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

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.

Whose genome should Roche/454 sequence to make up for selecting Watson’s?

In honor of one of my favorite places on the planet, Cold Spring Harbor Laboratory, I am trying to distract some of the negative attention that has come from James Watson’s latest choice of words. So I am calling on everyone in the community to come up with recommendations for whose genome Roche should sequence with the 454 technology to make up for the fact that they did Watson’s genome. And it would be good if the pick was someone that would make Watson a bit queasy.

Here are my top picks

  • Condoleezza Rice. An absurdly powerful, smart, black woman.
  • Francis Crick. Someone has to have some of his hair somewhere.
  • Rosalind Franklin. Not sure about the hair. But wouldn’t it be great if she was one of the reference genomes.
  • Francis Collins. Apparently no love lost between Francis and Jim.
  • Craig Venter. Sure his genome has been nearly completed. But why not do it again with another method.

Any other suggestions that would stick in Watson’s craw?

GME 2007 – Genomes, Medicine and the Environment

I am now at the “Genomes, Medicine and the Environment” conference in San Deigo. It looks to be quite good and diverse. Here is the schedule for Monday. I will try and post notes either as they happen or later tonight. First note — my undergrad. advisor, Colleen Cavanaugh is showing some cool pictures of deep sea organisms and their symbionts that chemosynthesize for them. She says “genomics is literally like opening a window into our science, because we cannot culture any of these symbionts.” And now she is talking about our paper on the symbionts of the giant clam, Calyptogena magnifica. It is really cool for me to see this — Colleen was the person who got me interested in microbes and symbioses and even though I only worked in her lab for 1.5 years, it changed my life and scientific career.

NOTE – I AM POSTING SOME NOTES IN THE COMMENTS ON THIS ENTRY.

Opening Remarks, J. Craig Venter, Ph.D., JCVI
Synthetic Biology
Colleen Cavanaugh, Ph.D., Harvard University – “Genomic Insights into Chemosynthetic Symbioses”
Nancy Moran, Ph.D., The University of Arizona – “Genomics of Symbiotic Bacterial Communities within Insects”
Hamilton Smith, M.D., J. Craig Venter Institute – “Toward a Minimal Cell”
BioEnergy
Steve Briggs, Ph.D., University of California, San Diego – ” Development and Application of Protein Profiling Methods”
Yuri Gorby, Ph.D., J. Craig Venter Institute – “Electromicrobiology: The Role of Bacterial Nanowires in Extracellular Electron Transfer”
Edward Bayer, Ph.D., Weizmann Institute of Science – “Bioengineering of Cellulosomes: Prospects for Conversion of Biomass to Bioenergy”

12:00-2:00 Lunch, Sunset Ballroom

Environmental Genomics
John Heidelberg, Ph.D., University of Southern California – “Genomic, Metagenomic and Functional Analyses of Cyanobacteria from Hot-Spring Microbial Mats”
Gene Tyson, Ph.D., Massachusetts Institute of Technology – “Metatranscriptomic Analysis of Microbial Communities in the North Pacific Subtropical Gyre”
Syed Hashsham, Ph.D., Michigan State University – “Understanding Microbial Community Succession in Response to Substrate Shock using Roche 454 GS FLX Sequencing System”
David Schwartz, M.D., National Heart, Lung & Blood Institute Toxicology Program – “Environmental Genomics and Human Health”
Human Metagenomics
Ren Bing, Ph.D., University of California, San Diego School of Medicine – ” Annotating the Human Genome – a ChIP-chip Approach”
Russell M. Gordley, B.A., Scripps Research Institute – ” Evolution of Programmable Zinc Finger-recombinases with Activity in Human Cells “

The human genome war from a fun perspective

So I was browsing around Amazon because I have a new Evolution Textbook that just came out. And when I searched for “genomics” and “evolution” up popped a “Listmania” list (which I had never heard of before) for Books about J. Craig Venter. And then I saw a new book by Craig – his autobiography “A life decoded: my genome: my life” coming out in October. And that’s when I discovered that the people who bought his book (even though it has not come out yet) also bought

So people apparently link Craig to atheism and Einstein. So I said to myself – what about other books by the genome-war folks? What else did people buy when they bought them? This is where the fun began.

Francis Collins: The Language of God.

So apparently, Francis has the religious readers on his side but nobody seems to link him to science in much of any way.

John Sulston’s a Common Thread

So it seems Sulston has gotten all the people interested in science history.

Michael Ashburner’s Won for All

So I guess Ashburner gets the people interested in the science itself.

I am sure there is more fun to be had here with these. And as my brother pointed out – the Amazon function here of listing what other people bought does not say it is representative in any way (that is, they are trying to sell books so perhaps they list the most popular other books not the ones most commonly linked to the book in question). But it is kind of voyeuristic and fun to see the types of books people are buying in association with these books.

Best genomics news article title …6 Billion Bits of Data About Me, Me, Me!

Gotta love the title of this article. It captures the essence of the new race to sequence ones own genome pretty well (with Jim Watson and Craig Venter leading the way). Clearly, this type of personal genomic medicine is coming whether we like it or not but, for those interested in getting ones own genome sequenced, here are some things to consider:

1. There will be many mistakes, at least with current methods. Get ready for lots of false positives and negatives relating to risk.

2. People will use it against you. Companies. Friends. Relatives. The government. This is not to discourage people from doing it (well, maybe a little bit). But given our current inability to keep anything important private in this country and our apparent inability to not snoop into people’s lives, this is going to be one overwhelming temptation for many people. Now is clearly the time to move forward with anti-discrimination laws.

3. Having your genome sequence will not automatically improve your health. It could even make it worse (e.g., see false positives above)

4. If you REALLY want to understand some of your biology from your genome, you are going to want to take a peak at the genomes of relatives. Good luck on all the family issues that will come up.

5. Just because Watson and Venter are releasing their genomes to the public does not mean you have to (for medicine it is VERY useful to have a genome associated with an individual … even many individuals, but there is no real need for names to be there)

6. The methods being used may not recover the haplotypes well (e.g., see Keith Robison’s blog).

ALSO check out some other articles on this topic

Let Colbert Decide: Francis Collins vs. Craig Venter

Well, I walked into a coleagues office and saw them watching Craig Venter on the Colbert Report. They asked me if that was what he was really like (I said no) and then they told me something I somehow missed. Francis Collins had also been on Colbert recently.

So – lets continue the public versus private fight right here on my blog.

The interview with Francis Collins is available here (http://www.comedycentral.com/motherload/?lnk=v&ml_video=79238).

The interview with Craig Venter is available here (http://www.comedycentral.com/motherload/?lnk=v&ml_video=82848)

I will refrain from commenting but I would like to solicit comments from others — pretend this was a debate. Who won?

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In response to Chris G’s comment I am posting pictures of Ned Flanders and Hunt Willard


Venter Global Ocean Voyage Press Conference

For those interested in metagenomics, microbial diversity and ocean microbiology, there will be a press conference tomorrow run by the Venter Institute relating to a series of papers (I am an author on some) coming out in PLoS Biology. The papers relate to Venter’s Global Ocean Voyage – sailing around the world collecting microbial samples. These were then used for environmental shotgun sequencing and the papers discuss various aspects of analzying the data.

Say what you want about metagenomics, and Craig and genomics, if you are a critic. But (1) read the papers, (2) give Venter some credit for publishing in an Open Access journals unlike many of the so called “public” genome effort folks who generally only pretend to support public/open access to anything.

Here is a link to view the live web cast of the PloS Biology GOS Expedition publication press conference. The press conference will be held tomorrow March 13 from 10-11 a.m. EST. After tomorrow an archive of the web cast will be hosted on the JCVI web site.

The papers are now live on the PLoS Biology Web Site.

The Global Ocean Sampling Collection can be found here.

My essay on Environmental Shotgun Sequencing can be found here.