Sunday, December 13, 2015
Cheese spread from the lab holiday party
Seriously awesome collection of cheeses from yesterday's lab holiday party! La Tur and Morbier (More Beer!) are some of my favorites, along with the brie Rohit brought. Eduardo's super stinky cheese was decent and definitely less funky tasting than smelling.
Blog hiatus (hopefully) over, and a few thoughts on writing grants
Had at least a couple folks ask why I haven’t written any blog posts lately. The answer is some combination of real-life work leading to writing fatigue and some degree of lack of inspiration. On a related note, writing grants sucks.
There have been some grants that I’ve had fun writing, but I would say they are in the distinct minority. I am of course not alone in that, but one of the reasons often trotted out for hating writing grants is that many scientists just hate writing in general, and I think that is true for a number of scientists that I know. Personally, though, I actually really like writing, and I typically enjoy writing papers and am reasonably fast at it, so it’s not the writing per se. So what is it that makes me leave the page empty until just days before the deadline while patiently waiting for the internet to run out of videos of people catching geoducks?
Part of it is definitely that grantwriting makes you sit and think about your work, how it fits into what we already know, and how it will tell us something new. It is certainly the case that grants can force you to critically evaluate ideas–writing is where weak ideas go to die, and that death can be painful. But I don’t think this is the whole story, either. I would say that the few grants I’ve really enjoyed writing are the ones where the process focused on thinking about the science I really want to do (or more likely already did) and explaining it clearly. So what is it about the other grants that make me try to find virtually any excuse to avoid writing them?
After a bit of reflection, I think that for me, the issue is that writing a grant generally often just feels so disingenuous. This is because I’m generally trying to write something that is “fundable” rather than what I really want to do. And I find it really REALLY hard to get motivated to do that. I mean, think about it. I’ve got to somehow come up with a “plausible plan” for research for 5 years, in a way that sounds exciting to a bunch of people who are probably not experts in the area and have a huge stack of applications to read. First off, if I ever end up in a situation where I’m actually doing what I thought I was going to do 5 years ago, I should probably be fired for complete lack of imagination. Secondly, the scope of what one typically proposes in a grant is often far less imaginative to begin with. Nobody ever proposes the really exciting thing they want to do, instead they just propose what reviewers will think is safe and reasonable. Not that these are some brilliant insights on my part; I think most applicants and reviewers are acutely aware of this, hence the maxim “An NIH grant should have 3 aims: 2 you’ve already done and 1 you’re never going to do”. So to the extent that everyone already knows all this, why do we bother with the whole charade?
I should say that I feel far less disingenuous writing “people” grants, by which I mean the fund-the-person-not-the-project grants like many junior investigator awards, HHMI and those as part of the NIH high-risk/high-reward program. At least there, I’m focusing more on the general area that we’re interested in in the lab, describing what makes us think it’s exciting, and why we’re well positioned to work on this topic, which is far more realistic than detailing specific experiments I’ll use to evaluate a particular hypothesis that I’ll probably realize is hopelessly naive after year 1. Of course, I think these are basically the criteria that people are judging “project” grants on as well for the most part, but at least I don’t have to pretend that I know what cell type I’m going to use in our RNA FISH validation studies in year 4… nor will I get dinged for a “bad choice” in this regard, either. This is not to say that writing people-grants is easy–it is particularly tricky to write confidently about yourself without sounding silly or boastful–but I’m just saying that the whole exercise of writing a people-grant involves writing about things that feel more aligned with the criteria by which I think grants should actually be evaluated.
(Sometimes I wonder if this whole system exists mainly to give people a way out of directly criticizing people. If you’re not too excited about a grant, can harp on technical issues, of which there are always plenty. I think this is an issue with our culture of criticism, which is probably a topic for another blog post.)
Carried a bit further, the logical conclusion to this line of argument is that we shouldn’t be judged on prospective plans at all, but rather just on past performance. Personally, I would much rather spend time writing about (and being judged on) science I actually did than some make-believe story about what I’m going to do. I remember a little while ago that Ron Germain wrote a proposal that was “people-oriented” in the sense that it suggested grants for all young investigators, with renewal based on productivity. His proposal engendered a pretty strong backlash from people saying that people-based grants are just a way to help the rich get richer (“Check your privilege!”). Hmm, don’t know that I’m qualified to delve into this too deeply, but I'm not sure I buy the argument that people-based grants would necessarily disfavor the non-elite, at least any more than the current system already does. Of course the current people-based grant system looks very elitist–it’s very small, and so naturally it will mostly go to a few elites. I don’t think that we can necessarily draw any conclusions from that about what people-based funding might look like on a broader scale. I also think that it might be a lot easier to combat bias if we can be very explicit about it, which I think may actually be easier in people-based grants.
As to the backlash against these sort of proposals, I would just say that many scientists have an inherent (and inherently contradictory) tendency towards supreme deification on the one hand and radical egalitarianism on the other. I think a good strategy is probably somewhere in between. Some people-based grants to encourage a bit more risk-taking and relieve some of the writing burden. Some project-based grants to keep programmatic diversity (because it would help fund important areas that are maybe not fashionable at the moment). I don’t know where this balance is, but my feeling is that we're currently skewed too far towards projects. For this reason, I was really excited about the NIH R35 program–until you follow this eligibility flowchart and find out that most roads lead to no. :(
Oh, and about the actual mechanics of writing a grant: my personal workflow is to write the text in Google Docs using PaperPile, then export to Pages, Apple’s little-used-but-perfect-for-grants word processing tool. The killer feature of Pages is that it’s SO much better than Word/Google Docs at allowing you to move figures to exactly where you want them and have them stay there, and as an added bonus, they will keep their full PDF-quality resolution. Only problem is that there are a grand total of around 18 people in the continental United States who use Pages, and none of them are writing a grant with you. Sad. Still better than LaTeX, though. ;)
Part of it is definitely that grantwriting makes you sit and think about your work, how it fits into what we already know, and how it will tell us something new. It is certainly the case that grants can force you to critically evaluate ideas–writing is where weak ideas go to die, and that death can be painful. But I don’t think this is the whole story, either. I would say that the few grants I’ve really enjoyed writing are the ones where the process focused on thinking about the science I really want to do (or more likely already did) and explaining it clearly. So what is it about the other grants that make me try to find virtually any excuse to avoid writing them?
After a bit of reflection, I think that for me, the issue is that writing a grant generally often just feels so disingenuous. This is because I’m generally trying to write something that is “fundable” rather than what I really want to do. And I find it really REALLY hard to get motivated to do that. I mean, think about it. I’ve got to somehow come up with a “plausible plan” for research for 5 years, in a way that sounds exciting to a bunch of people who are probably not experts in the area and have a huge stack of applications to read. First off, if I ever end up in a situation where I’m actually doing what I thought I was going to do 5 years ago, I should probably be fired for complete lack of imagination. Secondly, the scope of what one typically proposes in a grant is often far less imaginative to begin with. Nobody ever proposes the really exciting thing they want to do, instead they just propose what reviewers will think is safe and reasonable. Not that these are some brilliant insights on my part; I think most applicants and reviewers are acutely aware of this, hence the maxim “An NIH grant should have 3 aims: 2 you’ve already done and 1 you’re never going to do”. So to the extent that everyone already knows all this, why do we bother with the whole charade?
I should say that I feel far less disingenuous writing “people” grants, by which I mean the fund-the-person-not-the-project grants like many junior investigator awards, HHMI and those as part of the NIH high-risk/high-reward program. At least there, I’m focusing more on the general area that we’re interested in in the lab, describing what makes us think it’s exciting, and why we’re well positioned to work on this topic, which is far more realistic than detailing specific experiments I’ll use to evaluate a particular hypothesis that I’ll probably realize is hopelessly naive after year 1. Of course, I think these are basically the criteria that people are judging “project” grants on as well for the most part, but at least I don’t have to pretend that I know what cell type I’m going to use in our RNA FISH validation studies in year 4… nor will I get dinged for a “bad choice” in this regard, either. This is not to say that writing people-grants is easy–it is particularly tricky to write confidently about yourself without sounding silly or boastful–but I’m just saying that the whole exercise of writing a people-grant involves writing about things that feel more aligned with the criteria by which I think grants should actually be evaluated.
(Sometimes I wonder if this whole system exists mainly to give people a way out of directly criticizing people. If you’re not too excited about a grant, can harp on technical issues, of which there are always plenty. I think this is an issue with our culture of criticism, which is probably a topic for another blog post.)
Carried a bit further, the logical conclusion to this line of argument is that we shouldn’t be judged on prospective plans at all, but rather just on past performance. Personally, I would much rather spend time writing about (and being judged on) science I actually did than some make-believe story about what I’m going to do. I remember a little while ago that Ron Germain wrote a proposal that was “people-oriented” in the sense that it suggested grants for all young investigators, with renewal based on productivity. His proposal engendered a pretty strong backlash from people saying that people-based grants are just a way to help the rich get richer (“Check your privilege!”). Hmm, don’t know that I’m qualified to delve into this too deeply, but I'm not sure I buy the argument that people-based grants would necessarily disfavor the non-elite, at least any more than the current system already does. Of course the current people-based grant system looks very elitist–it’s very small, and so naturally it will mostly go to a few elites. I don’t think that we can necessarily draw any conclusions from that about what people-based funding might look like on a broader scale. I also think that it might be a lot easier to combat bias if we can be very explicit about it, which I think may actually be easier in people-based grants.
As to the backlash against these sort of proposals, I would just say that many scientists have an inherent (and inherently contradictory) tendency towards supreme deification on the one hand and radical egalitarianism on the other. I think a good strategy is probably somewhere in between. Some people-based grants to encourage a bit more risk-taking and relieve some of the writing burden. Some project-based grants to keep programmatic diversity (because it would help fund important areas that are maybe not fashionable at the moment). I don’t know where this balance is, but my feeling is that we're currently skewed too far towards projects. For this reason, I was really excited about the NIH R35 program–until you follow this eligibility flowchart and find out that most roads lead to no. :(
Oh, and about the actual mechanics of writing a grant: my personal workflow is to write the text in Google Docs using PaperPile, then export to Pages, Apple’s little-used-but-perfect-for-grants word processing tool. The killer feature of Pages is that it’s SO much better than Word/Google Docs at allowing you to move figures to exactly where you want them and have them stay there, and as an added bonus, they will keep their full PDF-quality resolution. Only problem is that there are a grand total of around 18 people in the continental United States who use Pages, and none of them are writing a grant with you. Sad. Still better than LaTeX, though. ;)
Saturday, December 12, 2015
Diet Coke vs. Coke Zero: Lab holiday party challenge!
A couple weeks ago, I was remarking how I like Coke Zero much more than Diet Coke, and Uschi said, "Oh, isn't it just the same thing, but just with a different label on it?" To which I responded "No way, it's completely different!" So we did a little blind taste test right there on the spot and I of course got them mixed up. :)
Ah, but that was just n=1. So with that in mind, we decided to take a more, umm, scientific approach at our lab holiday party today. Uschi set up two cups for all 13 participants, one with Coke Zero and one with Diet Coke. Everyone then had to say which they thought was which. Results? 11 of 13 got it right! (And I was one of them, thankfully...)
Verdict: Coke Zero and Diet Coke are distinguishable, with a p of 0.0017.
Ah, but that was just n=1. So with that in mind, we decided to take a more, umm, scientific approach at our lab holiday party today. Uschi set up two cups for all 13 participants, one with Coke Zero and one with Diet Coke. Everyone then had to say which they thought was which. Results? 11 of 13 got it right! (And I was one of them, thankfully...)
Verdict: Coke Zero and Diet Coke are distinguishable, with a p of 0.0017.
Monday, October 26, 2015
What happens if you think too much about RNA editing
This is what happens if you spend too much time thinking about RNA editing:
Don't let this happen to you.
PS: joking–I *love* editing. ;)
PS: joking–I *love* editing. ;)
Thursday, October 1, 2015
Fun new perspective paper with Ian Mellis
Wrote a perspective piece with Ian Mellis that just came out today:
http://genome.cshlp.org/content/25/10/1466.full
tl;dr: Where is systems biology headed? The singularity, of course... :)
(Warning: purposefully inflammatory.)
http://genome.cshlp.org/content/25/10/1466.full
tl;dr: Where is systems biology headed? The singularity, of course... :)
(Warning: purposefully inflammatory.)
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.
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.
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!
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!
Monday, September 7, 2015
Another option for how to shop your paper around
I had a very interesting conversation with a journal editor recently. Normally, when your paper gets solid reviews but gets rejected for “impact” reasons or whatever, the journal will try to funnel you into one of their family journals (“just click the link… just click the link…”). Good deal for them: they get to keep a solid paper, boost a new journal, maybe collect revenue from their open access honeypot, all without much additional work. Good deal for you? Maybe yes, maybe no. But here’s the thing the editor told me: if you got good reviews from some other journal, just take those reviews and send it in with your paper to our journal! Often, if there are no technical flaws, they can accept right away, maybe send for one additional reviewer just to double check. Sort of a personally-managed transfer.
There probably are some thorny ethical or legal issues with doing this, and I have not done it myself. Then again, my feeling, which is completely a guess based on anecdotes, is that some journals are increasingly sending out papers to review that they have no intention of publishing themselves, but want to capture into their family journals. (One thing is that it’s probably easier for editors to get good reviewers that way.) So I'm not sure anyone's hands are clean. Publishing is so demoralizing these days that I think you just do what you have to do.
Anyway, just another option to pass the time until a future of pre-print awesomeness arrives. Maybe we can then just send community feedback to the journal and be done with it!
There probably are some thorny ethical or legal issues with doing this, and I have not done it myself. Then again, my feeling, which is completely a guess based on anecdotes, is that some journals are increasingly sending out papers to review that they have no intention of publishing themselves, but want to capture into their family journals. (One thing is that it’s probably easier for editors to get good reviewers that way.) So I'm not sure anyone's hands are clean. Publishing is so demoralizing these days that I think you just do what you have to do.
Anyway, just another option to pass the time until a future of pre-print awesomeness arrives. Maybe we can then just send community feedback to the journal and be done with it!
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