See Evolgen for a field guide to seminar audiences

EVOLGEN has a great post on the people at your department seminar. It is worth checking out and bringing with you next time you go to a seminar. Even better than looking around — choose which one fits you the best. Up until a few years ago, I was definitely the pre-schooler

The pre-schooler: This dude uses the departmental seminar as his nap-time. He sits in the back, and when the lights go out, he’s nodding off faster than River Phoenix in My Own Private Idaho. Someone get this guy a good-night’s sleep.

I simply could not stay awake in any seminar so I would have to sit at the back. Now that I have kids, I am used to sleep deprivation and only rarely nod off in a seminar. I am no longer sure which one I am …

Calling Michael Ashburner – please start a blog

I just got done with reading Won for All by Michael Ashburner which came out a few years ago. This book discussed the sequencing of the Drosophila genome by Celera and is a fascinating read. The best part is the snarky, obsessive, and funny commentary by Ashburner on the players and the games they played in the course of this project. I know the book came out a while ago, but if there ever was a science author perfectly built for blogging it has to be Ashburner. So I am calling all science blog fans to try and find a way to get him to start a blog. Also – he is a big supporter of open access publishing … as can be seen in the videos below:

See also some other Reviews of the book:

How human rights work and microbial ecology are similar

The New York Times has a brief one page article in the Sunday Magazine on “The Forensic Humanitarian” In the article, Jim Giles describes the work of Patrick Ball, a statistician working on searching for evidence for war crimes. The work is clearly important. But what caught my attention was his method. Basically, he uses a form of mark-release-recapture statistics taken from ecology studies. In the article, Giles writes

To understand Ball’s accomplishments, you might start with the problem of counting rattlesnakes.

And then he goes on to describe how one can estimate how many rattlesnakes are in a population by marking ones that you find and then counting how many times you refind one you have marked previously. This is a method generally known as mark-release-recapture (e.g., see the Wikipedia entry here, which seems OK but I have not read too carefully).

Apparently, Ball uses a similar type of statistic to estimate the number of murders and/or deaths in particular areas, by looking for overlap among different reports of deaths.

What you say does this have to do with microbial ecology? Well, everything. Because one of the most common methods for estimating the number of microbial species in a sample is to use a gene survey method where one isolates DNA from environmental samples and then one looks in the DNA for multiple versions of a gene found in all species (the gene most commonly used is known as small subunit rRNA). The gene survey method is needed because appearance is not a robust method of identifying microbial species.

From the gene sampling data, one then compares each version of the gene to the others and counts how many times one sees the same form of the gene (suggesting that one has found two different cells of the same species). If one keeps seeing the same forms of the gene even with only a few samples, one would estimate there are few species in the sample. If one keeps seeing different forms of the gene, one would estimate there are many species in the sample.

Things that seem to be hidden – be the murders or populations of rattlesnakes or microbes – can still be studied with what the Times perfectly refers to as

“A statistical sleight of hand”

Forget McCain – the Real Problem in the New York Times – Adaptationism

Unlike McCain and his followers, generally, I really like the New York Times, especially the Science articles. But they do continuously irk me in one area – they repeatedly include lame adaptationistic evolutionary arguments. Now I am not the only person in the bloggersphere railing against people who say something MUST be adaptive simply because it is there (Larry Moran is the most persistent and interesting critic of adaptationism out there).

This week the Times has a doozy in the article on “Play” from the Sunday Magazine. In the article, Robin Henig writes

If play is an extravagance, why has it persisted? It must have some adaptive function, or at least a benefit that outweighs its cost, or it would have been winnowed out by the forces of natural selection.”

This is nearly a PERFECT adaptationistic line. And more importantly, it is simply not true. Some things persist in biological systems even when they have a cost that outweighs the benefit. And other things persist when they are neutral. Now I am not saying one way or another whether play has a benefit (the article is interesting and reasonably sound in many ways). But such statements as the one quoted above show a common misunderstanding of evolution. Evolution is NOT only about beneficial things persisting and detrimental ones going away. It is much more complex and interesting in fact. If you want to learn more about the perils of adaptationism, go to Larry Moran’s blog. He really has some good stuff on it. Or go to the great gurus themselves – Gould and Lewontin.

Some pics of the new treefall

http://picasaweb.google.com/s/c/bin/slideshow.swf

Harvard’s Moving To Open Access – Let’s Use this to Push for OA at other places

Well, Harvard is frequently criticized for being a bit conservtive in responding to new ideas and initiatives. But it seems that recently Harvard is more like a oceangoing yacht than an oil tanker. And yesterday, the New York Times reported on a proposed new initiative that could make Harvard a leader in the movement towards “Open Access” publishing.

The Times reports

“Faculty members are scheduled to vote on a measure that would permit Harvard to distribute their scholarship online, instead of signing exclusive agreements with scholarly journals that often have tiny readerships and high subscription costs.”

and

“Under the proposal Harvard would deposit finished papers in an open-access repository run by the library that would instantly make them available on the Internet. Authors would still retain their copyright and could publish anywhere they pleased — including at a high-priced journal, if the journal would have them.”

In my opinion, there is no doubt this is a smart move. Sure, there are some potential downsides to open access. Some journals do good things and they may have to reinvent themselves to continue to bring in revenue. But welcome to the 21st century. It is not like other industries – like music and TV and movies and electronics and so on – have not had to reinvent themselves.

And the result are in — Harvard approved the initiative (see here for example). Now – I think we should use this as an example to get other institutions to do the same thing. As reported in the Boston Globe, Harry Lewis a CS Professor at Harvard said:

“Harvard is in a unique position to do the right thing in the academic world,” he said. “In this case, I think others will be emboldened by Harvard to follow its lead, and the course of collective action will be greater than the course any individual school will take.”

I will do my best to get UC Davis to do the same thing, but given the animosity towards open access exhibited by our acting provost Barbara Horwitz, it may be a tough ride here. Fortunately, they are interviewing candidates for provost now and hopefully whomever they pick will be more supportive.

So – here is a call to others out there. Push for the same type of thing at your institution. I will be posting more on this in the coming days/weeks. Maybe collectively we can follow Harvard’s lead on this and make Universities more about what they are supposed to be about – spreading knowledge.

Creating Mitochondria and a sign that we need open peer review

Well, since everyone else is posting about this I figured I should too (see for example Steven Salzberg’s Blog, The Harvard Crimson, Pharyngula). If you have not heard yet, there is an article in the journal Proteomics that discussed how mitochondria must have been created by an intelligent designer.

For example on p8 the authors say:

“Alternatively, instead of sinking in a swamp of endless
debates about the evolution of mitochondria, it is better to
come up with a unified assumption that all living cells
undergo a certain degree of convergence or divergence to or
from each other to meet their survival in specific habitats.
Proteomics data greatly assist this realistic assumption that
connects all kinds of life. More logically, the points that show
proteomics overlapping between different forms of life are
more likely to be interpreted as a reflection of a single common
fingerprint initiated by a mighty creator than relying on
a single cell that is, in a doubtful way, surprisingly originating
all other kinds of life.”

Say what you want about the journal Proteomics but boy did they screw this one up. I think they probably should have caught this without much effort but who knows exactly what happened. In all fairness to them, it is possible for weird thin gs to slip through at any journal. Reviewers are busy. Editors are busy. Everyone is busy. How can we prevent this from happening again. There is a simple change we could make that would help. It is called Open Peer review. That is, if reviewers names were publicly attached to papers they reviewed, and their reviews were published, we would be less likely to see things like this happen. Then, if someone agrees to do paper review, they would be careful about it. Sure, we would probably have a harder time getting reviewers, but that would be better than publishing crap.

What are the risks with Open Peer review? Well, some people might feel afraid to criticize others especially people with power. Well, I find this sad. Scientists criticize our collaborators and friends ALL the time in private. Why not be public about it? Aren;t we supposed to be searching for the truth? If we are, shouldn’t we be willing to give our opinions in public forums?

Marco Island – Saving Some of the Best for Last

Well, the Marco Island AGBT meeting just wrapped up and I they definitely saved some of the best for the end. I do not have a ton of time but here are my favorites:

Stephan Schuster gave a funny, entertaining and interesting talk on mammoth mitochondrial genomics. He riddled the talk with funny stories and one liners about his efforts to sequence old DNA and to publish the results. He did a good job of showing why Roche-454 sequencing is quite ideally suited for studies of old DNA.

John Leamon from Raindance Technologies summarize some of their work on droplet based microfluidics. He showed videos of droplets moving through their system and showed how it sould be used for various digital PCR-like activities.

But it was the last talk of the whole meeting that really did blow my mind. It was from Steve Turner from Pacific Biosciences. He presented an overview of their sequencing technology as well as a tiny bit of data. Now, normally I am uninterested in marketing talks where little data is presented. But this talk was different. First, their technology clearly has enormous potential for revolutionizing the sequencing field. Basically, what they are doing is reading the activity of a DNA polymerase as it replicates a single DNA molecule and they do it in real time. He referred to this as using the DNA polymerase as a sequencing engine and then he took the crowd through the details of the technology and some of the modifications they have made to make it work better. I will try to post later with more detail on their methods.

No – they are not quite ready for prime time yet. But the potential is pretty absurd. I see two key major advantages of their method if it can be fine tuned to work well — (1) it is screamingly fast – because they let the polymerase do all the work in essence (2) it can potentially get long reads — right now he claimed they could do up to 1500 base pairs and theoretically it could go much higher. If they can get this to work with reads of 10,000 bases for example, this will completely reconfigure the field. No longer will one have to worry about the complexities of mapping short reads as with many of the current “new” methods. And the long reads, coupled with many molecules per run, plus the high speed, this technology is the first I have seen that has shown some results and that could really lead to the $1000 human genome. Again, not clear when/if they will be ready for release to the world so don’t hold off buying one of the other systems that currently work (i.e., Illumina, Roche, ABI Solid) if you want to do “next gen” sequencing. But this company is one to keep an eye on.

NOTE – SEE ALSO

Marco Island sequencing frenzy – are we getting lost in all the data?

So – the Marco Island meeting could be summed up as a sequencing frenzy. Everyone and their mother presented something about how the next generation sequencers are revolutionizing their work. People are using these systems (well, people are using mostly Illumina and Roche sequencers and some are using ABI Solid) to do all sorts of new things – RNAi, gene expression, methylation, mutations, population genetics, comparative genomics, metagenomics, infectious disease, etc etc etc.

Certainly, much of this new work is truly revolutionary. Sequencing has gotten so cheap, and so easy, relative to even 3-4 years ago, that it can be used in all sorts of new ways. And new developments in sequencing seem poised to happen too, to make sequencing even cheaper and even better. Sequencing will get even better for a few reasons.

First, the current players in the market (Roche, Illumina, and possibly soon ABI Solid) are improving both their systems and their informatics such that they are getting more and more robust and easy to use and producing more data (Roche for example presented details on how they can extend their sequence reads to ~350 base pairs mostly by software and reagent changes). Lots of companies can say “We have some sequencing system about ready to be introduced” And lots of them are doing this at this meeting. But there is nothing like having sequencers in the hands of scientists to really test how well they work and to really help push the development of the technology.

Second, it does seem like some competitors for Illumina and Roche are coming. ABI presented multiple results from ABI Solid technology that makes it seem like these systems are ready for prime time. Whether other systems are ready for prime time is unclear. Helicos presented what could be seen as data. It was disappointingly minimal on detail but though I am rooting for them, it was far from convincing. But the discussions in the hallway seemed to suggest that Helicos is getting close. And there are 5+ other players itching to get into the market (some of which are apparently presenting later today). Some will fail. Some will succeed. And as long as their are a couple of good systems, the competition will push further development and reductions in costs. Thus everyone at the meeting I talked to said basically the same thing — this is an exciting time in sequencing.

So – sequencing is getting better and cheaper. That certainly will be good in many ways. But there are some negative aspects to this frenzy. I see two in particular. The first, which was discussed extensively at the meeting, is that nobody is really prepared to deal with the sheer volume of data coming out of these new systems. Data storage, transfer and analysis will unquestionably be the rate limiting steps in turining the new sequence data into knowledge.

And this is the other negative aspect of the new frenzy. Right now there seems to be a mad rush to apply the new sequencing methods to everything under the sun. And the data piles up. And piles up. And the biology seems to have taken a back seat in some cases. Perhaps the bext example of this is exemplified by something Neil Hall pointed out yesterday to me. There has been almost no mention at this whole meeting of things related to function of genes. For example, I have not heard “gene ontology” once. I do not think I have even heard “annotation” once. Function and process have been replaced by terms like “systems biology” and “SNPs” and “networks” and “massively parallel.” We have in a way regressed in terms of treating organisms (or communities) as a black box. Fine scale detail has been lost in a sea of data. In a way, we have all become born again geneticists. And I do not mean to disparage genetics. But I mean the part of genetics that treats organisms as a bit of a black box and focuses just on transmission of traits. We need to find a way to not get lost in all the data. I am not sure how to do that, but when we do, then the full potential of the new sequencing methods will be realized.

Coolest Thing at Marco Island – The Polonator


Without a doubt, the coolest thing at AGBT/Marco Island is the Polonator. This is a new sequencing system build by Denaher Motion based on the polony method from George Church’s lab. Now I have no idea if this machine even works. And even if it works, I have no idea how useful it will be. But the idea is brilliant and appealing. They are trying to be an “Open Development” Massively High Throughput Sequencing system. By Open they mean, they will use open source software (and would love developers to help) and will use non proprietary reagents and supposedly try to make everything as cheap as possible. They will still make the main piece of equipment and I assume this is what they hope to make money off of.

I went to a showing in a room nearby the seminar room. There were many skeptics there. Most were concerned about the read lenght coming from the machine. But it should get better. And if the price is a lot less for reagents and the machine than anyone else’s system — this could be an important player in the market.

//www.youtube.com/get_player

See also