An exciting new year

Now that both Life Technologies and Illumina have released their new generation of sequencers it seems that the fantomatic $1000 genome goal is suddenly at hand's reach. After the announcements made by both NGS leaders with two press releases yesterday, the new sequencers have been immediately at the center of the interest with many blogs, newspaper and commentaries (you can find lot of informations surfing on some of the blogs and sites we follow) speculating about the actual possibilities and future perspective of the new astonishing Ion Proton and HiSeq2500. So what can we say by now about these newborns?

Ion Proton

It relies on the same technology that boost IonTorrent PGM so it promises to be as fast and cheap (and of course with the same quality issues for homopolymers). It seems that the advancements are essentially based on larger chips (165M wells for the Ion Proton Chip I and 660M for the Chip II vs 11M wells on the 316 and 318 chips) and better materials for the semiconductor sensors.

The chemistry will also be the same of PGM. So it is expected that they will start with 2x200 bp pair end reads, even if the Ion Proton Chip I is announced for the mid-2012 and we think that the 400bp reads will be also ready to deliver at that time. In any case don't forget that, at this time, paired-end reads on IonTorrent are made by two overlapping reads (and not contiguous ones as for Illumina) so this greatly increase accuracy but not productivity.

Based on the actual standards for PGM (200 bp reads) we can speculate that the Proton Chip I (declared for exome) will deliver at least 12-14 Gb of sequences, so one can obtain a minimum of 2 exomes (considering the larger available exome kit by Agilent, about 70Mb) at about 90X or 3 exomes at a decent 50X. Since the Proton Chip II (declared for genome) contains 4 times more wells, we can suppose about 60 Gb of sequences (or they will follow the increasing curve of PGM chips with a 10-fold increase for every chip?), enough to get a single whole human genome at about 20X. You can see also predictions made in this post in the SeqAnswer forum (which are a little more optimistic than ours).

Now the costs: the Ion Proton machine itself costs about $ 150k (CEO of Life also announced dicounted prices for labs upgrading from PGM), but you have to consider also $ 75k for the Ion Proton Server necessary to run the machine and some more bucks for the Ion Proton OneTouch System (essential for library preparation). So we can think of an overall price of about $ 240k for a working platform. However don't forget that this system will include also the new analysis software developed by Life Technologies so there would be no need for additional computer equipment, at least at beginning (obviously we can say that for sure only with tech specifications for the new server available). The most discussed topic remains the actual cost of chips and of the entire workflow. In its press release Life Technologies stated a $ 1000 overall price for both Chip I and II, but most of the experts believe that this may be true for the Chip I (exome), but unlikely for the Chip II (genome), since rumors place the chip itself at $ 1000 cost. Will the $ 1000 genome remain out of grasp? We will see as Life releases tech specifications and commercial prices.

Addition considerations: nothing is known by now about compatibility between the new and the old instruments. Even if this is unlikely for the sequencer itself, it may result really useful for the side equipment like the OneTouch and the Server. The chemicals are though to be the same between the PGM and the Proton at least in this early phase. Another interesting question is: what's future now for the PGM? Speaking at the JP Morgan Healthcare conference yeasterday Life CEO Greg Lucier declared that he expect the PGM to continue to run side-by-side with the new proton since they answer to substantially different needs. They also assured that the development of the PGM technology will continue even if I personally think that they will improve read lenghts and chemicals but a new chip is unlikely to be developed. So the actual scenario is: PGM works fine for diagnostic (since it is fast cheap and really good on "small" targets), cancer (and other relatively small pre-made gene panels), compact genome applications (bacteria) and RNA-seq, while the new Proton is suitable for research applications based on exome and whole genome sequenching.

HiSeq2500 and new MiSeq

As for Proton, this new machine is based on the same chemicals and technology of the latest version and so promises to fullfill the same high quality standards. In this case advancements have been done in the cluster genertion and detection and adding the cluster generation procedure directly in the sequencing machine so that the entire procedure is quicker and more automated (like it is on the MiSeq).

The chemicals will also be the same, so it is expected that they will start with 2x150 bp pair end reads. But even in this case the 300 bp reads protocol seems to be almost ready and one can expect a rapid increase in productivity.

Illumina declared that the new instrument will come with a fast-run mode that produce 120 Gb of data (1 human genome at something more than 30X) in a 27 hrs run. However, even if this time is supposed to include the cluster generation done by the machine, you have to add some time for sample preparation. In the standard run mode the HiSeq2500 will produce 600Gb of data per flowcell in a 10 days run (about 5 genomes at 30X). CoreGenomics tried to estimate the cost per single genome concluding that it will be around 1000$ as for the Life new platform. Even more Illumina has already discussed the possibilities of 1Tb runs.

Coming to costs the HiSeq2500 will be sold at 720-740k $ and it is not clear to me if this price is for a ready-to-go package or some additional equipment is necessary for template preparation or data analysis. However Illumina have announced that luckly owners of the HiSeq2000 could upgrade to the new version for $50k, a pretty good deal.

Even more Illumina has made its move also in the field of benchtop sequencers, announcing susbtantial improvements in protocols and productivity for the MiSeq platform. They stated a 3-fold increase in sequencing throughput with a single run now producing 7Gb of data (enough for at least 1 exome at 100X). They also get 2x250 bp pair-end reads and a cycling 20 to 40% faster depending on applications (2,5 h for a microbial genome is declared in the press release).

Who is gonna win this battle?

Of course we all have to wait for further details to eventually declare a winner. However it is quite sure that the battle on the new NGS market has boosted innovation with great advantages for the final users!

By now I think that, with the new HiSeq2500, Illumina remains the leader in the field of large sequencers. Its platform has proved to produce really good an reliable results, even if the high cost place HiSeq out of the market for most research center of small and medium sizes. However it seems the best investment for large sequencing facilities, due to its huge productivity (1Tb in 10 days mean 100Gb/day/machine).

With its ultra fast and quite cheap platforms, the PGM and the new Proton, Life Technology has placed itself in a really good position for the "consumer" market (research centers and small labs interested in exome sequencing and WGS as well as diagnostic centers interested in mutations detection) . The Ion machines are also strong competitors against the Illumina's MiSeq, even more considering their semiconductor technology. This principle has shown some weaknesses in the past year, but surely still has a great potential in terms of flexibility and quick improvement.

Last, but not least, do not forget that there are some new companies, one for all Oxford Nanopore Technologies, that seem ready to come up with their 3rd generation platforms this year!