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Sunday, February 28, 2010

Complete Genomics, Revisited (Feb 2010)

While I'm writing up my notes on my way back to Vancouver, I thought I'd include one more set of notes - the ones I took while talking to the Complete Genomics team.

Before launching into my notes (which won't really be in note form), I should give the backstory on how this came to be. Normally, I don't do interviews, and I was very hesitant about doing one this time. In fact, the format came out more like a chat, so I don't mind discussing it - with Complete Genomic's permission.

Going back about a week or so, I received an email from someone working on PR for Complete Genomics, inviting me to come talk with them at AGBT. They were aware of my blog post from last year, written after discussing some aspects of their company with several members of the Complete Genomics team.

I suppose in the world of marketing, any publicity is good publicity, and perhaps they were looking for an update for the blog entry. Either way, I was excited to have an opportunity to speak with them again, and I'm definitely happy to write what I learned. I won't have much to contribute beyond what they've discussed elsewhere, but hey, not everything has to be new, right?

In the world of sequencing, who is Complete Genomics? They're clearly not 2nd generation technology. Frankly, their technology is the dinosaur in the room. While everyone else is working on single molecule sequencing, Complete Genomics is using technology from the stone age of sequencing - and making it work.

Their technology doesn't have any bells and whistles - and in fact, the first time I saw their ideas, I was fairly convinced that it wouldn't be able to compete in the world of the Illuminas and Pac Bios... and all the rest. Actually, I think I was right. What I didn't know at the time was that they don't need to compete. They're clearly in their own niche - and they have the potential to become the 300 pound gorilla.

While they're never going to be the nimble or agile technology developers, they do have a shot at dominating the market they've picked: Low cost, standardized genomics. As long as they stick with this plan - and manage to keep their cost lower than everyone else, they've got a shot... Only time will tell.

A lot of my conversation with Complete Genomics revolved around the status of their technology - what it is that they're offering to their customers. That's old hat, though. You can look through their web page and get all of the information - you'll probably even get more up to date information - so go check it out.

What is important is that their company is based on well developed technology. Nothing that they're doing is bleeding edge, nothing is going to be a surprise show stopper: of all of the companies doing genomics, they're the only one that can accurately chart the path ahead with clear vision. Pac bio may never solve their missing base problem, Illumina may never get their reads past 100bp, Life Tech may never solve their dark base problem, and Ion Torrent may never have a viable product. You never know... but Complete Genomics is the least likely to hit a snag in their plans.

That's really the key to their future fate - there are no bottle necks to scaling up their technology. We'll all watch as they bring down the distance between the spots on their chips, lower the amount of reagent required, and continue to automate their technology. It's not rocket science - it's just engineering. Each time they drop the scale of their technology down, they also drop the cost of the genome. That's clearly the point - low cost.

The other interesting thing about their company is that they've really put an emphasis on automation and value-added services. Their process is one of the more hands off processes out there. It's an intriguing concept. You fed-ex the DNA to them, and you get back a report. Done.

Of course, I have to say that while this may be their strength, it's probably also one of their weaknesses. As a scientist, I don't know that the bioinformatics of the field are well enough developed yet that I trust someone to do everything from alignment to analysis on a sample for me. I've seen aligners come and go so many times in the last 3 years that I really believe that there is value in having the latest modifications.
What you're getting from Complete Genomics is a snapshot of where their technology is at the moment you (figuratively) click the "go" button. Researchers like do play with their data, revisit it, optimize it and squeeze every last drop out of it - something that is not going to be easy with a Complete Genomics dataset. (They aren't sharing their tools..) However, as I said earlier, they're not in the business of competing with the other sequencing companies - so really, they may be able to side step this weakness entirely by just not targeting those people who feel this way about genomic data.

And that also brings me to their second weakness - they are fixated on doing one thing, and doing it well. That's often the sign of a good start-up company: a dogged pursuit of a single goal of excellence in one endeavour. However, in this one case, I disagree with Dr. Dramanac. Providing complete genomes is only part of the picture. In the long run, genomic information will have to be placed in the context of epigenetics, and so I wonder if this is an avenue that they'll be forced to travel in the future. For the moment, Dr. Drmanac insists that this is not something they'll do. If they haven't put any thought into it, when it does become necessary, it's something that will drive customers towards a company that can provide that information. Not all research questions can be solved by gazing into genomic sequences, and that's a reality that could bite them hard.

For the moment, at least, Complete Genomics is well positioned to work well with researchers who don't want to do the lab and bioinformatics tweaking themselves. You can't ask a microbiology lab to give up their PCR machine, and sequencing centres will never drop the 2nd (and now 3rd) generation technology lab to jump on board the 1st generation sequencing provided by Complete Genomics. Despite the few centres that have ordered a few genomes (wow.. I can't just believe I said "a few genomes"), I don't see any of them committing to it in the long run for all of the reasons I've pointed out above.

However, Complete Genomics could take over genomic testing for pharma or hospital diagnostics. Whoever is best able to identify variations (structural or otherwise) in genomes for the lowest cost will be the best bet to do cohort studies for patient stratification studies - and hey, maybe they'll be the back end for the next 23andMe.

So, to conclude, Complete Genomics has impressed me with their business model, and they have come to know themselves well. I'll never understand why they think AGBT is the right conference to showcase their company, when it's not likely to yield that many customers in the long run. But, I'm glad I've had the chance to watch them grow. Although they may be a dinosaur in the technology race, the T-Rex is still a fearsome beast, and I'd hate to meet one in a dark alley.



Anonymous Anonymous said...

Another concern is CG still produces 30-ish reads (so far as I know). This is not going to compete with the upcoming 100-1000bp reads by HiSeq, IonTorrent and PacBio. We will need more comprehensive assembly in future, not just local.

March 1, 2010 10:29:00 AM PST  
Blogger Anthony Fejes said...

That's also true. Currently, Complete Genomics only does short reads, but they are able to do PET, which should mitigate that particular problem for many applications... However, there's no reason to think they can't extend their read lengths in the future. It might require some modifications to their platform, but it could be done.

As well, since they only have one application, more than 95% of the genome problems they face probably won't really need longer reads. So, short reads are not as big a deal if they can mature their bioinformatics technology rapidly to get good coverage and accurate alignments. At any rate, as I tried to stress in the post, they're not going to compete with any of the long read machine vendors. Long reads are probably not going to be an asset in the majority of problems they're trying to tackle.

So, while I agree that their system isn't ideal or fancy, or even likely to be something I want to work with myself, (I'm a big fan of the pure biotech-type solutions, like PacBio or even the new Life Technologies stuff) I don't think we can write Complete Genomics off as easily as some people would like to believe.

Still, only time will tell. Forecasting the future accurately isn't something I have a lot of practice at.

March 1, 2010 10:48:00 AM PST  

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