Getting Ready for the Drosophila Conference...

Life's been busy lately as I frantically prepare to attend the 2011 Genetics Society of America Drosophila Research Conference in sunny San Diego, CA. We fly out on Wednesday morning, and I was informed only a few days ago that I will be presenting a brief talk summarizing our lab's work on the Model organism ENCODE (ModENCODE) project - something that I'll probably blog about in the near future, as papers are accepted and published.

I will however, also be presenting a poster on a side project that I hope to submit for publication relatively soon involving an interspecific comparative analysis of Unannotated Transcribed Elements detected in RNA-seq of Drosophila species. Here's an image of my poster, which can also be downloaded as a much more readable PDF by clicking on it:

Essentially, I've been looking at RNA-seq reads derived from transcripts expressed in both intronic and intergenic segments of the Drosophila melanogaster genome at various points over a 30 developmental stage time course (see Gravely et al. 2010). Are these transcripts noise generated by random genomic priming of RNA Polymerase II? Retained introns? Or perhaps some of them could be functional?

In order to address this, we've taken a comparative approach and looked at expression of these transcripts in other species (D. pseudoobscura and D. mojavensis, roughly 40 and 50 million years diverged, respectively): Many of them are also expressed at similar levels in those species as well. Furthermore, we've compared their levels of sequence divergence (between D. melanogaster and D. simulans, ~2.5 million years diverged) to randomly extracted coding exonic, intronic, and intergenic sequence. On average, these transcripts are more conserved than either intergenic or intronic sequence (but not quite as much as exonic sequence).

This is quite fascinating, and suggests that many of these transcripts may be functional (they also show signs of being regulated over the course of D. melanogaster development) and many of them are expressed primarily, or perhaps exclusively in males. Looks like there's still a lot about the Drosophila genome that we don't know, despite over 100 years of research1.

1Which is a good thing, or else I wouldn't have much to do!

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Update March 31st 2011: It seems that the PDF version of the poster wasn't downloading properly. This should be fixed now. 

Getting Old...

I believe that there comes a point in every young man's life, where he realizes that he's turning into his dad (and since my dad reads my blog, I hope he understands that I mean no offence!). You know what I mean: That point in your life where you look at some trend or aspect of the world, scratch your head, and admit that you just don't 'get it'. Consider the following: I found myself in need of some new pants, so I went to the store and tried on some jeans. I found a pair whose fit I liked and bought them... despite their being covered in holes:

This brand new pair of pants has been pre-torn, I can only guess to simulate that 'lived-in' feel?

Is this is what we've come to as a society? A people so lazy that we can't even be bothered to wear out our clothing through regular use? Where we fool each other into thinking that we actually bother to get dressed in the morning by buying pre-worn clothing? Or perhaps the clothing manufacturers have simply figured out a way to remove the middle man in the whole 'planned obsolescence' thing. There's nothing 'planned' about this: My new pants are already obsolete given that you typically buy new clothes once you get holes in the old ones.

I suppose that I am curious about one aspect of the whole pre-worn clothing phenomenon. Do clothes that are pre-worn dergrade more rapidly than those that are not? Or perhaps having already been imbued with holes, it makes it less likely that you'll notice new ones? Methinks there's the makings of an experiment here - something to give to an undergrad or something. I'd better write this down.

Sugarloaf Mountain, MD

One of the things that I've wanted to do more this year is go hiking. Though slightly difficult to do when one doesn't have a car, there are a number of different hiking 'societies' in the area (at least according to Meetup.com) that organize car pools and the like (there's actually one at the institute where I work, no less). While I'm still looking into these, I got the opportunity to go hiking with some friends this weekend on Sugarloaf "Mountain"1, Maryland. 

The area around Sugarloaf reminds me a lot of where I grew up, with lots of trees, farmland, and quaint 2-3 story houses. I suppose that there are trees and farmland everywhere, but I spend the overwhelming majority of my time locked firmly in the big city.

Though it seems a  little cold in the photograph, it was actually the perfect weather for hiking (10°C, 50°F): Not too cold, not too hot. We followed the 'blue' trail, which is fairly rugged 5 miles of rough rocky trail, with substantial changes in elevation. Not a cakewalk by any means, but rather a good workout.

Despite its rather modest elevation, Sugarloaf does have some great views of the countryside. Our entire drive through Pensylvannia felt almost exactly like this, perhaps with a few more rolling hills.

We ended up being a pretty large group of us in the end, which thankfully was not made up entirely of scientists! I sounds like a lot of folks in the area are quite into hiking, so I know I'm not alone. Thanks to Arnaud for the excellent photo!

So while I'm exhausted this evening after a long day of walking around in the woods, it was great! I'm busy as all hell with my work, but I think that it's nice to get away for at least one day of the weekend.

1I put mountain in quotations here because, having lived on the West Coast, I'm firmly in the 'real Mountains tend to have snow on them' camp. Sugarloaf's elevation is 1,282 feet (391 m), while Grouse Mountain, a small mountain in North Vancouver is 4000 feet (1200 m).

Computers in Science...

If all goes according to plan, I will be co-teaching a class this fall structured around topics in the analysis of genomes (genomics, transcriptomics, proteomics, and much more!). This will be part of a new 'section' or department of the small educational wing of our institution, focusing on genomics and bioinformatics - a field in which many people are apparently quite keen on gaining more experience. Interestingly, I was having a conversation with the organizer of this new section, and he told me that one of the core principles that he wants to convey with these new classes is an appreciation for the utility as well as practical challenges associated with computational biology (I'm paraphrasing of course).

If it were up to me, familiarity with Linux, PERL/Python, and R would be part of required classes for any honors major in the life sciences (and I'm sure that it would be useful in other sciences as well). We're quickly reaching a point where the ability to manipulate large datasets is unavoidable. Some labs cope with lack of such knowledge by hiring dedicated statisticians or computational research associates; but such an option isn't always available. Personally, I don't even like this route because it forces you to rely on someone else's knowledge (and potential to make mistakes) in order to interpret your own data. If this is unavoidable, then at least you should be very clear in terms of expectations of your ability to understand what was done1.

The sad fact of the matter is that the folks that I've met who are completely unfamiliar with computational work are sometimes either a) intimidated by it, and thus aren't particularly interested in learning about it, or b) overconfident in what computers can actually do. More troublesome is typically the latter, because it can lead to all kinds of mess. For instance, I once heard about a group of researchers that had generated a very large and very comprehensive dataset for a genome-wide association study of an interesting disease. They had assumed that they could analyze their data using their personal desktop computers, and thus had not left any room in their budget to purchase the sort of high-end clusters (or access to such computing power) that actually required to process such immense data.

As one of my former supervisory committee members was fond of saying: There are more possible alignments of 2 300 nucleotide DNA sequences than there are elementary particles in the known universe. Even modestly sized datasets (I realize that 'modest' is subjective) can take weeks to analyze on high-end desktop PCs. People who work with this kind of stuff day in and day out use much more powerful clusters of processors, designed for this type of work.

It's also important to keep in mind that a computer can only do what you tell it to do: Hence the famous garbage in/garbage out principle. If you cannot conceptualize the solution to a complex problem no amount of computational power is going to be able to provide said solution. At first glance, this appears laughably obvious - but unfortunately, it comes up more often than many of us would like to admit. I don't know how many times I've seen people generate huge datasets of say, expression data, and then expect a computer to find 'interesting patterns' in said data. 

Like any other science, computational biology is still about testing hypotheses. Computers are allowing us to test hypotheses that were previously out of reach, but they do not obviate the need to follow the scientific method.

1Collaboration is both a necessary and desired part of science - pooling together multiple minds of different backgrounds in tackling a project is almost always useful. However, I think it's important to keep a very clear picture in mind that collaboration should not be an assembly line: each participant should be reasonably familiar with all parts of the process. Nullius in verba!

Image cred here.

Rant: Amateur Public Performance...

Given the rough week I've been having1, it is high time that I bring back the venerable tradition of the online rant. Here it goes: There are a crazy number of people near my current home who like to either: 1) sing, 2) rap, 3) proselytize, or 4) listen to music without earphones in public places, particularly at bus stops and subway stations. I guess I've seen this stuff before - there are rude and/or crazy people everywhere you go, of course. However, the big difference between the places I've been and where I am now is the frequency of these occurrences: I'd estimate that I have to listen to someone's awful performance(s) ~2-3 times a week nowadays.

I really don't get it. Most of these people don't seem as though they're suffering from mental disabilities or anything like that. It's not people that are babbling to themselves about the apocalypse or begging for change. Instead, some normal-looking guy will walk onto the Metro train platform, stand around for a few seconds, and then break into a loud impromptu freestyle rap featuring all kinds of profanity. I've also heard little old ladies start belting out gospel at bus stops. One time, a rather large man began a completely undesired, one-sided loud conversation with another person waiting for the bus about how his faith in Jesus Christ was the only reason he wasn't out there killing people right now. As he explained it, Jesus was the only thing holding back the 'anger in his soul'.

Okay, I admit that that last one was 'hella' disturbing, and if I wasn't way out in the middle of nowhere setting up utilities for my apartment, I would've moved to another bus stop. But again, if most of these folks are sane, I can only assume that they're also incredibly rude. I don't care if you're an excellent singer, or if the music you're blasting out of your cell phone is great (occasionally it is something I legitimately enjoy), it's no cause to bother everyone around you. It also violates the first rule of public transportation: Keep quiet. There's a certain amount of ambient noise that's to be expected - conversations, traffic, etc. - but there's something especially aggravating about someone standing next to you shouting out some random off key tune.

And if anyone still thinks that this isn't annoying enough to warrant a rant, allow me to present exhibit A: The isolated vocal track of David Lee Roth singing Running with the Devil (1978). No seriously, compare it to the original Van Halen track. SEE?!?!?!?

1Every once in a while, you have one of those weeks where the work piles up faster than you can deal with it and nothing seems to work. Oh, I was also expecting this to be the first weekend I'd able to go biking in 3 months, but after spending an hour tuning up my bike, a spoke snapped the second I jumped on it. I brought it into the shop where I was informed that their work backlog is so big that I won't get it back for 2 weeks... Ungh.