More notes from Marco Island/ AGBT

Some notes on talks here:

My favorite talk yesterday morning was David Cox from Perlegen. He had as usual some good one liners including “Everybody and their mother is doing this so doing this is not so novel. What is novel about it is that it worked.” I should add that David Cox helped shape my career indirectly in many many ways. When I was a PhD student at Stanford, I got into genomics in part by teaching a course with David Botstein, Rick Myers and David Cox. When Craig Venter offered me a job at TIGR in 1998, I was not sure if moving to a non university was a good idea or not. So I asked many people for their opinions. Some said “You must do an academic post doc or you will never get a faculty job” I pretty much knew to ignore those folks. Cox gave the best advice. He said as long as I published things while at TIGR, it would not hurt me in any way. It probably would help. And so I took the job. And no doubt that was a great career move.

Other talks that were good were one by Joe Ecker, who discussed methylation in Arabidopsis and one by Andy Clark.

I skipped out on some of the lunch time to finish my talk for the PM session and also worked on my talk in the back of the room during the other PM talks. The PM session was on metagenomics and the most pleasing thing was that David Relman did not show up and he was replaced by Peter Turnbaugh from Jeffrey Gordon’s lab. Now – I wam not saying it was good that Relman was not there — he usually gives smashingly good talks. But Turnbaugh, a PhD student, stepped in as pinch hitter and gave a great talk on gut microbiome studies, really setting the stage for the whole session. I do not know if he was nervous stepping into a session like this but it did not show if he was. He certainly seemed relaxed when he said “Thanks to Dr. Relman for getting stuck in Chicago”

Forest Rowher gave a good talk on metagenomics and pointing out that viruses still get ignored in this field relative to their likely importance in communities. I have written about Forest before so I am going to discuss the other talks more … but if you have not heard him talk before try to find a way. He has a VERY different perspective on genomics and metagenomics than most of the people doing it. And he is dead right about the need to do more work on viruses.

Garth Ehrlich gave a talk on “bacterial plurality” and why he thinks gene content variation within communities of microbes in biofilms is important. His data certainly seemed solid and he showed some results that call into question the claims that some aspects of the “pangenome” hypothesis (he showed that the total number of genes in the Steptococcus strain collection does seem to level off after sequencing ~ 30 genomes and thus that the number of genes is not infinite as some people have suggested). So I liked some aspects of his talk. But he did make some evolution statements I found disagreeable (for those who care about the nitty gritty – he showed a cluster diagram of strain similarity and then used the position of strains within the cluster diagram to reflect relative branching order and historical patterns. A cluster diagram is a bad thing to use and one should use a phylogenetic tree for this. In addition he implied that one could make a genome-phylogeny from gene presence/absence information that would be more robust than a standard alignment phylogeny. This is not a reasonable thing
in my opinion — gene presence/absence patterns tend to end up grouping together unrelated lineages that have separately undergone gene loss. I just do not understand why people so badly want to not use alignments to build trees). Anyway – overall many of the things he said were interesting but I find certain non-evolution evolutionary analyses really grating.

Anyway – I was going to ask him a question after his talk about this, but then decided that, since I was talking next, getting into an argument with him just before my talk might seem lame. So I passed on the question. And then I gave my talk on the need to fill in the tree of life in terms of genome sequencing projects. I discussed a project we are just wrapping up that was part of the NSF “Tree of Life” program in which we sequenced genomes of eight bacteria that are from phyla that at the time had no genomes available. And then I talked about a new project I am coordinating at the Joint Genome Institute in which we are sequencing 100 genomes to really fill in some of the bacterial and archaeal tree. Next week I will post more about this project but I note – this is not done to study the tree of life per se. It is being done because if we have reference genomes from across the tree, all of our genome analyses of other systems and of metagenomes get better.

After dinner and some shell cllecting on the beach, there were evening talks and I went to the informatics session. Some of the talks there were good but the best thign I saw there was someone (I think Ben Blackburne) saying his slides were going to be on something called slideshare.net. I had never heard of this and checked it out and it seems pretty cool. I may use it in the future … but gotta go off to other things.

Marco Island Evening One – The Strange and the Good

Well, I made it through my talk at Marco Island without too many scars. It seemed to go pretty well – I talked about a new project in which I am involved at the Joint Genome Institute on creating a Genomic Encyclopedia for Bacteria and Archaea. I will write about that more here at another time.

But what I want to do now is discuss some of the marketing ploys from last night. One of the strangest was from the Pacific Biosciences group which sponsored a beach party with fireworks. It was completely surreal. People lingering at the beach with drinks and loud music and then all of a sudden – fireworks were launched into the sky. Not the “greenest” of activities I must say. But never mind that. What was the reason for fireworks in the middle of February? I guess the company is trying to make a big splash but the whole thing was just strange to me.

Much better was the party sponsored by Genome Technology magazine. It was a few hundred yards down the road at a bar. Everyone had to walk there which was good since many people end up never leaving the halls around the conference area. And the place was packed to the gills with people drinking and eating and seemingly having a good time. No fireworks (thankfully) and a good respite from the hotel.

Needless to say, these types of festivities do not happen at any evolution or ecology conference I have been to. The genomics world is still heavy on the marketing and self promotion. Sometimes that makes it fun (Genome Technology) and sometimes it just makes me want to run away (Pacific Biosciences).

AGBT Marco Usland Update – Long Live Sequencing

Well, I am sitting in the back of the room at the AGBT meeting and just heard Eric Green give the introduction and Joe Ecker is talking right now. And the theme of the meeting is pretty clear:
LONG LIVE SEQUENCING

Basically, the meaning of this is that, though many said sequencing was dead a few years ago, sequencing is alive, thriving, and going a bit crazy. With the new massively parallel high throughput sequencing machines sequencing is being used for everything and anything. For example, Ecker is using sequencing to study methylation of the genome of Arabidopsis. And others are usign sequencing for expression studies. And of course there is population genetics. And genetic mapping. And my favorite – metagenomics. And so on. So, despite the push to move into a “post genomics” world, sequencing is growing in use not shrinking.

Advances in Genome Biology and Technology Meeting – First Post

Well, I have just finally gotten online at the “Advances in Genome Biology and Technology Meeting” also known as the Marco Island Genome Meeting (because it is held in Marco Island in Florida), or, as we used to call it at TIGR when I worked there, the “I don’t want to go to Venter’s Genome Meeting Meeting”.

My flight in had some issues so alas I missed the workshop today on new technologies, and cannot report on that here, but I think I will get enough on the new technologies at the rest of the meeting to report later.

I got in to Ft Myers Airport at about 5 PM and took a shuttle bus ride from the airport to the Marriott on Marco Island. As usual, I blabbed away on the bus ride. Somehow, I always end up talking about my time at TIGR and my interactions with Craig Venter and Claire Fraser and my witnessing the fights between the Venter camp and the TIGR camp (if you do not know what I am talking about, feel blessed).

I checked in, dumped my bags and then went to the meeting registration where I got a free backpack full of meeting marketing material. Then I bumped into some colleagues and friends including Neil Hall, who was on the faculty at TIGR when I was there and has now moved back to the UK to Liverpool. I also saw Elaine Mardis, who was just at Davis giving a talk about new sequencing technologies (I missed her talk but took her out to lunch in Davis).

After ditching the backpack full of dead trees, I went to the reception/party by the pool. The food was not so bad, the drinks were free, and I bumped into many other colleagues, some of whom I have not seen in many years, and some who I should see more often (e.g., Chuck Langley, who is a colleague at Davis was there as was Len Pennacchio who is at the Joint Genome Institute where I have an Adjunct Appointment and where I try to spend some time, but alas, usually do not).

Anyway – I will post notes and pictures from the meeting as the days go by … I will try to do it in some regular manner but we will see how that goes.

Charles Darwin Endorses Obama as the "Natural Selection"

LONDON (AP).

Charles Darwin, famous for his work on the evolution of species, has announced that he is endorsing Sen. Barack Obama for President of the United States. Darwin through his family website said

“I have been watching the election in the States closely from my resting place. And though I like both Clinton and McCain in some ways, Obama is the clear choice from an evolutionary perspective.”

Darwin has not endorsed a political candidate since Churchill and has never weighed in on elections in the US. He went on to say

“With all the trouble in the US over evolution, they need a strong candidate that embodies what evolution is all about. In this respect he is the natural selection. He stands for change and for survival. Plus he is the strongest advocate for science among the bunch”

Representatives from the Clinton camp would not discuss the endorsement on the record but one who asked to not be named since they were not authorized to discuss the issue said

“You know, we tried to reason with Charlie about this. We even got Bill to send some messages his way. But in the end, there is no changing the minds of some people, especially the dead.”

Obama was thrilled. He said

“Since I was a little boy, I have been fascinated by dinosaurs. And I have carried that with me to today, where I am a strong supporter of having science education be independent of religion. I cannot think of a better person to get behind my candidacy.”

Other deceased scientists are also considering endorsing candidates but none had made an announcement as of press time.

Top Roles of Microbes in the Superbowl

Well, it is the time of year for everyone to hunker down and watch some good ads on TV in between football plays (I am a football fan, but most years, the ads are better than the game).

And in the spirit of microbiology education I have created a my list of some of the fun roles microbes will play in the superbowl.

  • Can anyone say HGH? Sure you can get it from grinding up cadavers, but it is a bit easier to get it from engineered bacteria.
  • Cleanliness is next to Godliness.With all the blood, grass, sweat, and other stuff from the Championship games, cleaning those uniforms is going to be tough. Better use some detergents with extra enzymes like these.
  • Victory celebration. To the victor goes the bubbly. And boy, that bubbly would really rot without microbes.
  • Making a good football. Without some serious processing, a cowhide or pigskin is not something you would want to throw around. Enzymes are a key part of most leather processing. And hey – who makes most of the best enzymes on the planet. That’s right, microbes.
  • Obesity epidemic. Sure, pumping iron and taking steroids will get you big. But maybe those linemen just have a health dose of some of Ruth Ley’s gut bacteria.
  • Avoid double dipping. MSNBC (and everyone else) is reporting this story. MSNBC says “Keep an eye on the salsa this Super Bowl Sunday: A researcher inspired by a famous “Seinfeld” episode has concluded that double dipping is just plain gross.” Not just gross. “They found that three to six double dips transferred about 10,000 bacteria from an eater’s mouth to the remaining dip sample.”
  • Football transmits bacteria much like STDs. Yes that is right. Tara Parker-Pope in a blog via the New York Times is reporting about a Salon.Com discussion of MRSA (methicillin resistant Staphylococcus aureus). Salon was weighing in on a recent study that focused on transmission of MRSA among gay men. Salon dug out an New England Journal of Medicine article about MRSA transmission among football players. And Salon says “When it comes to spreading the bacteria, it is not homosexuals we have to worry about….The medical researchers were not studying gays, they were studying the St. Louis Rams. That is correct: football players; in particular, linebackers.”

What kid would want to study bacterial evolution when they grow up?

OK – I am a bit scared by this, because it shows how little I have changed since I was young. And in my memory, I was not a total science geek for my whole life (you know – I focus on the fact that in high school, I played baseball and hockey and other sports pretty seriously, I guess my memory skips over that I was captain of the math team too).

But I was digging through some old papers and found this … a paper I wrote in ninth grade. We got to select a topic for the paper and mine … “Describe one step in the evolution of a bacterium.” The funny thing is — I do not remember this at all. I mean, I remember reading books by Gould that got me interested in evolution. But surely Gould did not write a lot about bacterial evolution. Where did I come up with this topic? I haven’t a clue. Anyway – here is the essay – errors, fluffy handwriting, and all.

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

Leslie Orgel – Still Speaking Wisely and Openly Even After Death

OK – my mind has been blown. Leslie Orgel, who just passed away recently, has a new Essay in PLoS Biology called “The Implausibility of Metabolic Cycles on the Prebiotic Earth.” Anyone interested in the origin of life should check this out.

He had me at the beginning … and as usual has very clear discussions of the steps needed for life to have originated:

If complex cycles analogous to metabolic cycles could have operated on the primitive Earth, before the appearance of enzymes or other informational polymers, many of the obstacles to the construction of a plausible scenario for the origin of life would disappear. If, for example, a complex system of nonenzymatic cycles could have made nucleotides available for RNA synthesis, many of the problems of prebiotic chemistry would become irrelevant. Perhaps a simpler polymer preceded RNA as the genetic material—for example, a polymer based on a glycerol-phosphate backbone [5] or a phosphoglyceric acid backbone. Could a nonenzymatic “metabolic cycle” have made such compounds available in sufficient purity to facilitate the appearance of a replicating informational polymer?

The paper then discusses details of various metabolic cycles and why the current evidence is not completely convincing in terms of the exact path that was taken in the origin of life. Note to ID supporters – this does not friggin‘ mean that he is saying life could not have originated from non living systems. He is simply pointing out that our understanding of it is incomplete. As, by the way, is our understanding of how blood works. But that does not stop us from thinking that blood does in fact, well, work.

Anyway, once you get over the fact that some ID supporters will misuse his work, the end is a great call for what needs to be done:

The prebiotic syntheses that have been investigated experimentally almost always lead to the formation of complex mixtures. Proposed polymer replication schemes are unlikely to succeed except with reasonably pure input monomers. No solution of the origin-of-life problem will be possible until the gap between the two kinds of chemistry is closed. Simplification of product mixtures through the self-organization of organic reaction sequences, whether cyclic or not, would help enormously, as would the discovery of very simple replicating polymers. However, solutions offered by supporters of geneticist or metabolist scenarios that are dependent on “if pigs could fly” hypothetical chemistry are unlikely to help

Yes, that is right, he got “if pigs could fly” into a paper. He was a great scientist. And it is nice for me to see one more paper of his. And this one, unlike pigs, can fly forever, because it is truly OA.

Syphilis origin solved?

A new paper in PLoS Neglected Tropical Diseases attempts to tackle a rather sensitive topic – the evolutionary origin of treponematoses (i.e., diseases caused by bacteria in the genus Treponema including yaws, pinta, and the one everyone wants to know about – syphilis). The paper, by Kristin Harper and others uses evolutionary reconstructions to try and determine if good old Christopher Columbus played a role in bringing syphilis to the New World.

There was an extensive article about this study in the New York Times on 1/15/08 (by John Noble Wilford). Overall the Times article is good (except Wilford gets the definition of phylogenetic analysis a bit wrong – saying it is the study of the evolutionary relationships between organisms when really it is the study of evolutionary relationships of anything… but hey that is OK).

I confess I am not sure if I am completely convinced by all of Harper et al’s arguments concerning the evolution of these bugs. My main concern is that the amount of variation they observe (in ~ 20 genes across these strains) is very very low. And thus the resolution of the phylogenetic trees is quite poor.

Because this is a PLoS paper, it is truly “Open Access” and I can include the Figure here in my blog as long as I cite the original source (see below). If you look at the tree you can see some #s on the branches in the tree. These are based on a statistical test called bootstrapping and the numbers indicate (roughly) how well the tree that is shown represents all of the polymorphisms in the data. The #s are percentages and alas the % support is not very high for many of the branches. So a better resolution of the question of the origin of these diseases will likely require, well, a better resolution on the tree. This in turn will likely require complete genome sequences and perhaps more strains samples. Nevertheless, given the results they have, their arguments seem sound … and this should stimulate people to gather more genomic data from these bugs.

Also see some other blogs on this

  • Neil Woodburn
  • John Dennehy (who mentions an article by Carl Zimmer in a non OA publication … find out which by going to his blog)

Here is Figure 3. It is from Harper KN, Ocampo PS, Steiner BM, George RW, Silverman MS, et al. (2008) On the Origin of the Treponematoses: A Phylogenetic Approach. PLoS Negl Trop Dis 2(1): e148. doi:10.1371/journal.pntd.0000148

Figure 3. This maximum likelihood tree is based on 20 polymorphic regions in the T. pallidum genome. Bootstrap support was estimated with 1,000 replicates in order to assess confidence at branching points and are shown within circles where values are high (>90%). Bootstrap support values for both maximum likelihood and maximum parsimony trees are shown, in that order.

Is that a sex organ on the cover of Nature?


OK — dipping into the gutter here a bit.  But everyone must check out the cover of Nature this week.  The issue is on the genetics of sex, and I’ll be damned if that phycomyces colony on the cover (the one in the back) does not look like some sort of male sexual organ.  

I do not know where to go with this.  It has to be on purpose right?  Is this what they refer to in the cover caption as a “pseudo-sexual” structure?
And I know I am probably not supposed to say this as an obsessed supporter of Open Access publishing but I dream of the day Nature becomes a fully OA journal.   I still think PLoS Biology is a better journal, but Nature definitely has some good stuff there.