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Friday, February 6, 2009

Complete Genomics, part 2

Ok, I couldn't resist - I visited the Complete genomics "open house" today... twice. As a big fan of start up companies, and an avid follower of the 2nd gen (and possibly now 3rd gen) sequencing, it's not every day that I get the chance to talk to the people who are working on the bleeding edge of the field.

After yesterday's talk, where I missed the first half of the technology that Complete Genomics is working on, I had a LOT of questions, and a significant amount of doubt about how things would play out with their business model. In fact, I would say I didn't understand either particularly well.

The technology itself is interesting, mainly because of the completely different approach to generating long reads... which also explains the business model, in some respects. Instead of developing a better way to "skin the cat", as they say, they went with a strategy where the idea is to tag and assemble short reads. That is to say, their read size for an individual read is in the range of a 36-mer, but it's really irrelevant, because they can figure out which sequences are contiguous. (At least, as I understood the technology.) Ok, so high reliability short reads with an ability to align using various clues is a neat concept.

If you're wondering why that explains their business model, it's because I think that the technique is a much more difficult pipeline to implement than any of the other sequencing suppliers demand. Of course, I'm sure that's not the only reason - the reason why they'll be competitive is the low cost of the technology, which only happens when they do all the sequencing for you. If they had to box reagents and ship it out, I can't imagine that it would be more significantly cheaper than any of the other setups, and probably much more difficult to work with.

That said, I imagine that in their hands, the technology can do some pretty amazing things. I'm very impressed with the concept of phasing whole chromosomes (they're not there yet, but eventually they will be, I'm sure), and the nifty way they're using a hybridization based technique to do their sequencing. Unlike the SOLiD, it's based on longer fragments, which answers some of the (really geeky, but probably uninformed) thermal questions that I had always wondered about with the SOLiD platform. (Have you ever calculated the binding energy of a 2-mer? It's less than room temperature). Of course the cell manages to incorporate single bases (as does Pacific Biosciences), but that uses a different mechanism.

Just to wrap up the technology, someone left an anonymous comment the other day that they need a good ligase, and I checked into that. Actually, they really don't need one. They don't use an extension based method, which is really the advantage (and achilles heel of the method), which means they get highly reliable reads (and VERY short fragments, which they have to then process back to their 36-to 40-ish-mers).

Alright, so just to touch on the last point of their business model, I was extremely skeptical when I heard they were going to only sequence human genomes, which is a byproduct of their scale/cost model approach. To me, this meant that any of the large sequencing centres would probably not become customers - they'll be forced to do their own sequencing anyhow for other species, so why would they treat humans any differently? What about cell lines, are they human enough?...

Which left, in my mind, hospitals. Hospitals, I could see buying into this - whoever supplies the best and least expensive medical diagnostics kit will obviously win this game and get their services, but that wouldn't be enough to make this a google-sized or even Microsoft-sized company. But, it would probably be enough to make them a respected company like MDS metro or other medical service providers. Will their investors be happy with that... I have no idea.

On the other hand, I forgot pharma. If drug companies start moving this way, it could be a very large segment of their business. (Again, if it's inexpensive enough.) Think of all the medical trials, disease discovery and drug discovery programs... and then I can start seeing this taking off.

Will researchers ever buy in? That, I don't know. I certainly don't see a genome science centre relinquishing control over their in house technology, much like asking Microsoft to outsource it's IT division. Plausible... but I wouldn't count on it.

So, in the end, all I can say is that I'm looking forward to seeing where this is going... All I can say is that I don't see this concept disappearing any time soon, and that, as it stands, there's room for more competition in the sequencing field. The next round of consolidation isn't due for another two years or so.

So... Good luck! May the "best" sequencer win.

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