Alright, it’s time to address the meat of the matter of AGBT; the state of play of sequencing technology. I’ll go through each of the major companies in turn, and talk about what they’ve brought to the table, and what the future holds for them.
As usual, for more in depth information you can follow me on twitter (@lukejostins). Other coverage can be found on Genetic Future, MassGenomics, Fejes, GenomeWeb and Bio IT World.
Illumina
I covered Illumina on day zero. Basically, the GAIIx can now generate 7Gb/day, with 2x150bp, and error rates universally under 2%. The HiSeq generates 31Gb/day, 2x100bp, with error rates under 1%; this will soon be pushed to 43Gb/day with a slight decrease in accuracy. For sheer volume of sequence, no-one can match Illumina.
454
As I said yesterday, 454‘s median read lengths are climbing into the 700-800 range, but with error rates being pretty high beyond 600 or so. Not bad, but after all the fuss over 1000bp reads, also a little disappointing.
454 have been pushing their work on assembly; they’ve worked pretty hard to make an easy-to-follow recipe, involving both single-end and paired-end sequencing, and the program Newbler. Many interesting critters have had this treatment, including bonobo, panda and Desmond Tutu (in order of majesty).
SOLiD
I found the SOLiD content of this conference very cool. Focusing more on the medical genomics side of things, SOLiD is involved in various clinical trials to see whether genomic information can increase cancer survivial times, and emphasizing the importance of accuracy in a clinical setting.
Lots of cool new tech too: For instance, mixing 2-base and 1-base encoding, apparently making error rates of 1 in 10^6 possible. Apparently library prep errors now dominate, so SOLiD has been working on finding more gentle enzymes for amplification. Particularly cool was a throw-away slide on running the ligase on single molecules and actually getting signal (though actual single-molecular sequencing probably isn’t economic).
Pacific Biosciences
Pacific Biosciences have produced an extremely interesting product; it is a game-changer, though exactly what it means for sequencing is not immediately obvious. I am going to hold back on writing about PacBio right now, because I have a more in-depth post on the exact specs and implications of the PacBio, in comparison to their nearest equivalent Oxford Nanopore, in the works.
Complete Genomics
Complete Genomics have gone from “interesting idea” to “thriving technology” in a very short period of time. They’re scaling up their sequencing centre as we speak; they’ll have 16 machines in the next few months, generating 500 40X genomes a month. Over the year, providing they get more orders, they’ll scale up to 96 machines, with a predicted 5X increases in capacity per machine as well. If this all goes well, in theory they are on target for their 5000 genomes by the end of the year.
Complete also have some very interesting new technologies on the horizon, which they will be discussing tomorrow; check the twitter feed for coverage. A lot of people underestimate Complete Genomics, but it is starting to become evident that they are as much game-changers as more flash technology.
Ion Torrent
Ion Torrent wins both my major awards this year: the “most surprising release” award and the “sounds most like a soviet weapons project” award. Ion torrent burst onto the scene with its tiny machine (GS Junior sized); the first major non-florescence-based method in a long time, using the emission of hydrogen ions from the the DNA polymerase reaction to measure incorporation in a 454 stylee.
The machine can produce a rapid 150Mb or so in a single hour run, for about $500 in disposables. The machine itself costs a tiny $50k. From what I’ve heard, a lot of people are interested in a machine like this for fast library validation, though it also has applications in diagnostics and microbiology. Unfortunately, it looks like the error rates are currently high, though they claim these will drop by release time.
Summary
Overall, we are starting to see a divergence in sequencing technologies, as each tech concentrates on having clearly defined advantages and potential applications that differ from all others. This means that the scientists themselves can more closely tailor their choice of tech to fit their situation. Are you a small lab that needs 10 high-quality genomes on a budget? Go to Complete. Want a cheap, fast machine for library validation? Use Ion Torrent. Setting up a pipeline for sequencing thousands of genomes? Go Illumina.
I suppose this was all driven by the fact that Illumina’s machine has such high yield that chasing them is a fool’s game, so everyone else is concentrating on what they can do that Illumina doesn’t. This is pretty good for science as a whole; we are moving away from the One-Size-Fits-All approach to high-throughput sequencing, and moving into a time of more mature, application-based methods.
The throughput improvements announced on the SOLiD platform appear set to make it competitive with Illumina by year-end…is it right to say Illumina’s dominance in that area is a given? Also, how much of a consideration are the much better accuracy for roughly similar throughput, and improvements in sample prep on SOLiD?
THAT WAS A REALLY A AMAZING INFORMATION
Thanks for taking the time to Blog this conference! Very useful.
Why the assumed dominance of illumina?. SOLID has similar throughput at a lower price from the data i have seen. Can you you put some figures on this. ?
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@NK and Neil Hall
You’re right, I shouldn’t dismiss the throughput of SOLiD, they do have some big improvements in the pipeline. However, I still don’t see SOLiD making inroads into Illumina’s dominance in sequencing centers.
Illumina claims yields of 200Gb in 8 days (25Gb/day) for the HiSeq, and SOLiD 4 claims 100Gb per run: they don’t say how long this takes, but SOLiD 3+ takes 12-14 days, so we’ll call it 8Gb per day.
Potential for growth: Illumina can raise its cluster density to that of the GAIIx with ease, bringing the throughput per day up to 43Gb/day. SOLiD will bring out the SOLiD 4 hq, which will produce 300Gb per run; assuming this doens’t raise the runtime (a very big if), this will bring their throughput up to a maximum of 25Gb per day.
You also need to think about Illumina’s massively longer read lengths (a maximum of twice the size now).
Not saying that SOLiD doens’t have other advantages. I just can’t really see SOLiD breaking Illumina’s market dominance, when Illumina has so consistently widened the gap in throughput over the past year, and shows no signs of stopping.
Hey was Panda sequenced by 454? Thought it was GAII.
Yeah you’re right, sorry about that.
How about running cost between HiSeq and SOLiD4hq?
@lamprey
According to Life, the SOLiD 4hq will be able to produce a 30X (100Gb) human genome for $3,000 in reagents (they also claim SOLiD 4 can do it for $6000); this doesn’t include library prep, but that is probably not very costly. If they can back this up with data (as the HiSeq has so far), then they will be able to push their price down below Illumina ($10k per genome, dropping to around $4k by the end of the year, though these include library prep)
Whether a) they can actually bring the price down as they say they can and b) this will be enough to persaude all the genome centers to completely change their pipelines to handle SOLiD machines and data, is still to be seen. I still can’t really see it happening, but I am starting to realise that I was too dismissive of SOLiD in this post.
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