Bay Area Biosystematists Meeting: w/ Quenton Wheeler - Feb 9

Announcement below:

Bay Area Biosystematists Meeting: Tuesday, 9 February, 2010

at UC Berkeley, 2063 Valley Life Sciences Bldg.

"Biodiversity Discovery"

Featuring Quentin Wheeler from Arizona State University
Plus contributions from additional panel discussants TBA

Quentin Wheeler is a well-known insect systematist interested in biodiversity discovery, phylogenetics, and species concepts. He is University Vice President and Dean of the College of Liberal Arts and Sciences at Arizona State University. He was also one of the founders of the International Institute for Species Exploration at ASU (http://species.asu.edu/index), producers of the great You Tube video "Planet Bob" (http://www.planetbob.asu.edu/index.html), which uses humor to focus attention on biodiversity and taxonomy (and won a 2008 Webby Award).

Schedule and venue:
5:30 - social gathering with beverages and informal pizza dinner:
cost ca. $10, to be collected at door, 2063 Valley Life Sciences Bldg.,
UC Berkeley campus.
7:00 - talk followed by discussion, in same room.

Reservations required for beverages and dinner (but not the talk). Please email reservations to your host, Brent Mishler by Sunday, Feb. 7th

For a map of campus and view of VLSB, use the link below.
http://www.berkeley.edu/map/maps/ABCD123.html

All are welcome, members or not. If you want to join the Biosystematists, a venerable yet exceptionally lively group that provides the only inter-institutional seminar/discussion forum addressing evolutionary topics in the Bay Area, sign up for the mailing list at: https://calmail.berkeley.edu/manage/list/listinfo/babs-l@lists.berkeley.edu

Bad omics word of the day: connectome

Well, I have decided that I need to look beyond just new omic words to snark about here (I have been giving a "Worst New Omics Word Award" every once in a while"). So I am now going to post, as often as I can, a little ditty about any bad omics word that is out there. Yesterday's winner was "phenogenomics" which I posted only to twitter.

Today's winner is "connectome" (see for example NIH Launches the Human Connectome Project to Unravel the Brain's Connections, July 15, 2009 News Release - National Institutes of Health (NIH)). I think it's first major use was here but not sure. It even has a wikipedia entry which says:

A connectome is a detailed map of the full set of neurons and synapses within the nervous system of an organism. The production and study of such a map is known as connectomics.

Now I am not the first to be a bit annoyed by this word (e.g., see the Neurochannels blog post "Review of Seung's talk at SFN":

Incidentally, 'connectomics' is a cheesy mouthful of a word. Some words just weren't meant to be biologized with the -omics suffix, and 'connect' is one of them. 'Genomics,' cool. 'Proteomics,' a little annoying and not very creative. 'Connectomics,' stop the bus I want to get off. At the very least let's reserve the -omics for molecular biology. Thank goodness Bialek didn't try to pull us into the world of 'infomics.

Hat tip to Karl Broman for pointing this one out in comments here.

As with posts about other omes and omics words, I am not saying anything really at all about the science behind the word here. Just the word.

Wanted:Feedback on Importance of Finishing (Microbial) Genomes

To all

I am writing because I am working on a project to evaluate the importance of finishing microbial genomes. I know there has been lots of talk about this out there on the web and in papers, etc but I think a fresh discussion is useful. To get people up to speed below is a summary of the issue as I see it.

1. Shotgun sequencing: Genome sequencing relies generally on the shotgun method at the beginning of a project where DNA fragments from an organism of interest are sequenced in a highly random manner.
2. Assembly: After shotgun sequencing, the genome is assembled as best as possible into larger pieces (called contigs) and ordered sets of contigs (called scaffolds). All of this put together can be called an "assembly"
3. Gaps: After the assembly phase, there are almost always gaps in the assembly. These generally come in two forms:
• sequencing gaps (where we know two contigs go together in some orientation but where we do not know the sequence of the DNA in between the contigs)
• physical gaps (where we have sets of scaffolds but do not know how the connect to each other).
4. Quality: After the assembly phase, different components of the assembly can have different "qualities" where from example, some sections are somewhat ambiguous and others are highly reliable
5. Finishing: Using any combination of laboratory, computational and other analyses one can both fill in gaps in the assembly and improve the quality of the assembly. This can generally be called "finishing"
6. Quality of final product: Depending on the end quality of the assembly we could assign it to one of a few categories of "completeness" as outlined in a paper by Patrick Chain et al. In essence, you can consider the post to be a follow up to their paper and their work.
   

We plan to try to measure what one gains by the finishing steps. We need to know this because we would like to make intelligent decisions about how to allocate resources. If one gains a lot from finishing then it would make sense to allocate significant resources to it. I note, I and some colleagues wrote a paper about this issue "The value of complete microbial genome sequencing (You get what you pay for)" that was published in 2002. This is without a doubt not the only discussion of the topic but I just wanted to point out I have been involved in this debate before. Despite that, I think we simply do not know right now what the benefits might be in the new sequencing landscape.

------------------------------------------

So the question I am asking here is:

What do people think are the potential benefits that could come from finishing?

------------------------------------------

Here are some possible answers to get the discussion going:

1. Gene discovery (e.g., there may be interesting/important genes in missing/low quality data)
2. Esthetics of completeness (as in, it just feels better to have a finished genome)
3. Improved analysis of genome organization (in particular from having contigs oriented correctly)

Also - I note there has been some discussion of this for animals, plants etc (e.g., see recent paper by Eric Green and others on vertebrates) Many of the issues are similar but they are different enough that I think a microbe focused discussion is useful.

Other links of interest:

• Discussion on Friendfeed to question from Michael Barton
• LANL finishing in the future meeting
• Scivee talks from 2009 LANL meeting

Blakesley, R., Hansen, N., Gupta, J., McDowell, J., Maskeri, B., Barnabas, B., Brooks, S., Coleman, H., Haghighi, P., Ho, S., Schandler, K., Stantripop, S., Vogt, J., Thomas, P., Comparative Sequencing Program, N., Bouffard, G., & Green, E. (2010). Effort required to finish shotgun-generated genome sequences differs significantly among vertebrates BMC Genomics, 11 (1) DOI: 10.1186/1471-2164-11-21

Fraser, C., Eisen, J., Nelson, K., Paulsen, I., & Salzberg, S. (2002). The Value of Complete Microbial Genome Sequencing (You Get What You Pay For) Journal of Bacteriology, 184 (23), 6403-6405 DOI: 10.1128/JB.184.23.6403-6405.2002

Chain, P., & et al. (2009). Genome Project Standards in a New Era of Sequencing Science, 326 (5950), 236-237 DOI: 10.1126/science.1180614

Friendfeed discussion of this post:

Cool paper, & winner of "worst new omics word award": Predatosome

And the bad new omics words keep streaming in. Today's winner of the "Worst New Omics Word Award" is going to Carey Lambert, Chien-Yi Chang, Michael J. Capeness and R. Elizabeth Sockett from Nottingham for their use/ invention of "Predatosome". They use this term in the title of their new PLoS One paper: The First Bite— Profiling the Predatosome in the Bacterial Pathogen Bdellovibrio. Here is the very long sentence where the define it:

The gene products required for the initial invasive predatory processes have not been extensively studied but the genome sequencing of B. bacteriovorus HD100 [1] revealed a genome of 3.85Mb, including a core genome similar to that of non-predatory bacteria and some 40% of the genome comprising a potential predicted “predatosome” of genes, encoding both hydrolytic products that may be employed in prey degradation, and genes that may be required specifically for host predation and thus are not conserved across the Proteobacteria.

The paper is actually quite interesting. They use genomic approaches to characterize a fascinating organism - the bacterial species Bdellovibrio bacteriovorus. This bug is a predatory organism - eating other bacteria. Since it eats them from the inside out, some, including these authors, refer to this organism as a pathogen of other bacteria and their is some discussion here and elsewhere for its potential to serve as a "living antibiotic" in much the same way people are trying to use bacterial viruses (a.k.a. phage).

The paper overall is quite nice on first read. They used microarray studies to characterize gene expression patterns in different phases of the life cycle (see Figure above for the life cycle outline). They backed up this work by quantitative PCR studies and regular RT PCR. And based upon their analysis they found some genes that are "Up-Regulated in Predatory, but Not HI" phase (HI stands for host-independent). And here is where they really tell us what they mean by predatosome:

This category of 240 genes are very interesting as they potentially exclude those genes simply involved with release from attack-phase into growth, namely they should be part of the “predatosome” of predatorily specific genes.

It seems to me this terminology is completely unnecessary. All they need to do is say they are studying the genes related to the predatory phase. To assign these genes to the "predatosome" is a bit much. They continue in the paper to report some really interesting stuff. For example, they also examine another predatory bacterial species, and look at whether there are genes conserved in the process between species. They made some really nice figures by the way about the different phases of hte life cycle in this organism and which genes are expressed:

Anyway - the science in the paper is nice. However, the invention of yet another omics word is a bit much. And thus Lambert et al. are winners of the highly coveted "Worst New Omics Word Award" for their invention of "predatosome". Details on the paper are below - and that is where the figures come from too. (Hat tip to Bora for letting me know about the paper, and the word).

Lambert, C., Chang, C., Capeness, M., & Sockett, R. (2010). The First Bite— Profiling the Predatosome in the Bacterial Pathogen Bdellovibrio PLoS ONE, 5 (1) DOI: 10.1371/journal.pone.0008599

Friendfeed comments below:

ISI - late to index #PLoS One but now marketing that they do so

Well, just a mini post here. In case you did not know - PLoS One is now being indexed by ISI (see their announcement: PLoS ONE and see the PLOS blog post here
and see Erik Svensson's blog post for an interesting take) and will get an impact factor and be in their Citation Index and all such things. Now mind you, I think "Impact Factor" is a silly thing overall in that we should evaluate papers not journals per se.

So why am I writing this - because I find it pretty funny that despite being slow to recognize PLoS One ISI is now promoting the fact that they are indexing PLoS One on their home page. See the screen capture above.

GlaxoSmithKline opening up malaria data a wee bit, but more needed

Robert Langreth in an article at Forbes.Com on January 20 (GlaxoSmithkline's Malaria Plan: Limit Profits, Open Labs) reports that Glaxo Smith Kline is becoming a bit more open with their data on malaria drug/vaccine development.  Apparently, they plan to open up their labs and some of their data to non profit collaborators such as Emory University.  Sounds like this could be a good first step.  But if they really want to advance malaria vaccine research, perhaps they should release their data to everyone? I get that they want/need to make a profit, but if they want to try and get credit for being open, I think they really should jump into the deep end and do something radical.  Just sharing bits and pieces of data with a few labs is not a particularly stunning move.

More from Yolo Basin

Here are some pictures from a recent trip to Yolo Basin

Fun at the #UCDavis Raptor Center

Some pics from a family visit to the UC Davis Raptor Center open house

Enough w/ the good: here are the top10 problems w/ the #scio10 meeting

Well, the blogosphere has been all atwitter with glowing feedback about the Science Online 2010 meeting (see Bora's collection here). I even wrote some nice things (see "Top 11 things I learned at Science Online (#scio10) " and "And the real mission of #scio10 is fulfilled: kids play with educational freebies". Well I for one have had enough. Thus, even though this meeting was the most exciting meeting I have been to since Science Foo camp, I think we all need to put on our snarky hats and point out some general flaws with the whole #scio10 enterprise. And here are but a sampling of some of the unpleasant things about the meeting.

1. There were many people at the meeting who, like some sort of celebrity, are known either by just one word or by their first name. Bora. Dr. Kiki. The Skloot. Dr. Isis., etc. (though I note, there was an actual Hollywood actress at the meeting). There were multiple people who went by "Goddess" in one way or another. There was a GarbageGirl a Spiderman, a Pharmboy and a DrugMonkey and yes, even a Pervwank. There was even someone who goes by the kind of shoes he wears and another by the color of her lab coat. And not only were there nerds galore, there were people who wanted to be called a nerd or just let it be known they were "curious". There was even extensive discussion of scientists giving someone else a nickname to try to hide their identity. And so on. I mean, come on. We all know that the only way to keep track of scientists and people contributing to science is by formal full names right?
   
2. There were not an even number of males and females. Sure it was just a difference of one (133 men, 134 women). But come on that is so biased.
   
3. There were some sessions where some of the people attending the session were not live blogging or tweeting. I know, how could they? Well, it is possible their batteries ran out on their phones, but I mean, really, this is a meeting called "Science Online 2010". If you are going to go to such a meeting you must bring the right tools.
4. Someone bumped into the light switch during the keynote talk and shed light on it right when it was getting juicy. The atmosphere was crushed.
5. There have not yet been any books published about the meeting. It's true, in the sense that I did an Amazon search and did not find any (note to fact checkers - check that please).
6. Though they indeed did provide free coffee and espresso drinks - but the bar at the hotel was unable to make mojitos. Bad hotel. Bad hotel.
7. The hotel had sleep number beds but did not provide any Youtube videos for how to use them. How are we expected to figure out what to do?
8. Nobody sequenced any genomes at the meeting. Yuck.
9. Some people took notes on paper. How on earth are they going to tweet while writing stuff down?
   
10. A new flu strain was created by all the recombining ideas and discussions of the sexual behaviors of ducks, cuttlefish and other organisms at the meeting. It is now known as scion flu, or H10N10. At least something form the meeting went viral.
11. (Yes, this one goes to 11). The even allowed people under 18 to the meeting. Creepy and unacceptable.

Friendfeed discussion here:



And thanks to many for comments / retweets on twitter including:

Confronting Intelligent Design arguments directly in the scientific literature

A representative from Wiley publishing sent me a link to an interesting new paper. Entitled "Using Protistan Examples to Dispel the Myths of Intelligent Design" by Mark Farmer, from the University of Georgia and Andrea Habura, from the University at Albany, New York. It is from the Journal of Eukaryotic Microbiology and is based upon a presentation they gave at a workshop at a conference.

Basically, the article is a detailed discussion of how examples relating to microbial eukaryotes (I hate the term protist ...) that are used by Intelligent Design advocates are, well, BS. And the article discusses the evidence that refutes the ID arguments.

One thing they discuss is the issue of the Cambrian Explosion. ID supporters, such as Stephen Meyer have made many arguments about they feel the diversification in the Cambrian is not explainable through evolutionary processes. Farmer and Habura refute this by pointing out that the diversity seen in microbial eukaryotes at the time of the Cambrian was immense and that what came out of the "explosion" was actually not that spectacular relative to what already existed in the microbial eukaryotes:

The extant diversity of the protists should therefore be seen as the "background radiation" of the eukaryotic Big Bang, with the Cambrian radiation of the metazoa being a subsequent event within a specific group.

They go on to discuss examples involving speciation, the fossil record, evolution of drug resistance in Plasmodium, and a few other things. In each case they discuss a claim by ID supporters and then discuss evidence for why this claim is not valid. Overall the paper is worth reading if you are involved in any discussions with ID supporters.


I note that when I finished the above writing, I went to look at Pubmed to find other examples of people taking on ID arguments in the literature with a focus on issues in microbes. Here are two other recent examples:

• Introduction: Protistan Biology, Horizontal Gene Transfer, and Common Descent Uncover Faulty Logic in Intelligent Design.
• Bacterial flagella and Type III secretion: case studies in the evolution of complexity.

Some discussion of this has now popped up on the web:

• Protozoans Against Intelligent Design
• Genome Web "This might count as preaching to the choir"

FARMER, M., & HABURA, A. (2010). Using Protistan Examples to Dispel the Myths of Intelligent Design Journal of Eukaryotic Microbiology, 57 (1), 3-10 DOI: 10.1111/j.1550-7408.2009.00460.x

And the real mission of #scio10 is fulfilled: kids play with educational freebies

Top 11 things I learned at Science Online 2010 (#scio10)

Well, Science Online 2010 is over.  If you want to know the details of the meeting see some of these places: Twitterkeeper collection of tweets, Blog and Media Coverage, and lots of other places online.

I am sitting in my hotel room, kind of wishing I had gotten an earlier flight back but also hoping that a friend of mine from NC State will have some free time tomorrow.  Anyway- I will post more about the meeting later but wanted to put out a few things before I forget them here.  Here is my List of the Top 11 things I learned or relearned at Science Online 2010.

1. Contrary to what some many claim, science journalism is not dead and I was really impressed by how much science reporters really care about the quality of their work
2. Systems like twitter, facebook, blogs, podcasts, slides, games are neither good nor bad but ALL can be used in good or bad ways in regard to communicating science (I kind of knew this already but have had it confirmed)
3. No matter how good sessions are at a meeting, the best stuff happens outside of sessions in the hall, bar, etc
4. Adding a bit of humor to a meeting or presentation is fantastic; and not done enough; in general, 'Science' needs more humor 
5. Working hard to promote and market something you do is fine and in fact, very useful; but marketing something of little or no relevance (especially to a captive audience) - not so good
6. People with passion about their work (of which there were an amazing collection at the meeting) can get people interested in ANYTHING; people without passion, can suck the life out of the coolest thing ever
7. Though it is true that there are continuing issues with the existence of "anti-science" groups and movements, people still seem to inherently love science; related to this, a key task for science supporters is to focus attention on teaching critical thinking
8. Openness in science continues to spread, in publishing, education, outreach, data, etc. 
9. Many of the "systems" connected to carrying out science still need work, from recruiting minorities, to tenure review, to peer review, to evaluating quality and contributions, etc. 
10. Related to #9 - we need to avoid portraying scientists as having some sort of super level of virtue (e.g., scientists lie, forget, cheat, smell, can be total schmucks, screw up, etc).
11. The spread of citizen science projects is something I did not expect, but a very interesting and exciting aspect of science now
12. (Bonus) Meeting people you only knew from their online presence is much more fascinating than I expected; meeting so many at once overwhelming; liking both their online and real personas - priceless

Anyone out there want to add others?

And see the FriendFeed comments on this post below:

Wanted - input on topics for "open access" publishing discussion at #scio10

To all

I am posting this because I will be chairing a session this up coming weekend at Science Online 2010 on "Open Access" publishing.

And I would love input from everyone/anyone out there on what might be worth discussion at this session.  Possible topics include

• why open and free are not the same thing
• open access mandates
• financial aspects of OA
• educational uses of OA literature 
• things that are slowing the inevitable spread of OA publishing

I am perhaps most interested these days in the last two on that list.  For example - it seems that OA publishing would spread even faster if we did not have some very conservative styles of tenure, promotion, hiring and grant review processes.

If anyone has some pressing topics that you think are worth bringing up in a discussion of OA publishing, please post them here.

Gmail account deletion phishing attempt ...

Just got this in my inbox - have never received any phishing directed at my gmail account before - maybe this is a follow up to google's issues with China?

Gmail Alert
reply-to
infotechcrewacess@gmail.com

to

date
Wed, Jan 13, 2010 at 12:34 PM
subject
Verify Your Gmail


hide details 12:34 PM (5 minutes ago)

We are shutting down some email accounts and your account was automatically chosen to be deleted. If you are still interested in using our email service please fill in the space below for verification purpose by clicking the reply button and fill the form below. Learn more

Account: Password: Birth date: Country:

Warning!!! Account owner that refuses to update his or her account within Seven days of receiving this warning will lose his or her account permanently.Thank you for using Gmail !

The Gmail Team
G MAI L BETA

Ooh - my first Epernicus spam

Just got this via Epernicus -  is it a sign that Epernicus is attracted more attention? (For those who do not know, Epernicus is a professional networking system for scientists)

Nice To Meet You,
How are you today ?,My name is (deleted) Hight,fair in completion ,i saw your profile today on (www.epernicus.com) and after going true it i was moved with the quality i found in
your profile,which makes me to became interested in knowing you the more. but i will like you to no that distance ,age or color dose not matter but what maters is love and understanding and being honest to each other. i will like you contact me true my direct mailing address so that i will give you my picture and tell you more about me. (email deleted)i have SOMETHING VERY IMPORTANT to tell you.Good to hear from you,
(email deleted)
Yours dream love. And Happy New Year,
(deleted)

UC Pres. Yudof (@mark_yudof) statement regarding California budget

Just got this in an email from UC President Mark Yudof

Nice "Tree of life" video from Peabody Museum

I think I have written about this before but here goes again.  There is a nice "Tree of Life" video from the Peabody Museum that is now on Youtube and also their web site that is definitely worth a look for people interested in phylogenetics and the tree of life. It includes Michael Donoghue, Scott Edwards, David Hillis, Tandy Warnow and Charles Davis.

Can you apply the laws of science to the science of laws? try this CCST fellowship

Just got this announcement for this important Fellowship program.  A student who got her PhD in my lab just started in this program for this years group (see the SJ Mercury News Story about this program here). Love the flyer by the way "Can you apply the laws of science to the science of laws?". Email announcement is below:

"The California Council on Science and Technology (CCST) is pleased to announce that applications are now being accepted for the 2010-2011 California Science and Technology Policy Fellowships based in Sacramento.

The S&T Policy Fellowship, a unique one-year professional development opportunity, provides the selected fellows with hands-on experience working with the California Legislature to incorporate science and technology into public policy. Eligible applicants will be PhD-level (or equivalent) scientists and engineers who have a sincere interest in California current events, the state legislative process, and a strong desire to learn how policy decisions are made.

Please forward this announcement to any individuals or group listservs that may be interested in this exciting opportunity. Deadline for submission of applications is February 12, 2010 at 5:00 p.m. PST. More information is available at http://www.fellows.ccst.us."

#PLoSOne paper keywords revealing: (#Penis #Microbiome #Circumcision #HIV); press release misleading

UPDATE - READ COMMENTS - LEAD AUTHOR HAS GOTTEN PRESS RELEASE CHANGED

A new paper just showed up on PLoS One and it has some serious potential to be important The paper (PLoS ONE: The Effects of Circumcision on the Penis Microbiome) reports on analyses that show differences in the microbiota (which they call the microbiome - basically what bacterial species were present) in men before and after circumcision. And they found some significant differences. It is a nice study of a relatively poorly examined subject - the bacteria found on the penis w/ and w/o circumcision. This is a particularly important topic in light of other studies that have shown that circumcision may provide some protection against HIV infection.

In summary here is what they did - take samples from men before and after circumcision. Isolate DNA. Run PCR amplification reactions to amplify variable regions of rRNA genes from these samples. Then conduct 454 sequencing of these amplified products. And then analyze the sequences to look at the types and #s of different kinds of bacteria.

What they found is basically summarized in their last paragraph

"This study is the first molecular assessment of the bacterial diversity in the male genital mucosa. The observed decrease in anaerobic bacteria after circumcision may be related to the elimination of anoxic microenvironments under the foreskin. Detection of these anaerobic genera in other human infectious and inflammatory pathologies suggests that they may mediate genital mucosal inflammation or co-infections in the uncircumcised state. Hence, the decrease in these anaerobic bacteria after circumcision may complement the loss of the foreskin inner mucosa to reduce the number of activated Langerhans cells near the genital mucosal surface and possibly the risk of HIV acquisition in circumcised men."

And this all sounds interesting and the work seems solid. I note that some friends / colleagues of mine were involved in this including Jacques Ravel who used to be at TIGR and now is at U MD and Paul Kiem who is associated with TGen in Arizona. For anyone interested in HIV, the human microbiome, circumcision, etc, it is probably worth looking at.

However, the press release I just saw from TGen really ticked me off. The title alone did me in "Study suggests why circumcised men are less likely to become infected with HIV". Sure the study did suggest a possible explanation for why circumcised men are less likely to get HIV infections - the paper was justifiably VERY cautious about this inference. They basically state that there are some correlations worth following up.

The press release goes on to say "The study ... could lead to new non-surgical HIV preventative strategies for the estimated 70 percent of men worldwide (more than 2 billion) who, because of religious or cultural beliefs, or logistic or financial barriers, are not likely to become circumcised." Well sure, I guess you could say that. I think they are iplying you could change the microbiome somehow and therefore protect from HIV but that implies (1) that there really is a causal relationship between the microbial differences in HIV protection and (2) that one could change the microbiome easily, which is a big big stretch given how little we know right now.

Anyway - the science seems fine and not over-reaching. But the press release is annoying and misleading. Shocking I know. But this one got to me.

UPDATE - SEE COMMENTS HERE AND IN FRIENDFEED. LEAD AUTHOR GOT PRESS RELEASE CHANGED.



Price, L., Liu, C., Johnson, K., Aziz, M., Lau, M., Bowers, J., Ravel, J., Keim, P., Serwadda, D., Wawer, M., & Gray, R. (2010). The Effects of Circumcision on the Penis Microbiome PLoS ONE, 5 (1) DOI: 10.1371/journal.pone.0008422

Story behind the science: #PLoS Biology paper on cichlid vision evolution

I am continuing on a new theme here in trying to get author feedback on recent PLOS publications.  Today I write about a recent paper on PLoS Biology "The Eyes Have It: Regulatory and Structural Changes Both Underlie Cichlid Visual Pigment Diversity" by Christopher Hofmann, Kelly O'Quin, N. Justin Marshall, Thomas Cronin, Ole Seehausen and Karen L. Carleton

This paper discusses "how changes in gene regulation and coding sequence contribute to sensory diversification in two replicate radiations of cichlid fishes." A good overview of the paper is in an accompanying article "Visual Tuning May Boost African Cichlid Diversity" by Robin Meadows:

"African cichlid fish form new species faster than any other vertebrates, with hundreds of species evolving within the last 2 million years in Lake Malawi and within the last 120,000 years in Lake Victoria. This rapid speciation makes cichlids good models for elucidating the genetic mechanisms behind biodiversity. Vision may play a key role in cichlid evolution, adapting them to forage for new foods or colonize new habitats. Vertebrate retinas have two groups of light-sensitive proteins called opsins: those in rod photoreceptors, which are sensitive to dim light, and those in cone photoreceptors, which are sensitive to color. Changes in the visual system could be due to differences either in the expression of opsin genes or in their DNA sequences. A Research Article in this issue of PLoS Biology by Christopher Hofmann and colleagues suggests that both mechanisms underlie changes in visual sensitivity in cichlids."

For more on the science, see her summary and see the article itself. Additional information can be found in the press release from U. MD

But what I wanted to cover here was some of the story behind the science.  So I emailed the authors some questions which they were kind enough to answer and I post the details here. There are some really interesting tidbits in these answers in my opinion, including how they dealt with merging two papers into one, and how difficult (but fun) it is to do this field work in Lake Malawi.

Barcoding, taxonomy and citizen CSI

I just love the continued coverage of the story of the students from Trinity School in New York (a high school) who do investigative DNA barcoding projects. (There is a good new story about this on the LA Times blogs at:Think that sheep's mik cheese comes from a sheep? DNA doesn't lie | Booster Shots | Los Angeles Times)

In the most recent example, two students, Brenda Tan and Matt Cost, did some home barcoding in collaboration with people from the AMNH and Rockefeller University.

Among their findings:

• "an invasive species of insect in a box of grapefruit from Texas"
• "what could be a new species or subspecies of New York cockroach"
• multiple mislabelled food products including (quoted from the press release, I note)
• An expensive specialty “sheep’s milk” cheese made in fact from cow’s milk;
• “Venison” dog treats made of beef;
• “Sturgeon caviar” that was really Mississippi paddlefish;
• A delicacy called “dried shark,” which proved to be freshwater Nile perch from Africa;
• A label of “frozen yellow catfish” on walking catfish, an invasive species;
• “Dried olidus” (smelt) that proved to be Japanese anchovy, an unrelated fish;
• “Caribbean red snapper” that turned out to be Malabar blood snapper, a fish from Southeast Asia.

And what I find most interesting, is this built upon work of other students from Trinity Kate Stoeckle and Louisa Strauss who had done a restaurant based barcoding study last year. 

This type of work is cool in so many ways.  It gets students into science.  It is an applied us of taxonomy (though I note, barcoding is not without controversy in the taxonomy community). It is a useful form of citizen science -- and may eventually provide a way to keep dishonest sellers on their toes ... Kudos to all involved in this 

More on this story can be found at

• Teens turn into DNA detectives
• With DNA Testing, Students Learn What's What in Their Neighborhood
• Doing their 'pest'
• New York High Schoolers May Have Discovered New Cockroach Species

Evolutionary classification applied to soups & meals

Written by Saul Jacobson - I think to mock me but you never know with him:

Molecular comparisons show that soup on this planet divides into three primary groupings, commonly known as the stews, the broths, and the chowders. The three are very dissimilar, the differences that separate them being of a more profound nature than the differences that separate typical meals, such as steaks and salads. Unfortunately, neither of the conventionally accepted views of the natural relationships among meals -i.e., the five-kingdom taxonomy or the appetizer/dinner dichotomy--reflects this primary tripartite division of the eating world. To remedy this situation we propose that a formal system of meals be established in which, above the level of eating, there exists a new taxon called a "course." Meals on this planet would then be seen as comprising three courses, the appetizer, the main course, and the dessert, each containing two or more plates

Good last minute place to donate $$ - Explorit Science Center in Davis

Just got an email saying that the Explorit Children's Science Center in Davis is hurting for funding.  See below - please consider donating to this worthy cause ...

Cash-strapped Explorit appeals to community for support

For 28 years, Explorit Science Center has been a gem of the Davis community and an educational boon to the Sacramento region, providing hands-on science opportunities for thousands of families and schools.

Now, the center is confronting a challenge that science can't address. Financial struggles are threatening the existence of Explorit's main site at 2801 Second St., which was purchased in 2006.
In response, the center is appealing to the community for support.

 "We know this is a philanthropic community, and one that strongly believes in furthering the education of our children," says Lou Ziskind, executive director. "We need help to keep the Explorit mission alive."

Ziskind attributed the financial difficulties to the down-turned economy and unfortunate timing in the center's purchase of the Second Street site.

"Government funding for education is down, corporate donations and grants are scarce, and understandably, individuals just cannot contribute like they could a couple years back," he said. "Income from program fees, also a key revenue source, have shrunk as well."

"The bigger concern, however, is that in 2006, when the economy seemed sound and real estate values were rising, we obtained bridge financing to complete the purchase of our building," Ziskind said. "With a drop-off in income, we are struggling with the repayment terms of our $1.6 million loan. Without additional financial support, our ability to run our Second Street facility will be in jeopardy."

Ironically, the museum is thriving in many ways. It is breaking attendance records -- 2,391 visitors in November was a 40 percent increase over November 2008  -- and visitor evaluations have been very positive.

"We've finished our phased-in opening of the museum so there is more fun stuff to do than ever," Ziskind said. "We've also been getting great media attention with new attractions like our streambed table and new promotions like "Toddler Tuesday."

Explorit's Board of Directors and staff believe that the need for the center's informal science education programs is greater than ever.

"In Davis, we're fortunate to have a school budget that allows for science education in elementary classrooms," said Betsy Elzufon, an Explorit trustee and mother of two. "Sadly, in many other towns, the students' only hands-on science experiences are those provided by Explorit's traveling programs. For those schools, it is truly a blessing to have us help fill the void and educate these students about the importance science lends to our daily lives."

To keep the Explorit vans rolling and the museum open, Explorit offers a package of ways to lend support, says Peter Willson, the development director. The organization is a nonprofit 501 (c)(3) organization; donations are tax-deductible.

"We have a 'Donate' button on our website, of course," he said, referring towww.explorit.org. "That's the easiest and fastest. We also gladly take cash or check donations at the museum during visiting hours or through the mail (to Explorit at P.O. Box 1288, Davis CA 95617). Then our website has lots of other information about ways to help, including a new car-donation program."

He and board members are hopeful that the center will weather the recession.

"This place has been a great part of the community for over a quarter-century and has meant so much to the families in Davis and the greater Sacramento region," Elzufon said. "It would be a sad day if we were not able to continue offering our many valuable programs to the many families, schools, and educators who depend on us."

For more information about Explorit, please contact Peter Willson at (530) 757-4530 ext. 112 or e-mail him at PeterW@explorit.org. 

  

Top days of the week for 2009 stunner: Tuesday #1, Friday last place

Well, the results of our detailed survey are in.  With the help of people from all around the world, we have classified and rated days of the week for 2009 based upon a large number of criteria.  A really large number of criteria.  And the rankings are:

1. Tuesday.  In a big surprise, Tuesday won out over the other days.  Our analysis indicates that this was due more to dislike of other days rather than the popularity of Tuesday itself.  In particular, the problems this year with Friday not only took down Friday, but also Thursday (see below).  In addition, Tuesday allied itself early on with the always popular Saturday when Saturday broke with Friday over the furlough issue. And Tuesday always scores well with the Monday haters, because when it comes, that is proof they made it through their nemesis.  Congratulations Tuesday.
2. Saturday. Riding on Tuesday's coattails and it's own strength as the first day of the weekend, Saturday moved up from last years poor performance to snag a second place. Clearly the break with Friday paid off as apparently did Saturday's decision to not run any negative campaigns against Sunday as it did last year with it's "Sunday, the day before Monday" campaign. 
3. Sunday. Despite a general impression of being dull and boring, Sunday this year snagged it's traditional third slot because people viewed it as a safe bet and it still won out the traditional "weekend" voters. Also - Sunday negated the negative ads from last year by hiring a skilled rapid response team that posted humorous YouTube videos mocking any negative ads that came out.
4. Wednesday. Rolling in at fourth position is Wednesday.  Never popular.  Never disliked.  But always right in the middle. Normally in competition with Tuesday and Thursday for the fourth spot, Wednesday beat out Thursday by a wide wide margin this year, most likely due to the Friday issue but simply could not compete with Tuesday's excellent campaign.
5. Thursday. What a downturn for Thursday. Last year third.  This year the bottom of the middle in a deep fifth place.  Sadly, this was something out of Thursday's control as the enormous unpopularity of Friday simply killed Thursday's campaigning.  Many see this a a fair turn of events, as Thursday previously has ridden its position near the end of the work week to popularity despite not really doing much of anything special.
6. Monday. The big shocker this year.  Monday moved up from it's traditional seventh spot to get a #6. Clearly, this was in a large part due to some issues with Friday but also Monday ran a very smooth campaign focusing on it's strengths (e.g., many Holidays) and acknowledging rather than ignoring its weaknesses. Monday has publicly stated that it is aiming for #5 next year, at whatever the cost.  Our prediction - not going to happen.
7. Friday. From first to last, in one year.  Friday won last year and in many previous years where it usually duked it out with Saturday for top spot.  But this year Friday was killed by furloughs.  Not only did the people who were furloughed on Friday vote against it, but so did all the people who had to wait in line at DMV's and other government offices.  In addition, Saturday and Thursday teamed up for a brilliant ad campaign pointing out that just about everyone knew someone who was furloughed, and they suggested early in the year that it would be immoral to even "feel" happy on Friday.  This campaign killed Friday's chances early on. And with the financial issues continuing it looks like Friday may have trouble next year too.

More coverage of the GEBA "Phylogeny Driven Genomic Encyclopedia"

Just a quick note here to post some links to additional stories about my new paper on "A phylogeny driven genomic encyclopedia of bacteria and archaea" which was published last week in Nature (with a Creative Commons license - which is rare in Nature but is what they use for genome sequencing papers).

Carl Zimmer has an article today in the New York Times "Scientists Start a Genomic Catalog of Earth’s Abundant Microbes"  about the paper and the project.  In the article he interviews me and Hans-Peter Klenk, who was a co-author and led the culturing part of the project.  A few things to note about this:

• It is rare to have archaea mentioned in the New York Times.
• There is a tree that goes along with the article which is a modified version of the tree we had in our paper.  I think theirs is very nice. Kudos to their artist
• There is a quote by Norm Pace generally supportive of the project 
• The article mentions the JGI Adopt a Microbe program and even has a shout out to Malcolm Campbell at Davidson College and his recent PLoS One paper where they discuss results from a project where they took one of the genomes from our project and used it as part of a course on genome annotation/analysis. 

For some of the story behind the paper see my recent blog post "Story Behind the Nature Paper on 'A phylogeny driven genomic encyclopedia of bacteria & archaea' #genomics #evolution"

Other discussions worth checking out

• John Timmer's article for Ars Technica on "Presenting a genomic encyclopedia of bacteria (and archaea)" 
• The Department of Energy is featuring the project as part of their "National Impact" Series" Scientists Launch the Genomic Encyclopedia of Bacteria and Archaea
• NYTimes Science Times discussion from Charlie Petit at the Knight Science Journalism tracker

Also see

• Archaea Make the Big Time from Genome Technology
• Woodland Daily Democrat (local paper): Encyclopedia of microbe genomes released
• Cory Golden at The Davis Enterprise wrote a nice story "Researchers urge new take on microbes" - not sure how long this stays online or how people access it though
• Microbe World has a bit on it
• Leonardo Martin has a really nice round up here
• The ScientificBlogging staff have written a bit about it here
• R&D mag Sr Editor Paul Livingstone has an interesting take on the story: Obsessive compulsive taxonomy
• Green Car Congress with mostly material from the press releases here. 
• MyCor Web has a nice discussion of the paper 

Wu, D., Hugenholtz, P., Mavromatis, K., Pukall, R., Dalin, E., Ivanova, N., Kunin, V., Goodwin, L., Wu, M., Tindall, B., Hooper, S., Pati, A., Lykidis, A., Spring, S., Anderson, I., D’haeseleer, P., Zemla, A., Singer, M., Lapidus, A., Nolan, M., Copeland, A., Han, C., Chen, F., Cheng, J., Lucas, S., Kerfeld, C., Lang, E., Gronow, S., Chain, P., Bruce, D., Rubin, E., Kyrpides, N., Klenk, H., & Eisen, J. (2009). A phylogeny-driven genomic encyclopaedia of Bacteria and Archaea Nature, 462 (7276), 1056-1060 DOI: 10.1038/nature08656

Bakke, P., Carney, N., DeLoache, W., Gearing, M., Ingvorsen, K., Lotz, M., McNair, J., Penumetcha, P., Simpson, S., Voss, L., Win, M., Heyer, L., & Campbell, A. (2009). Evaluation of Three Automated Genome Annotations for Halorhabdus utahensis PLoS ONE, 4 (7) DOI: 10.1371/journal.pone.0006291

Story Behind the Nature Paper on 'A phylogeny driven genomic encyclopedia of bacteria & archaea' #genomics #evolution

Today is a fun day for me. A paper on which I am the senior author is being published in Nature (yes, the Academic Editor in Chief of PLoS Biology is publishing a paper in Nature, more on that below ..). This paper, entitled, "A phylogeny driven genomic encyclopedia of bacteria and archaea" represents a culmination of years of work by many people from multiple institutions. Today in this blog I am going to do my best to tell the story behind the paper - about the people and the process and a little bit about the science.

First, a brief bit about the science in the paper. In this paper, we (mostly people at the Joint Genome Institute, where I have an Adjunct Appointment -- but also people in my lab at UC Davis and at the DSMZ culture collection) did a relatively simple thing - we started with the rRNA tree of life as a guide. Then we identified branches in the bacterial and archaeal portions of this tree where there were no genome sequences available (or in progress) (this was done mostly by Phil Hugenholtz, Dongying Wu and Nikos Kyrpides) Next we searched for representatives of these "unsequenced" branches in the DSMZ culture collection (a collection of bacteria and archaea that can be grown in the lab). And we identified in total some 200 of these. And then the DSMZ (under the direction of Hans-Peter Klenk) grew these organisms and sent the DNA to the Joint Genome Institute. And then JGI turned on their genome sequencing muscle and sequenced the genomes of the organisms in the DNA samples. And finally, we spent a good deal of time then analyzing the data asking a pretty simple question - are there any general benefits that come from this "phylogeny driven" approach to sequencing genomes compared to what one might find with sequencing just any random genome (after all, any genome sequence could have some value)? The paper, describes what we found, which is that there are in fact many benefits that come from sequencing genomes from branches in the tree for which genomes are not available.

More on the details of the science below. But first, I want to note that this paper was truly an amazing team effort, with all sorts of people from the JGI in particular, going above and beyond the call of duty to make sure it happened and worked well. And the Department of Energy has been truly phenomenal in my opinion in supporting this project which in the end is not explicitly about "energy" per se but is really about providing a reference set of genomes that should improve the value of all microbial genome data.

Anyway, now for the story behind the story. And be prepared, because this is a bit long. But I think it is important to place this work in a bigger context both in terms of my background as well as some of the background of other people in the project. If you can't wait for more on the GEBA project then perhaps you should go to some of these links:

• Videos of talks I have given on the project:
• "Genomic Encyclopedia of Bacteria and Archaea (GEBA)"- Jonathan ...
• Recent talk I gave at the Sackler NAS "Microbes and Health" meeting
• Podcast of interview of me for ASM's Meet the scientist
• Stories about GEBA
• Nature News from 11.17.2009
• Stories about our paper
• Nature News
• GenomeWeb "GEBA Researchers Publish Results from Dozens of Bacterial, Archaeal Genomes"
• Ars Technica article "Presenting a genomic encyclopedia of bacteria (and archaea" by John Timmer
• Iddo Friedberg blogged about it
• The OpenHelix Blog on it
• Leonardo Martins blogs about it here and helps translate a Spanish story about the project
• R&D magazine has a post based on the press releases here
• NY Times story by Carl Zimmer here.
• FriendFeed Discussions here (includes a thread about Nature using a Creative Commons license)

And I will post more links as they come up. Below what I try to provide is some of the story behind the story:

My personal interest in applied uses of phylogenetics stage 1: undergraduate preparation at Harvard
As this paper is primarily about an applied use of phylogenetics (in selecting genomes for sequencing), I thought it would be worth going into some of how I personally became a bit obsessed with applied uses of phylogenetics. For me, my obsession began as an undergraduate at Harvard where I got exposed to the value of phylogeny as a tool from many many angles including but not limited to:

• Freshman year taking a course taught by Stephen Jay Gould where Wayne and David Maddison were Teaching Assistant's and where they were demoing their new phylogenetics software called MacClade
• Sophomore year taking a conservation biology class with Eric Fajer and Scott Melvin where I was exposed to the concept of "phylogenetic diversity" as a tool in assessing conservation plans
• Junior year working in the lab of Fakhri Bazzaz with people like David Ackerly and Peter Wayne who made use of phylogeny as a key tool in their research projects
• Senior year and the year after graduating where I worked in the lab of Colleen Cavanaugh using rRNA based phylogenetic analysis to characterize uncultured chemosynthetic symbionts. I note it was in Colleen's lab that I also became obsessed you could say with microbes and why they rock.

My personal interest in applied uses of phylogenetics stage 2: graduate school at Stanford

All of this and more gave me a strong passion for phylogeny as a tool. And so when I went to graduate school at Stanford (originally to work with Ward Watt on butterflies, but then I switched to working in Phil Hanawalt's lab on the "Evolution of DNA repair genes, proteins and processes"). And while in that lab I become pretty much obsessed with three things, all related to phylogeny.

First, I was interested in whether the rRNA tree of life, which I had used in my studies in Colleen Cavanaugh's lab (and in my first paper in J. Bacteriology, which, thanks to ASM, is now in Pubmed Central and free at ASM's site too), was robust or, as some critics argued, was not that useful. This was a critical question since the best way to study the phylogeny of microbes at the time, and also the best way to study uncultured microbes, was to leverage the ability to clone rRNA genes by PCR and then to build evolutionary trees of those rRNA genes. As part of my graduate work, I did a study where I compared the phylogenetic trees of rRNA to trees of another gene from the same species (I chose, recA). Surprisingly, despite the claims that the rRNA tree was not very useful and that different genes always gave different trees, if you compared the two trees ONLY where there was strong support for a particular branching pattern, the trees of the two genes were in fact VERY VERY similar (a finding that had been suggested previously by others, including Lloyd and Sharp)

Second, I also became obsessed with the fact that most of the experimental studies of DNA repair processes were in a very narrow sampling of the phylogenetic diversity of organisms (e.g., at the time, no studies had been done in archaea, and most studies in bacteria were from only two of the many major groups). So I started experimental studies of repair in halophilic archaea in order to help broaden the diversity of studies. And I began to use PCR to try and clone out repair genes from various other species of diverse bacteria and archaea. Alas, as I was doing this, some institute called TIGR was sequencing the complete genomes of organisms I was trying to clone out single genes from. In fact, one of the first organisms I was working on for PCR studies was Archaeoglobus fulgidus. And when I found out TIGR was sequencing the genome, in a project led by non other than the great microbial evolutionary biologist Hans-Peter Klenk (yes, the same one who helped us in this GEBA project). I decided it was silly to try to clone out individual genes by PCR. And thus I began to learn how to analyze genomes.

It was in the course of learning how to analyze genomes that I came up with another applied use of phylogeny. I realized that one should be able to use phylogenetic studies of genes to help in predicting functions for uncharacterized genes as part of genome annotation efforts. And so I wrote a series of papers showing that this in fact worked (I did this first for the SNF2 family of proteins and then alas coined my own omics word "phylogenomics" to describe this integration of genome analysis and phylogenetics and formalized this phylogenomic approach to functional prediction). I note that what I was arguing for was that protein function could be treated like ANY other character trait and one could use character trait reconstruction methods (which I had learned about while playing with that MacClade program) to infer protein functions for unknown proteins in a protein tree. I note that this notion of predicting protein function from a protein tree is completely analogous to (and one could rightfully say stolen from) how researchers studying uncultured microbes were trying to infer properties of microbes from the position of their rRNA genes in the rRNA tree of life (as I had learned in studies of symbioses).

My personal interest in applied uses of phylogenetics stage 3: my plans for a post doc

So as I was wrapping up graduate school I was seeking a way to go beyond what I was doing and combine studies of DNA repair and evolution and microbiology in another way. And I thought I had found a perfect one in a post doc I accepted with A. John Clark at U. C. Berkeley. John was the person who had discovered recA, the gene I had been using for phylogenetic analysis and for structure function studies. And he was working with none other than Norm Pace and a young hotshot in Norm's lab, Phil Hugenholtz (as well as a few others including Steve Sandler) in trying to use the recA homolog in archaea as a marker for environmental studies of archaea. It sounded literally perfect. And so I was excited to start this job. That was, until I met Craig Venter.

Grabbing the TIGR by the tail

While I had been playing around with data from TIGR in the latter years of my time in graduate school, I also got involved in teaching a fascinating class with David Botstein, Rick Myers, David Cox and others. (As an aside, this class was part of a new initiative I helped design at Stanford on "Science, Math and Engineering" for non science majors - an initiative that was a pet project of non other than Condie Rice who was Provost at the time). Anyway, Rick Myers was serving as a host for one Craig Venter when he came and gave a talk at Stanford and somehow I managed to finagle my way into being invited to go out to dinner with Craig. And at dinner, I proceeded to tell Craig that I thought some of the evolution stuff he was talking about was bogus and I tried to explain some of my work on phylogeny and phylogenomics. Not sure what Craig thought of the cocky PhD student drawing evolutionary trees on napkins, but it eventually got me a faculty job at TIGR and I worked extensively with Craig so it must have been worth something. And so I and my fiancé Maria-Inés Benito (now wife ...) moved to Maryland and spent eight great years there (my wife started in MD as a faculty member at TIGR too, but then she left to go to a company called Informax, may it rest in peace).

Most of my work at TIGR focused on a different side of phylogenomics than represented in the GEBA project. At TIGR I focused on the uses of evolutionary analysis as a component to analyzing genomes - from predicting gene function to finding duplications (e.g., see the V. cholerae genome paper) to identifying genes under unusual patterns of mutation or selection to finding organelle derived genes in nuclear genomes (e.g., see this) to studying the occurrence of lateral gene transfer or the lack of occurrence of it to studying genome rearrangement processes.. And sure, every once in a while I worked on a project where the organism was the first in its major branch to have a genome sequenced (e.g., Chlorobi). And I had noted, along with others that there was a big phylogenetic bias in genome sequencing project (e.g., see my 2000 review paper discussing this here).

But that did not really drive my thinking about what genome to actually sequence until TIGR hired a brilliant microbial systematics expert Naomi Ward as a new faculty member. And it was Naomi who kept emphasizing that someone should go about targeting the "undersequenced" groups in the Tree of Life.

NSF Assembling the Tree of Life grant
And so Naomi and I (w/ Karen Nelson and Frank Robb) put together a grant for the NSF's "Assembling the Tree of Life" program to do just this - to sequence the first genomes from eight phyla of bacteria for which no genomes were available but for which there were cultured organisms. Amazingly we got the grant. And we did some pretty cool things on that project, including sequencing some interesting genomes, and developing some useful new tools for analyzing genomes (e.g., STAP, AMPHORA, APIS). And I was able to hire some amazing scientists to work in my lab on the project including Dongying Wu (the lead author on the GEBA paper) and Martin Wu (who also worked on the GEBA project and is now a Prof. at U. Virginia) and Jonathan Badger. Alas, we did not publish any earth shattering papers as part of this NSF Tree of Life project on analyzing the genomes of these eight organisms, not because there was not some interesting stuff there but for some other reasons. First, I moved to UC Davis and there was a complicated administrative nightmare in transferring money and getting things up and running at Davis on this project so my lab was not really able to work on it for two years (in retrospect, what a f*ING nightmare dealing with the UC Davis grants system was ...).

Then, just as things we ready to get restarted, TIGR kind of imploded and many of the people, including Naomi, my CoPI, left (though I note, my moving to Davis was unrelated to the dissolution of TIGR). But perhaps most importantly, there were some actual technical and scientific problems with our dreams of changing the world of microbiology from our phyla sampling project - the science was not quite there. In particular, having a single genome from each of these phyla was simply not enough to get (and show) the benefits that can come from improved sampling of the tree of life. And thus though we have published some cool papers from this project (e.g., see this PLoS One paper on one of the genomes), we all ended up in one way or another, disappointed with the final results.

Davis and JGI: the return of phylogeny to genomic sampling

When I moved to UC Davis I also was offered (and accepted) an Adjunct Appointment at the Joint Genome Institute (JGI). At both places, I envisioned reinventing myself as someone who worked on studying microbes directly in the environment (e.g., with metagenomics) and symbioses (both of which I had started on at TIGR). And in fact, in a way, I have done this, since I got some medium to big grants to work on these issues. I tried diligently to attend weekly meetings at the JGI but it was difficult since technically I was 100% time at UC Davis and was in essence supposed to be at 0% time at JGI. And when JGI hired Phil Hugenholtz to run their environmental genomics/metagenomics work, I was needed less at JGI since, well, Phil was so good. It was great to go over there and interact with Eddy Rubin, Phil Hugenholtz, and Nikos Kyrpides, among others, but it was unclear what exactly I would do there with Phil running the metagenomics show.

And then, like magic, something came up. I went to one of the monthly senior staff meetings at JGI and while we were listening to someone on the speaker phone, Eddy Rubin handed me a note asking me what I thought about the proposal someone was making to sequence all the species in the Bergey's Manual. And the light bulb of phylogeny went back on in my head. I told him (I think I wrote it down, but may have said out loud), something like "well, sequencing all 6000 or so species would be great, but it would be better to focus on the most phylogenetically novel ones first." And in a way, GEBA was born. Eddy organized some meetings at JGI to discuss the Bergey's proposal and I argued for a more phylogeny driven approach. And this is where having Phil Hugenholtz and Nikos Kyrpides at JGI was like a perfect storm. You see, both had been lamenting the limited phylogenetic coverage of genomes for years, just like I had. Phil had even written a paper about it in 2002 which we used as part of our NSF Tree of Life proposal. And Nikos too had been diligently working for years to make sure novel organisms were sequenced. So though we went to a meeting to discuss the Bergey's manual idea, we instead proposed an alternative - GEBA.

And for some months, we pitched this notion to various people including at JGI, DOE, and various advisory boards. And the response was basically - "OK - sounds like it COULD be worth doing - why don't you do a pilot and TEST if it is worth doing" And so, with support from Eddy Rubin and DOE, that is what we did.

One key limitation - getting DNA

So Phil, Nikos and I and a variety of others starting working on the general plan behind GEBA. But there was one key limitation. How were we going to get DNA from all these organisms? One possibility was to seek out diverse people in the community and have them somehow help us. This had some serious problems associated with it, not the least of which was the worry that we might end up sequencing varieties of organisms that people had in their lab but which nobody else had access to (something Naomi Ward and I had written about as a problem a few years before).

And here came the second perfect storm - none other than Hans-Peter Klenk (yes, the same one who had led some of the early genome sequencing efforts when he was at TIGR), was visiting JGI. And he had a relatively new job - at the German Culture Collection DSMZ (In fact, I should note, I had tried to get a job at TIGR even before I met Venter, since they had a position advertised for a "microbial evolutionary biologist" --- but that job went to Klenk). Phil Hugenholtz had asked the Head of DSMZ, Erko Stackebrandt, if they might be interested in helping us grow strains and get DNA but we did not yet have a full collaboration with them. And Erko had suggested we contact Hans-Peter. And in his visit to JGI it became apparent that he would do whatever he could to help us build a collaboration with DSMZ. And thus we had a source of DNA. Even more amazingly to me, they did it all for free.

GEBA begins

And thus began the real work in the project. Phil used his expertise with rRNA databases, especially GreenGenes, to pull out phylogenetic trees of different groups. And Nikos used his expertise as the curator of a database on microbial sequencing projects (called GenomesOnline) to help tag which branches in Phil's tree had sequenced genomes or ones in progress. And then they looked for whether any of the members of the unsequenced branches had representatives in the DSMZ collection. And with some help from Dongying Wu and me, we came up with a list. And with the help of the JGI "Project Management" team including David Bruce and Lynne Goodwin and Eileen Dalin and others at JGI we developed a protocol for collaborating with DSMZ and getting DNA from them.

And I became the chief cheerleader and administrator of the project, in part since Phil and Nikos were so busy with their other things at JGI. And though I was not always on the ball, the project moved forward and we started to get genomes sequenced using the full strength of the JGI as a genome center. The finishing teams at JGI worked diligently on finishing as many of the genomes as possible. And Nikos' team at JGI made sure that the genomes were annotated. And I helped make sure that they data release policies were broadly open (which everyone at JGI supported). And after many false starts with papers on the project that were way way way to cumbersome and big, with some kicks in the pants from the director of JGI Eddy Rubin who was getting anxious about the project, we turned out the GEBA paper that was published today in Nature.

You might ask, why, as a PLoS official and PLoS cheerleader, we ended up having a paper in Nature? Well, in the end, though I am senior author on the paper, the total contribution to the work mostly came from people at JGI who did not work for me but instead worked with me on this great project. And we took some votes and had some discussions and in the end, despite my lobbying to send it to PLoS Biology, submitting it to Nature was the group decision. I supported this decision in part due to the fact that Nature uses a Creative Commons license for genome papers. But I also supported it because in the end, this was a collaboration involving many many many people and in such projects everyone has to compromise here and there. Now mind you, I am not sad to have a paper in Nature. But I would personally have preferred to have it in a journal that was fully open access, not just occasionally open like Nature.

Now I note, there were a million other things that went on associated with the GEBA project. Some of which I was not even involved in in any way. I will try to write about some of these another time, but this post is already way way way too long. So I am going to just stop here and add that I have been honored and lucky work with people like Phil, Nikos, Hans-Peter, and others on this project and to have the people at the JGI work so hard on the background parts of this project. Thanks to all of them and to the people at DSMZ and in my lab who helped out and to the DOE for funding this work (as well as the Gordon and Betty Moore Foundation, who funded some of the work from my lab on analysis of these genomes). And last but not least, thanks to the Director of JGI Eddy Rubin, supporting this project and for being patient with it and for kicking us in the pants when we needed to get moving on getting a paper out.

Wu, D., Hugenholtz, P., Mavromatis, K., Pukall, R., Dalin, E., Ivanova, N., Kunin, V., Goodwin, L., Wu, M., Tindall, B., Hooper, S., Pati, A., Lykidis, A., Spring, S., Anderson, I., D’haeseleer, P., Zemla, A., Singer, M., Lapidus, A., Nolan, M., Copeland, A., Han, C., Chen, F., Cheng, J., Lucas, S., Kerfeld, C., Lang, E., Gronow, S., Chain, P., Bruce, D., Rubin, E., Kyrpides, N., Klenk, H., & Eisen, J. (2009). A phylogeny-driven genomic encyclopaedia of Bacteria and Archaea Nature, 462 (7276), 1056-1060 DOI: 10.1038/nature08656