, not a lot of users! And on HiSeq2500 you have a choice to do this anyway.

The ability to generate 120Gb of data in 27 hours suggests that chemistry is significantly sped up and that imaging will be limited to a few tiles per lane for this type of output. This will make the per Gb cost five times higher than a 600Gb run but data will be ready in just over a day.

The announcements: PGM vs MiSeq:
Life Technologies: There was no announcement on the PGM, although I believe some users are now testing the 400bp chemistry which is a nice improvement.

Illumina: The Miseq output has doubled (either another tile or dual imaging of the flowcell) and a new PE250bp kit configuration allows even longer runs. I know a group that has run some PE300 already by topping up the cartridges and we have done some single end 300bp sequencing on amplicons. The quality is good enough, but of course it always depends on your requirements.
Faster rune times will probably allow the PE250 to be completed in 27 hours keeping run times short.
It looks like 4-5Gb might come out of the instrument compared to the 1-2Gb from PGM.
A PE250 run will allow a 450-500bp amplicon to be completely sequenced.

Which companies machine(s) should I buy? I’d certainly agree that HiSeq has a high instrument cost compared to the Proton and many labs struggle with the $750,000 capital cost. However the cost of the genomes appears pretty comparable with Ion Torrents Proton instrument.And we should not forget that the capital cost of the instrument is only one consideration. Most users will be canny enough to weigh this carefully against all the other variables when making their choices.

It’ll be great when the users who are comparing Illumina and Ion Torrent publish some of their results. It is difficult to judge performance and which platform might be best when things are developing as fast as they are but this is the one piece of information users want to make purchasing decisions on. I’d guess a couple of high-impact publications one way or the other might swing sales of 100s of units.

PS: If BGI upgrade all their 137 HiSeq instruments they could theoretically generate 17.4Tb of data in just over one day using the fast run technology.

PPS: We should not forget Oxford Nanaopore Technology. Nearly everyone I know is expecting ONT to finally make an announcement that they have sequenced a genome. I hope it's a Human one but I'd be happy with PhiX!