>AGBT wrap up.

>So, everyone else has weighed in with their reviews of AGBT 2010 already, and as usual, I’m probably one of the last to write anything down. Perhaps the extreme carpel tunnel syndrome I’ve exposed myself to by typing out my notes should suffice as an excuse…

Anyhow, I wanted to put down a few thoughts on what I saw, heard and discussed before I forget what I wanted to say.

First off, I know everyone has commented on the new technologies already. I’m very disappointed that I wasn’t able to see the Ion Torrent presentation, and that I missed the presentation from Life Technologies. Those were two of the biggest hits, and I didn’t see either of them. While I did get a quick introduction on the Life Technologies platform from a rep in the Life Tech suite, it’s not quite the same.

However, I was there for several of the other workshops and launches, and in particular, the Pacific Biosciences workshop. In general, I think Pac Bio has been served up a lot of criticism for failing to disclose the exact error rate of their Single Molecule Real-Time (SMRT) sequencing platform, as well as for some of the problems they face. Personally, I’m not inclined to think of any of that as a failure – simply as engineering problems. Having worked on early 454 data, there were flaws that were equally disastrous as the challenges that Pac Bio now faces. Much of the criticism is simply directed at the fact that this is measuring single molecules of DNA, and not clusters. Clearly, there are will be challenges for them to overcome: The most obvious are that PacBio will have to lower the wattage of their light source and they’ll likely have to do some directed evolution (or even rational design) to lower the frequency at which bases are incorporated too quickly to be read, or possibly come up with a chemistry solution. (More viscous solutions? who knows.) All of the 2nd generation platforms were launched with problems – and Pac Bio certainly isn’t the exception to it. Each one gets better over time, and I’m certain PacBio will continue to improve. For the moment, they’ve suggested protocols like sequencing circular DNA that dramatically reduces the error rate, these issues aren’t nearly as big as the hype makes them out to be.

Just to finish off on the subject of SMRT sequencing, I think Elaine Mardis’ presentation on the results obtained with PacBio weren’t outstanding. Normally, I get really jealous about PacBio results, and wish that I could get my hands on some of them – but this time, I was left a little flat. While there are really neat applications for single molecule sequencing, Human SNPs really aren’t one of them. Why they chose to present that particular problem is somewhat beyond me. Not that the presentation was bad, but it failed to really showcase what the platform can be used for, IMHO. Their other presentations (SMRT Biology, for example), were pretty damn cool.

There has also been much talk about Complete Genomics, and how they’re not going to make it, which I’ve already written up in the previous post. I see that as a failure to understand their business model and to understand who they’re competing with (ie, not the other sequencing companies.) I expect that they’ll be the microarrays of the future – cheap diagnostic tools, with even better repeatability than your average microarray. I don’t think they should be written off just quite yet.

Finally, there has been much ado about the HiSeq 2000(tm), released by Illumina. While I have nothing against it (and am even looking forward to it), I don’t see it as much except for an upgraded version of their last machine, the GAIIx. They’ve changed the form factor and the shape of the flow cell, and then enabled some things that were previously disabled (such as two sided tile scanning), it’s really just an evolutionary change in a new box, which will allow them more room to grow the platform. Fair enough, really – I don’t know how many more upgrades you could put into one of their original boxes, but there’s nothing really new here that would have me running after them to get one. I should mention, however, that increased throughput and lower cost ARE significant and a good thing – they just don’t appeal to my geeky fascination for new technology.

Another criticism I heard was that these companies shouldn’t be calling their tech “3rd generation.” Frankly, I’ve been advocating since last year that they SHOULD be called 3rd generation, so that criticism seems silly, to say the least. Pyrosequencing is clearly synonymous with the 2nd generation of sequencing technologies, while Sanger sequencing is clearly first generation, and hybridization is kind of zero-th generation (although you could make a case for SOLiD being 2nd generation, which would also drag Complete Genomics into that group as well, then). However, the defining characteristic of 3rd generation, to me, is the move away from sequencing ensembles of molecules. An auxiliary definition is that it’s also the application of enzymes to do the sequencing itself. So, I’m just going to have to laugh at those who claim that 2nd and 3rd generation are all generically “next-generation” sequencing. There is a clear boundary between the two sets of technologies.

A topic I also wanted to mention was the use of technology at AGBT this year. Frankly, I was blown away by the coverage of all of the events through twitter. I enjoyed at least one talk where I left twitter open beside my text editor, and tried to keep notes while listening to the speaker had to say, while watching the audience’s comments. If I hadn’t been blogging, I think that would be the best way to engage. Insightful comments and questions were plentiful, and having people I respect discuss the topic was akin to having other scientists leave comments in the margins of a paper you’re reading. [Somewhat like reading Sun Tsu’s Art of War, where there are more annotations than original material, at some points.] Alas, it was too distracting to compile notes while reading comments, but it was really cool. Unfortunately, Internet coverage was spotty at best, and in some rooms, I wasn’t able to get any signal at all. The venue is great, but just not equipped for the 21st century scientist. Had I been there at the end of the conference, I would have suggested that perhaps it’s time to identify an alternate venue that can handle the larger crowds, as well as the technological demands of an audience that has 300+ laptop computers going at once. (Don’t get me started on electrical outlets.)

I’d like to end on a few good points.

The poster session was excellent – too short, as always, but the quality of the posters were outstanding, and I had fantastic conversations with a lot of scientists. I won’t mention them by name, but I’m sure they know who they are. I saw several tools I’ll try to follow up on. (By the way, if anyone was looking for me, I spent less than 20 minutes by my poster throughout the conference. There just wasn’t enough time to read all of them and still answer questions and absorb everything out there. Sorry about that – feel free to email me if you have questions.)

I should also mention that the vendors were all very hospitable. One of my enduring memories of this year will be Life Technologies allowing the Canadians to crash their suite and use one of their Demo TV’s to watch the semi-final Olympic hockey game. (Canada vs. Slovakia.) We were desperately outnumbered by non-Canadians, but they tolerated our screaming pretty well. (A few of them even seemed curious about this weird sport played on ice…) And, of course, anyone who saw my tweets knows about PacBio and the hawaiian shirt, just to name a few examples (-;

So, again, I think AGBT was a great success and I enjoyed it tremendously. Rarely in my life do I get to pack so many talks, discussions and networking into such a short period of time. It may have left me looking somewhat like a deer caught in the headlights, but unquestionably I’m already looking forward to what will be revealed next year.

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