[epistatic]

I work at a big medical center and totally agree. The doctors have little genetic training and most can't interpret a simple amplicon test, whole genome or exome no way.

The sequencing portion per sample is now the smallest, labor, prep, service contracts, etc. are higher. But to get to fastq is probably the cheapest portion. The highest cost is storage of the data, processing, analysis, and interpretation.

[matholomew]

I also agree with Tony, sample and library prep are killers.
But here again Illumina have a killer - Nextera since the bought EpiCenter, and it's automatable so lower personnel requirements.

That leaves informatics, thats still slow, but for diagnostics maybe they have less genome variation to look at and call.

[matholomew]

Think that this is the point were you are wrong. Clusters are not Illuminas killer tech. Its heir most serious limitation! Scanning billions of clusters is slow and takes expensive optics that are prone to failure.

Semi conductors are the killer tech here. They are much faster, scalable and so chap that you just trow your chip away after using it. Sure, we are not quite there yet. But you have to consider that Rothberg has kept all of his promises so far, shown us the machine and chips and will be shipping them to ealy access customers this spring. Ion Torrent will make the current illumina tech obsolete.

Optics: MiSeq & HiSeq2500.
Improved chemistry and optics, faster sequencing, still cheaper than IonTorrent, cheaper than it will be and better quality values.

Clusters: I'd rather cluster than emPCR and select, or rely on poison distribution for PacBio.

I do agree semiconductors are better, but thats not using 454 tech (IonTorrent) it's the nanopores that will take advantage and win with this.

Re IonTorrent keeping its promises on improvements. Yes true, but that's pretty easy at the moment, they are well within the proven 454 technologies envelope of several years ago! When they get closer to what 454 can do in read lengths etc. NOW then see them slow down.

Also as chips go from e6 to e8+ picowells the price will get higher per chip. And what happens to the quality values as they drop from 3 field-effect transistors to just 2 or even 1 just to squeeze more in?

[TonyBrooks]

Dont think we disagree here. Illumina sequencing is awesome, has improved a great deal and is clearly the best choice for most applications right now!

All that I am saying is that its not 1000$ genome awsome and probably wont be in the forseable future.

For research the $1000 genome is great. For clinical applications, you need to be looking at the $100 genome or maybe even the $10 genome if you have a public health service and are a trillion dollars in debt (like the UK is).

My experiences working in research is that the cost of sequencing is fine at the moment when using our Illumina machines. I'm not sure how many researchers would want to routinely do whole genomes as the analysis would be a bit challenging.

About 10-15% of the cost of any project we undertake comprise of sequencing. The remainder are split between staff and sample prep.
Bottom line: We need cheaper scientists and cheaper library prep kits!

[steinmann]

... IonTorrent/Proton will not compete $/bp with Illumina ... The killer tech that Illumina have is clusters, it scales so much faster and better than emPCR - thats why IonTorrent can't win and will remain for smaller centers.

Think that this is the point were you are wrong. Clusters are not Illuminas killer tech. Its heir most serious limitation! Scanning billions of clusters is slow and takes expensive optics that are prone to failure.

Semi conductors are the killer tech here. They are much faster, scalable and so chap that you just trow your chip away after using it. Sure, we are not quite there yet. But you have to consider that Rothberg has kept all of his promises so far, shown us the machine and chips and will be shiping them to ealy access customers this spring. Ion Torrent will make the current illumina tech obsolete.

[TonyBrooks]

I'm not saying it's a good thing either. I hope Illumina can remain out of the Roche's reach too.
It's taken Roche 4 years to go from 500bp to 700bp (and not too robustly if any of the XL posts on here are anything to go by). In the same time frame Illumina have increased their throughput approximately 1000 fold while a the same time driving down the costs.

[steinmann]

I would disagree here.

Dont think we disagree here. Illumina sequencing is awesome, has improved a great deal and is clearly the best choice for most applications right now!

All that I am saying is that its not 1000$ genome awsome and probably wont be in the forseable future.

[matholomew]

Hmm so so, I usually keep my glass topped up ;-)

So Tony what do you disagree with?

I believe like you that Illumina has continued to execute improvements, borne out by the 1Gb>1Tb per run progression from GA>HiSeq. I haven't seen Roche manage anything similar nor would I expect them to start.

I would however expect serious management changes, and I dont think that would be good. Initially, say 12-18months, it would be Ok, as Illumina have a lot of stuff in the pipeline that they can dish out when they want to e.g. when there is actually some competition. But as that runs out and the bets people leave...?

[TonyBrooks]

Roche have a history of overpaying for technology that, depending on you point of view is either at it's peak, or that they kill. I favor the later based on the rosetta inpharmatics, 454 and Nimblegen experiences. I suspect that Roche are too big and ungainly to be nimble as nothing seems to progress once they touch it.

SOLiD is dead, 454 is a Zombie, IonTorrent/Proton will not compete $/bp with Illumina, and PacBio is niche. The killer tech that Illumina have is clusters, it scales so much faster and better than emPCR - thats why IonTorrent can't win and will remain for smaller centers.

That leaves nanopores, of which Oxford Nanopore is probably the leader, and Roche would be able to snag an interest in at least the Exonuclease sequencing version through Illumina - possibly killing both SBS and Nanopore.

I hope this deal never happens.

I take it you're a "glass half empty" kinda guy ;-)

[TonyBrooks]

Yes, but the issue here is that there has been no real innovation from Illumina since the introduction of their first machine. There has been nothing but gradual improvements and doing more of the same stuff using a bigger and more expensive machine (HiSeq2000).

I would disagree here. I think there has been great innovation by Illumina. Each upgrade brings improved performance and reliability and increased output. RNA-Seq, ChIP-Seq and resequencing are now all common and affordable tools for the majority of researchers. Those kind of experiments are in the same ball park as microarrays are in terms of costs which was unthinkable when the first Solexa machines arrived.

It's the same with all technology (TV's, computers, mobile phones, sequencers, whatever) in that a basic model comes to market and then there are gradual improvements over time. However, you can only improve something so far before you need change the core technology (when it becomes available). This the reason why we're no longer running computers the size of rooms powered by valves, why we have nice flat screen TV's in our living rooms and why we can play Angry Birds on the way to work.

[matholomew]

Roche have a history of overpaying for technology that, depending on you point of view is either at it's peak, or that they kill. I favor the later based on the rosetta inpharmatics, 454 and Nimblegen experiences. I suspect that Roche are too big and ungainly to be nimble as nothing seems to progress once they touch it.

SOLiD is dead, 454 is a Zombie, IonTorrent/Proton will not compete $/bp with Illumina, and PacBio is niche. The killer tech that Illumina have is clusters, it scales so much faster and better than emPCR - thats why IonTorrent can't win and will remain for smaller centers.

That leaves nanopores, of which Oxford Nanopore is probably the leader, and Roche would be able to snag an interest in at least the Exonuclease sequencing version through Illumina - possibly killing both SBS and Nanopore.

I hope this deal never happens.

[Elcannibal]

People need to serioulsy remove their research vision of sequencing, 100$, 1000$, 10000$ of buffer, chip and enzyme cost to sequencing have nothing to do witha proper clinical execution. There is a lot more involved in clinical worth than the simple part of sequencing... Anyone talking Solid or Pac Bio in a clinical study have not worked in the diagnostic field... There is SIMPLY no way this type sample prep can be automated under a 501K FDA let alone 21 CFR 11 software implementation (Ion Torrent also needs work there but much better IMO). There also needs to be a clinical worth... Need we talk about service and manufacturing demands of clinical requirements ?

May I remind everyone that Roche is the only player to manufacture drugs, manufacture diagnostic molecular instruments and have a basic research entity... Makes a lot of sense.

Seriously, the cost of NGS could be zero $ today, there are still millions of dollars involved in proper clinical execution other than putting a drop on a chip...

[steinmann]

This is why constant innovation is important. I don't believe Illumina are out of ideas just yet. Roche/454 seem to be though.

Yes, but the issue here is that there has been no real innovation from Illumina since the introduction of their first machine. There has been nothing but gradual improvements and doing more of the same stuff using a bigger and more expensive machine (HiSeq2000).

As their technology relies on fancy optics and lasers it will always remain pretty expensive, slow and unreliable. They may offer the most bp per buck right now, but a clinical grade 1000$ or even 100$ genome using their current techology does not seem very realistic to me.

[GenoMax]

As far as the US is concerned, the "clinical sequencing" market is probably the all important one. If Illumina is close to getting regulatory approval for sequencing of clinical samples then that could be the real reason of this takeover bid.

[TonyBrooks]

Not many people know what Illumina have round the corner though. Details of the Oxford Nanopore collaboration is still sketchy.
Plus, Illumina still has some pretty useful IP that would be applicable to all the high throughput sequencing platforms.