Monday, September 21, 2015

Some observations from Single Cell Genomics 2015

Just got back from a really great conference on Single Cell Genomics at Utrecht in the Netherlands. The lead organizer, Alexander van Oudenaarden (my postdoc mentor) was an absolutely terrific host, with excellent speakers, a superb venue, and a great dance party with live music in an old church (!) to cap it all off.

Here are some observations on the field from a relative outsider:

1. Single cell genomics is becoming much more democratic. As the tools have developed, the costs and complexity have gone way down in terms of preparing the libraries of cells, and it seems like the field has achieved some degree of consensus on barcoding and molecular identifiers. The droplet techniques are particularly remarkable in terms of the numbers of cells, and look relatively inexpensive and easy to set up (we are close to having it working in our lab, and we just started a little while ago).

2. Meanwhile, the quality of the data overall seems to have increased. Earlier on, I think there was a lot of talk about how much better one method for e.g. single cell RNA-seq was than the other, and the question on everyone's mind from the outside was which one to use. Nowadays, it doesn’t seem like any one method leads to radically different biological claims than anyone else’s. That’s not to say that there aren’t any differences, but rather that there are fewer practical differences between methods that I could see, especially compared to a few years ago. Then again, I'm completely naive to this area, so I could be way off base here.

3. tSNE was everywhere. Very cool method! It's important to remember, though, that it's just a new-fangled projection method that tries to preserve distance. Can't necessarily ascribe any biological significance to it–it's just a visualization method to help look at high-dimensional datasets. I think most folks at the conference realize that, but perhaps people from outside might not know about that.

4. This was undoubtedly a technology meeting. That said, while the technology is still rapidly advancing, I feel that we have to start asking what the new conceptual insights one might get from single cell sequencing might be. I think this question is in the air, and I think some clever folks will start coming up with something, especially now that the methods are maturing. But it will require some deep thinking.

5. Along those lines, one thing that sort of bugs me is when people start their talk with a statement like "It is clear that ABC is important for the cell because of XYZ" as motivation for developing the method. Sometimes I would disagree with those statements. I think that it's important to really dig into the evidence for some phenomenon being important and present that fairly at the beginning of a talk.

6. At the same time, one amazing talk highlighted some actual, real, clinical personalized medicine using single cell sequencing. Now THAT is real-world impact. I’m don't think it’s published yet, but when it is, I’m pretty sure you’ll hear about it.

7. Imaging is making a comeback. For a while, I was sort of bummed that sequencing was the new hotness and imaging was old and busted. But Long Cai and Xiaowei Zhuang showed off some very nice recent results on multiplexing RNA FISH to get us closer to image-based transcriptomics. Still a ways to go, but it has a number of advantages, spatial information of course being the most obvious one, sensitivity being another. One big issue is cost reduction for oligonucleotides, though. That may take some creative thinking.

8. This field has a lot of young, energetic people! As Alexander remarked, the poster session was huge, and the quality was very high. Clearly a growth area. It is also clearly friendly but rather competitive. At this stage, though, I think the methods are all sort of blending together, and I get the sense that the big game have already been hunted in terms of flashy papers purely based on methods. So maybe the competitiveness will diminish a bit now, or at least transfer elsewhere.

9. Speaking of growth, Dutch people are indeed really tall. Like, really tall. I had to use the kids urinal in the bathroom at the airport when I got off the plane.

Next year this meeting will be at the Sanger Institute–should be fun!


  1. Sounds like a great meeting.
    Did anyone discuss what is the lower threshold for single cell transcriptomics these days? (by RNA-seq) I mean, what is the minimum number of transcripts that can be detected with reasonable confidence?
    Ido Amit once told me that the lower limit is ~20 molecules/cell but that was a year ago.

    1. I think the field is sort of settling on 10% being the maximal recovery one can get. Some folks were claiming 2-3 mRNA per cell, but I feel like I would need to be convinced. May also be species dependent. The sensitivity is definitely a concern, I think.