It's nice to see my piece on the Ion Torrent 318 chip get a lot of comments, as well as being tweeted and some additional comments at SEQAnswers. I love getting comments, especially those that constructively challenge my analysis.
Two commenters threw some cold water on my enthusiasm, pointing out that the 318 is not scheduled to be released until September, and then only to early access customers. I'll confess to not asking careful enough questions on the timing & letting my desires get ahead of me. Ion Torrent will need to deliver these chips on time and working at specifications in order for scientists to believe that there really will be the promised regular upgrades. MiSeq is vaporware at the moment also, but Illumina has a strong track record for rolling out instruments.
One commenter took me to task for suggesting that Ion Torrent will simply roll right over Illumina. I don't mean to suggest this will happen, only that Ion Torrent may offer a very stiff challenge. If the PGM chip upgrades, sample prep improvements and read length improvements come as promised, then the PGM may well march up through Illumina's product line. That's not to say Illumina will remain static; they have clearly demonstrated great skill at pushing their platform to amazing abilities. The MiSeq may offer a new path to greater performance; there has already been speculation over at SEQAnswers on possible paths forward. For example, will the faster cycle times mean an opportunity for longer read lengths (if the reagents are not stable over very long runs)? Will Illumina roll out a multi-flowcell version of the MiSeq, enabling very high-throughput rapid-turnaround sequencing? I'd put more money on the latter than the former. Another thread has surfaced rumors that a HiScan upgrade is imminent which will give it HiSeq-like capabilities; for groups running both arrays and sequencing this could be useful. How much denser can Illumina pack the flowcells? Only time will tell. But, as I pointed out before, longer reads will have limited impact on overall throughput if the two reads are overlapping (though accuracy may be improved).
On the other hand, I do see as excessive cynicism (bordering on editing the truth) that AGBT had only Ion Torrent talking about Ion Torrent; given that two talks (Bolen from NCI and Nusbaum from the Broad; the Bolen talk will apparently be at ABRF as well) described actual experiences. Granted, neither was really independent of the company. It is critical for Ion Torrent's reputation that data start appearing in public spaces, especially data from regular customers.
Ditto for the experimental protocols; one commenter had a question about amplicon sequencing which will be important for Ion Torrent's success. The sooner applications are adapted to the system, the sooner customers will be buying machines and chips. Of course, a great strategy IMHO would be to put some sequencers in the hands of genomics bloggers.
As far as the question of reads per chip increasing faster than the number of sensors per chip, my understanding is that Ion Torrent expects that better sensor loading and utilization. Again, how vaporous is this? That's hard to tell -- and why feedback from actual users is desperately needed.
On the question of amplicon and read length for Ion Torrent, those would seem to be different fish (though I don't have direct experience). Amplicon length will be a matter of the emPCR conditions. I'm unaware of any signal amplification in the 454 chemistry -- I thought the signal cascade was strictly linear. But, again that is outside my expertise and I would enjoy being educated on the subject.
With regard to whether emPCR can be converted from a liability to a non-issue, it's reasonable to be skeptical. But, it isn't obvious why emPCR can't be compressed in time (though I haven't done emPCR, so that's a stretch for me to comment on). In my discussion with them, they pointed to cutting the number of cycles as one time savings. In any case, how hard as anyone tried to really optimize emPCR for speed? Only on the 454 might it have been a serious concern, and the cost of a 454 run is not going to encourage many folks to push for many runs a day. On the other hand, I don't see it as "disingenuous" the comparison I made; I've been at a company that had techs running PCR (again, conventional not emPCR) day in and day out, and any company that runs production Sanger is in a similar boat. Indeed, any big SOLiD or 454 shop must do this as well. What will the nature of the new emPCR kit be? I have some speculations, but that's a whole 'nother post.
One other surprise today from Ion Torrent is the announcement that they have sequenced the genome of Intel co-founder Gordon Moore. One claim from this is that the coverage was more uniform than with other platforms. Obviously, either publication or release of the data is needed to vet this claim. Even if they used 318 chips, this was an expensive demonstration project (I don't know the actual coverage; I don't have a subscription to In Sequence) -- even at 10X coverage it would be $20K (retail) in chips. Apparently this was an exclusive for GenomeWeb's In Sequence, as Ion doesn't even seem to have a press release out. I hope they plan to publish this in a journal soon, or if not make the primary data available for further study.