Revisionist history at EPCOT

Several news blogs, including BoingBoing, have reported that the new refurbished "Spaceship Earth" ride at EPCOT now includes a diorama of Wozniak's and Jobs' garage where Apple got its start in the mid 1970s. Very nice. But take a look at the computer that one of the Steves (presumably Wozniak, the more technical of the two) is working on -- is it an Apple I, the computer that was actually designed in the garage? No -- it seems to be some sort of fictional primitive Lisa or Macintosh -- machines that weren't designed until years later. Why, oh why? Are they planning an diorama with Henry Ford building a primitive Taurus?

The Internet doesn't lie...

My immunologist friend Andreas Krueger has recently pointed out to me that according to a certain website the reading level of this blog is "Genius". I'm sure this is every bit as scientific as those quizzes that tell you which Star Wars character you are most like. Also, this ranking was made prior to this post -- it would be amusing if this post somehow weakened the rating...

A Life Decoded: My Genome: My Life

First of all, I'll get the required whining over the title done with -- yes, RPM, myself, and TR Gregory all have written about our annoyance with the terms "decoded/deciphered/cracked" in relationship to genomes, but there's a good chance that the title was thought up by the publisher. I would have called it "A Life in Sequence", but oddly enough, nobody asked me.

Now that that's done, how was the book? Pretty good (and I'm not just saying that because Craig's my ultimate boss and could fire me, honest -- he'd have to know who I was, for starters). It's a bit snarky in places, and some of his opponents come off as caricatures, but it's entertaining in much the same way as The Double Helix was.

The book is written as an autobiography, with bits of relevant genome information inserted in -- the gimmick is that this is the first of many "molecular (auto)biographies" that will interpret lives in the context of genomic sequences and the alleles the subject carries. Right now, it is a gimmick (although an amusing one), but I can see how in the future it might really be informative.

Much of Craig's working class youth and experience in the Vietnam War have been covered by various media stories before, but it is nice to hear it straight from Craig -- for one thing, it clears up the confusion between the shark and sea snake stories -- often these anecdotes are wrongly merged into one story.

What was new to me was learning about his pre-genomics scientific career. I had no idea that Craig's background was in biochemistry, for example. He credits that with helping him getting the early (notoriously temperamental and unreliable) automated sequencing machines to work when others, mostly from genetics and molecular biology backgrounds, couldn't.

The book is also interesting for some rather open and telling quotes -- probably my favorite is

One of my critics, John Sulston, objected that I wanted to have it both ways: "to achieve recognition and acclaim from his peers for his scientific work, but also to accommodate the needs of his business partners for secrecy and enjoy the resulting profits". I plead guilty, along with the rest of humanity, to committing the most heinous crime of both wanting my cake and eating it.

The rest of humanity indeed. Later Craig shows that many in the "holier-than-thou" public genome project also had links to the biotech industry; their primary difference from Craig seems to be that they tended to hide their conflicts of interest rather than openly declaring them.

Some of Craig's interpretations may be a little off base -- at one point Craig prides himself for not having the tenure system at his institutes on the basis that "the second rate people who thrive in a tenured environment like nothing more than to surround themselves with more mediocrity and drive out those who might excel and reveal the shortcomings of the entrenched". Well, perhaps. But the simpler explanation might be that tenure is rather hard to give when everyone is working off soft money which could disappear in the next funding cycle. And there has to be more to the story that Claire was the one who suggested merging JCVI and TIGR. In what context?

But in general, Craig's observations are dead on. Venter's opponents have tried to spread the myth that he's out to be "the Bill Gates of Biology", and whatever faults the guy has, his motivations are a lot more complicated than just the pursuit of money. Shreeve's "The Genome War" covered some of this, but it is nice to finally hear Craig's story from himself.

The Third Domain

Tim Friend's recent book The Third Domain is an odd book on two levels -- first of all, the story that one would think it tells, that of Carl Woese's discovery of the Archaea, the initial hostile reaction that the discovery met with at the hands of the scientific establishment, and its eventual acceptance by the majority -- makes up only one chapter (chapter 3) of the book. The rest of the book mostly follows field microbiologists like Karl Stetter and Eric Mathur as they collect samples (often, but not always, of archaea) from hot springs and thermal vents. Secondly, rather than being one unified whole, each chapter reads as its own story (which it may well have been; Friend is a former USA Today science writer and may be simply fleshing out articles he's already written). I'm of two minds about this book; as a evolutionary microbial genomicist (and one who has had the honor of working with Woese), I'm glad that there's a new book for the general public that acknowledges that microbes are worth studying for things other than their effect on human health; but on the other hand, I can't help but wonder if the story of the Archaea couldn't have been told in a more engaging manner. Bill Bryson, in his A Short History of Nearly Everything managed to tell Woese's story (if a bit too simplified) in an exciting chapter there. In conclusion, The Third Domain is worth a read (especially if you are interested in the subject), but the definitive book on Woese and the archaea has yet to be written.

Biologists are happier than Computer Scientists

A recent survey conducted by the National Survey on Drug Use and Health (NSDUH) compared the percentage of US workers reporting an MDE (Major Depressive Episode) in the past year across occupation, gender, and age. Some of the results were fairly predictable, such as food and service workers having a greater than average occurrence of MDEs, and I had read before that women and older people tend to be more depressed on average, but some of the other results were quite surprising, at least to me. For example, "Mathematical and Computer Scientists" had a considerably higher rate (6.2%) of MDEs than did "Life, Physical, and Social Scientists" (4.4%). Not sure where that leaves bioinformaticians....

GME 2007 Highlights

Well, I haven't blogged much lately, but there hasn't been much coverage of last week's GME 2007 (no, not this GME 2007!), other than Jonathan Eisen's brief live comments, so I figured it might be of interest to talk about some of the talks I attended there.

GME (Genomes, Medicine, and the Environment) is the meeting that was once called GSAC (Genome Sequencing and Analysis Conference), with the name change reflecting that the focus is now more on the use of genomics to understand medicine and the environment rather than on genome sequencing per se (although there was still a session on sequencing technology). It was held in San Diego, which allowed me to visit the La Jolla branch of the JCVI and to see former colleagues who have transplanted to the “left coast”.

Colleen Cavanaugh and Nancy Moran gave interesting back-to-back talks on bacterial symbionts of plants and animals and brought up many of the same issues in their evolution – namely that the genome size of symbionts seems to be correlated with the estimated age of their relationship with their host – that is that large bacterial symbiont genomes seem to shrink over time. Not that this is surprising, given that mitochondria and plastids are thought to be remnants of symbionts with larger genomes, but it is nice to see evidence of the process in progress today. The isolated environment of symbionts also seems to result in other oddities, such as increase levels of drift and chance fixation. As I am currently involved in a genome project of an endosymbiont of a cellulose-degrading shipworm, both Nancy's and Colleen's talks gave me many ideas for interesting things to look for.

JCVI's own Nobel laureate, Ham Smith, gave a pleasantly low-key talk on the status of his synthetic life project (no, bad scientific reporting to the contrary, he hasn't succeeded yet). Basically, now that his group has successfully transferred a genome from one bacterium to another, they are building an entire synthetic genome of Mycoplasma genitalium from scratch. Of course, even when they successfully transfer this they won't really have “synthetic life”, but it is clearly a step that needs to be done along the way. Again, I really liked it how Ham basically just said what he was doing without any hype – but then, when you have the Nobel, I guess you don't need hype.

A younger JCVI researcher, Yuri Gorby, presented his work on “nanowires” -- basically, structures produced by some bacteria that conduct electricity. The theory is that these allow the bacteria to disseminate electrons in a biofilm, thus freeing the bacteria from having to have direct contact with an electron acceptor. Really cool stuff, although not universally accepted yet.

Edward Bayer gave a talk about the “cellulosome”, which I hadn't heard of before, but given that I'm working on a cellulose degrading bacterium, I suppose I should have. Basically, not all cellulases are free in the cytoplasm – basically many form a complex (the aforementioned “cellulosome”) which is far more efficient than free cellulases. As Jonathan Eisen mentioned, Edward's paraphrase of Genesis at the start of the talk did seem rather off-putting, but hopefully it's just a cultural thing – perhaps in Israel such talk is just a manner of speaking and not a sign of creationism. He did mention evolution at one point, which was somewhat reassuring.

My former TIGR colleague John Heidelberg gave a talk on his work on metagenomics of cyanobacterial mats in Yellowstone Park hot-springs. Besides the interesting results, he brought up the important (if somewhat scary) observation that it is possible to assemble a genome from metagenomic data that doesn't actually exist in nature (much like nobody has the average 2.2 children).

Gene Tyson and Mary Ann Moran both talked about “metatranscriptomics”, which despite being a new “omics” (another one? geez!), is actually a really good idea – don't just sequence genomes from the environment – sequence the mRNAs to get an idea of what genes are turned on in a population in a given condition. Tyson was using microbial data from the Hawaii Ocean Time-series station ALOHA, and Moran was looking at her coastal Roseobacters.

Jonathan Eisen talked about his “Genomic Encyclopedia” which he plans to do with the JGI. Basically he plans to sequence (in a high throughput manner) hundreds of bacteria and archaea He aims to start with a pilot of 200 organisms (100 of which he'll close), but there's talk of maybe doing everything in Bergey's manual. From Jonathan's perspective, the point is to make a “happy tree of life” in which we have data to make truly representative phylogenetic analyses. As a genomicist, I find this both awesome and scary. Obviously, I'd love to have the data, but it looks like the time of “genome projects” as such is becoming as quaint as cloning and sequencing a single gene. Well, times move on, I suppose. Jonathan also talked about our Hyphomonas work as an example of how genomics helps resolve phylogenetic questions.

Shannon Williamson (now of JCVI-La Jolla) presented a talk about phage metagenomics in deep sea environments. Basically, she found that bacteria in diffuse-flow thermal vents have more lysogenic phages than do bacteria in the surrounding cold water (presumably because lytic phages would have have a hard time finding a host in a diffuse environment). Additionally, the phages are less diverse than in the surrounding waters, This talk was especially interesting to me because I helped her with some of the bioinformatics analyses, but I hadn't seen the big picture before.

Horizontal Gene Transfer from Bacteria to Eukaryotes

Can bacteria transfer genes to eukaryotes? Many people may remember the rather rash assertion of evidence that they can that was made in the initial human genome paper (and the subsequent debunking of those claims by people I used to work with at TIGR).

But just because one study was flawed doesn't mean that such horizontal transfers don't happen, and today in the advance publication section of Science a new study shows solid evidence that the endosymbiotic bacterium Wolbachia has integrated parts (in some cases quite large portions) of its genome into that of numerous strains of Drosophila, the wasp Nasonia, and the worm Brugia malayi. These aren't mere cases of "BLASTology" -- they were confirmed by PCR. Even more stunningly, RT-PCR suggests that in some cases the integrated genes are actually expressed.

Again, there is a TIGR/JCVI connection -- one of the co-first authors, Julie Dunning Hotopp, has a cube only several feet from mine -- and all today I could hear her talking on the phone with science reporters -- so congratulations to her (and best wishes that the reporters don't screw things up). Also, congratulations to all the other authors, particularly the other co-first author, Michael Clark, whom I haven't met.

The results of the study have many implications both theoretical and practical. From an evolutionary perspective, it is interesting to ponder if the ancestors of many current eukaryotic genes came from such bacterial integrations. And from a practical perspective, it really makes one wonder if discarding bacterial sequences during the assembly of eukaryotic genomic data as "obvious contamination" (as is commonly done) is really the right thing to do.

Into the Great Wide Open

My mother has spent the past 25 years working in the field of association management. What's that, you might ask? Well, if you're a scientist you probably belong to one or more associations such as the American Society for Microbiology (ASM). And it isn't just science; most professional fields have such organizations. There's even the American Society of Association Executives (ASAE), to which the people (such as my mom) who run the other associations belong. Associations, regardless of their topic, tend to fulfill the same functions, one of which is publishing journals. And that leads me into the topic of this posting.

My mother recently sent me a hardcopy of an article from ASAE's "Associations Now" magazine. It's entitled "Into the Great Wide Open" and it consists of an interview of Patrick Brown, one of the co-founders of PLOS. It is really significant that a publication of the ASAE would run such an article, because traditionally, the enemies of open access have not just been commercial publishers like Springer and Elsevier, but also many non-profit associations with publishing divisions. So I was expecting a hostile attack on open access, but actually it's quite a fair interview. In fact, they even printed the following exchange:

One thing that you've mentioned several times and I think is a big concern for the society publishers—especially societies that use income from their journal to subsidize other aspects of what they do for their members—is financial sustainability. What can you tell association publishers to show them that this transition can be sustainable?

There's a bunch of issues there. Number one, a lot of societies that make that claim—I would encourage people to look at their Form 990s. I get great enjoyment out of reading the Form 990s of scientific societies that talk about how important it is to preserve the income from their journals to do all these wonderful things they do, when, very often, the wonderful things they do, taken in aggregate, don't add up to the cost of their chief executive officer.

But let's just take that at face value—that their only motivation is to do good for the world and for science and for their community. One of the questions is, how important are those things that you're trying to fund with profits in your journal, compared to the good that you do for your mission through publishing itself and making access as freely available as possible?

The whole interview is interesting reading. And don't miss the informative sidebar containing a glossary of various Open Access terms. I have to admit I have a hard time remembering what the Berlin Declaration, etc. are, and I imagine most people who aren't professionally involved in the Open Access movement do too.

ISMB 2007 Vienna -- Part II Interesting Talks

I'd just like to comment on some talks that I also found particularly noteworthy or interesting.

Atul Butte gave an interesting talk on nosology. No, that's not the study of noses, but rather the classification of diseases. What Butte has done is cluster gene expression patterns from various diseases. And the results were surprising. For example, he discovered that cervical cancer expression clustered with that of an autoimmune disease andmuscular dystrophy clustered with some forms of heart disease. These connections were unexpected and may lead to better understanding of these diseases. I liked the idea (even though I am not normally a disease person) because I found the idea analogous to the way unexpected phylogenetic relationships can be informative.

Christian von Mering talked about phylogenetic analysis of samples from metagenomics projects. He is interested in this problem because contrary to what was generally believed prior to environmental sequencing, specific microbial species (& higher taxonomic levels) are not found everywhere it would be possible for them to live -- in other words, microbes have meaningful biogeography, just like plants and animals. Von Mering and colleagues have created an interesting pipeline for the interpretation of metagenomic data. Rather than try to analyze each of the millions of reads in detail, his method first identifies standard phylogenetically informative marker genes, then adds them to existing high quality alignments, and uses a custom phylogenetic program to test all possible phylogenetic positions on a reference tree. Both the limitation to markers and the custom phylogenetic component make this pipeline much more efficient than the typical phylogeny based methods.

Haipeng Li talked about a new maximum likelihood method for inferring positive selection and demographic history from chromosome-wide SNP data. His test case was Drosophila melanogaster and according to his model, the European population split off from the African lineage 16,000 years ago and underwent some sort of bottleneck. Current low levels of X-linked diversity (as opposed to the autosome) in the European population suggests a large excess of males in this population. This latter assertion was questioned by several members of the audience as it doesn't seem to be congruent with empirically measured numbers of males in the wild. Still, I find such studies fascinating. I would love to do a similar demographic study using bacteria, but I doubt we have enough data, even for things like E. coli or Bacillus anthracis.

And Alissa Resch, who works at the NCBI (just down the road from JCVI), also gave an interesting talk about positive selection. Odd that I'd have to travel thousands of miles to hear it though. Resch developed a new statistical test for positive selection that uses the rates of synonymous substitution in nearby intronic regions as a background. This allows detection of positive selection even at synonymous sites. She then applied it to orthologous gene pairs in mouse and rat.

ISMB 2007 Vienna, Part I - Keynotes

I realize that I'm a bit late in covering a conference that occurred July 21-25, but I combined the conference with post-conference trips to Prague, Leipzig, and Berlin and have been busy at work since returning to Washington earlier this week.

There doesn't seem to have been much coverage of ISMB 2007 in the blogosphere (I've only found the coverage at Suicyte Notes,
and Fungal Genomes -- a few others had humorous posts about misadventures getting to Vienna, etc., but didn't cover any of the talks -- let me know if I missed any science-related postings).

In this first posting, I'll talk about my impressions of several of the keynote talks that made the most impression on me.

First of all, there was Michael Eisen's talk. Having worked with his brother, Jonathan, for some years, it was fun to finally see (and after the talk, briefly meet) the "other" Eisen. As would be expected from Mike's papers, his keynote largely dealt with the evolution of regulatory sequences in Drosophila. In the midst of this he made an offhand comment which generated both cheers and boos from the audience to the effect that bioinformaticians should stop working on microarray analysis methods "as nobody will be using microarrays in a couple of years". Well, we'll see.

Then, there was John Mattick's talk, which made me angry. Not because I disagree with his assertion that our traditional picture of gene regulation is incomplete, and that non-coding RNA-mediated gene regulation is going to be an important part of our revised picture, but I found his attitude towards non-eukaryotes (and even just non-mammals) annoying. According to John, the reason why "prokaryotes" are "simple" is that their gene regulation is just protein-based, while "higher organisms" require the use RNA as well. He even had graphs where "complexity" (how exactly is that defined objectively, now?) was the y-axis -- humans at the top, of course -- just like the medieval "Great Chain of Being" (minus the superhuman levels). The simple fact is that RNA based regulation isn't just limited to eukaryotes - non-coding RNA has been shown to be important in bacteria and archaea as well. Our picture of gene regulation in all domains of life is changing. Those on the quixotic quest to show that the evolutionary branch leading to humans is somehow "special" will have to look elsewhere.

And then there was Terry Speed's talk, which was one of those "historical" talks that some people see as a waste of time. Maybe it's because I once seriously considered becoming a historian of science, or perhaps it's just that I'm getting old, but I like such talks. And I learned a lot from it. For example, I always assumed that HMMs first entered biology from computer science in the context of sequence analysis/gene finding in the early 1990s, but Terry showed how people in pedigree analysis (including, if I recall from the talk, Eric Lander in his pre-genomics career) brought them into biology earlier.

I will write further on ISMB in subsequent posts.

British accused of releasing badgers in Iraq

This article was from the BBC, and not the Weekly World News, I swear! The article (with the catchy, alliterative title British blamed for Basra badgers) claims, "British forces have denied rumours that they released a plague of ferocious badgers into the Iraqi city of Basra.". Of course, at first glance, this denial seems implausible -- what better way to solve the insane quagmire of Iraq than releasing badgers with the idea that chaos counteracts chaos? On the other hand, apparently the supposed badgers are not the noble Taxidea taxus, but apparently mere "honey badgers" (Mellivora capensis).

Anyone attending ISMB 2007 in Vienna?

Anyone atttending the bioinformatics conference ISMB 2007 (held in Vienna, Austria this year)? I'll be there, along with several fellow alumni of the bioinformatics group from Waterloo -- John Tsang, Tomas Vinar, and Broňa Brejová. Perhaps we could organize a bloggers' dinner or something there if we get a critical mass.

Tagged!

Well, just a few days after I did a "Friday Cat Blogging" (sort of), I find that there's another blogging tradition that I need to follow -- that of a "tagged post". I've been tagged by John Logsdon to follow up on his "eight random facts about yourself" posting and tag eight other bloggers with the same meme.

The rules are:

1. We have to post these rules before we give you the facts.
2. Players start with eight random facts/habits about themselves.
3. People who are tagged need to write their own blog about their eight things and post these rules.
4. At the end of your blog, you need to choose eight people to get tagged and list their names.
5. Don't forget to leave them a comment telling them they're tagged, and to read your blog.

1. I am a native Wisconsinite and my last name is indeed "Badger" (as Wisconsin is known as the 'Badger State', the sports teams of the University of Wisconsin are the 'Badgers' and so many businesses there are named Badger this and Badger that, this was the source of many jokes growing up). Apparently my name has no linguistic connection to the animal or state, though -- 'Badger' is a Scots name and my father's ancestors were Scots-Irish.


2. I don't drive. In the Midwest this fact generally generates gasps of incredulity, here on the East Coast it often generates compliments on the assumption that I've done it out of some noble principle, protesting urban sprawl or pollution or something. But really, given my poor eyesight, reflexes, and sense of direction, it's just better for everyone (including myself) that I stay off the road.


3. My scientific genealogy includes two Nobel Laureates (Rutherford and Chadwick) and well as a winner (Woese) of the Nobel-ish award for evolutionary biologists/ecologists, the Crafoord Prize in Bioscience. Not that that necessarily means anything for my own career -- as stock brokers say, "past performance is no guarantee of future returns".


4. I like languages. Both computer and human. The computer languages I know are Basic, Pascal, C, C++, Smalltalk, Forth, dBASE, Actor, Perl, and Ruby. The human languages I know are English, Esperanto, French, and German, although to be honest, I'm far better at reading than speaking the last two.

5. As if it wasn't obvious from my "Friday Cat Blogging", I'm a cat person. I don't much care for dogs. I find the large ones vaguely threatening, and the small yippy ones are just plain annoying. Plus, they neither clean themselves nor use a litter box. Human infants have similar defects, but I guess inclusive fitness must play some role because all the people I know with infants seem to overlook this.


6. I seem to have an obsession about the former East Germany. I own 27 books about East Germany and listen to albums like "Die Partei hat immer recht" and collections of Oktoberklub songs.



7. My favorite authors are John Crowley and A.S. Byatt. Besides the fact that they both write well, they both seem to be attracted to the Elizabethan and Victorian eras. These eras also attract me because they were also transitional times in the history of science -- the dawn of modern science in the early 1600s and the transition of science from hobby of the independently wealthy to practical career choice in the late 1800s.



8. I like my coffee black, and my art nerdy (Escher) or atmospheric (Hopper).






I tag:
Jacques Ravel
Neil Saunders
Eva
Steve Salzberg
Mike Hu
Naomi Ward (yes, your blog has to rise again!)
John Tsang (You need a blog!)
Marei Dose (ditto)

My 15 minutes (or 30 seconds) of fame

I've worked with people like Carl Woese and Jonathan Eisen who routinely get interviewed by the media, but this is the first time that I've been in the spotlight. In May, Chris Condayan interviewed me along with several other bloggers attending the ASM 2007 meeting in Toronto, and he's edited them into an edition of his MicrobeWorld series dealing with microbiologists who blog.

Besides me, the featured bloggers are John Logsdon, "Yersinia", Tara Smith, Elio Schaechter, and Larry Moran.

Tara seems to think that she is too "animated", but I think she is undervaluing the value of animation. After all, this week, the animated Ratatouille beat out the latest "Die Hard" movie....

I could complain about my segment too, but it's probably pretty representative of me (not that I tend to talk into phones without calling someone first...)

Not your typical Friday Cat Blogging

There's a tradition in blogging culture termed "Friday Cat Blogging". in which bloggers post light-hearted articles on Fridays, with the clichéd example being pictures of one's cats. Well, as you can see, I did post a picture of Bella Cat Badger, perched upon my closet door as she so often is, but I actually have a more serious reason for bringing up the topic of cats this Friday -- Driscoll and colleagues newly published paper "The Near Eastern Origin of Cat Domestication" (probably not open access, unfortunately). Anyway, as the article involves both cats and phylogenetic inference, how could I resist?

Small wild cats live (or have lived) in many places in Europe, Africa, and Asia. So an obvious question is whether domestic cats in different parts of the world are more closely related to their local wild cats (evidence of independent domestication events in different parts of the world) or to wild cats from one part of the world. Driscoll and colleagues addressed the issue by two different methods: making a neighbor-joining tree from short tandem repeat (STR) profiling (basically DNA fingerprinting) of 979 cats and by making a maximum parsimony tree from the sequence of the ND5 and ND6 genes from the mitochondria of 742 cats. The cats contained a mixture of wildcats, feral domestic cats, and domestic cats of various breeds sampled from Europe, Asia, and Africa. Both analyses supported the conclusion that the closest ancestors of both European and Asian domestic cats are wildcats from the Near East. However, the mitochondrial data suggests that there are at least five maternal lineages within that group.

Secret Messages in DNA...no

There were a lot of blog postings about the evolution articles in yesterday's NYT (for example, JE's, Coturnix's and Larry's), but I don't recall anyone mentioning Dennis Overbye's article. I realize that making fun of bad science journalism is getting to be a rather repetitive joke, but this one is just weird. The article is combining two different topics. The first is about a Japanese group that encoded "E=mc^2" in DNA and introduced it into E. coli. That's a cute but in the end rather useless trick, rather like using DNA to solve cases of the traveling salesman problem (which people have also done). Apparently, the Japanese group seriously thinks that DNA in living organisms could be a practical data storage method, and claims that the problem of mutation could be solved be using multiple copies (which would only slow down the decay, not halt it).

It gets more disturbing in the second half -- apparently actually taking seriously the idea that messages could be hidden already (by aliens?) in our DNA. I mean, everyone is amused by finding phage proteins that actually contain the word "PHAGE" using single letter amino acid abbreviations, but that's different from actually assigning meaning to the coincidence. The numerous falsified "solutions" to the Voynich manuscript, the supposed Bible Code (and the facetious Moby Dick code), and the endless reinterpretations of Nostradamus suggests that people can find secret messages even when none exist. What's the point of encouraging such nonsense by even seriously considering it in a major newspaper? I expect a crank volume on messages in our genome any day now -- in fact, were I less scrupulous, I'd write it myself under a pseudonym -- I'm sure it would sell.

Greatest BBC Headline ever

"FBI tries to fight zombie hordes". Okay, I know the author knows he's being clever, and probably the people who actually have to deal with compromised Windows machines are already sick of the slang term "zombie", but still, I never expected to read such a Romero-esque headline at the BBC except maybe on April Fool's day.

Not that the zombies in the article affect me other than sending me more spam -- I'm a Linux and OS X user...

Genome of DNA Discoverer NOT Deciphered

Do you recognize the man in the picture? It's Friedrich Miescher, the Swiss biologist/biochemist who discovered DNA in 1869. So, when the NYT announced today that "Genome of DNA Discoverer Is Deciphered", I was really excited, despite the annoying (and incorrect) use of "decipher" to mean "sequenced". Just think! Sequencing the genomes of Victorian scientists is now in our grasp! Who will be next? Darwin? Maxwell? Faraday?

But alas, it isn't so. It's just Jim Watson's genome.

Craig Venter "plays God" on international editions of Newsweek

Apparently, on European, Asian, and Latin American editions of Newsweek this week, Craig Venter (my ultimate boss after about three levels), is shown looking, I suppose, reflective about the potential awesomeness of synthetic biology and the possibility of "playing God". Or maybe he just has indigestion. Anyway, the article is here. Interestingly enough, neither the cover nor the article appears in the US edition. The article is interesting enough, but I wish it would have clearly distinguished the public research on synthetic biology going on at the JCVI from Craig's startup. Yes, both involve Craig, but not everyone who works for Craig is on the private sector side of things.

ASM 2007 Wrapup

ASM 2007 ended at noon today. This morning I attended the session dedicated to the International Polar Year (March 2007-March 2008) in relation to microbiology. My favorite talk was by Corien Bakersman and it dealt with the cold adaptation in the psychrophile (no, it doesn't love psychos, they love cold - psychro) Psychrobacter articus. Interestingly enough, instead of identifying amino acid replacements (as in common in such studies), Corien looked for other trends. She discovered that ORFs in P. articus tend to be longer than in mesophiles and she sees that as being explained by selection for encoded proteins to be "floppy" thus preventing them from freezing up in cold temperatures. She also noticed the cell walls of P. articus tend to be less rigid than in mesophiles.

Pictured is Honest Ed's, a classic independent discount store (and Toronto landmark) that started back in 1948 by Ed Mirvish (who is still around, but 91 years old).

Highlights of ASM 2007 -- May 23 and May 24

On Wednesday, I attended two sessions -- one on adaptive landscapes in the morning and another on integrating ecology and evolution into the teaching of microbiology in the afternoon.

The highlight of the morning session was probably the talk by Paul Turner on the effect of co-infection on fitness variance in bacteriophage ϕ6 (which infects Pseudomonas). I hadn't heard about ϕ6 prior to this talk, but it is really quite interesting because much like the influenza virus, it is an RNA virus with multiple segments. When two or more ϕ6 phages infect the same cell, the progeny viruses can have a mixture of segments derived from different "parents". In theory, co-infection could act as a crutch for less fit viruses, as some of their (partial) progeny could be of higher fitness. Turner and colleagues showed that this indeed what happens An earlier version of the work he presented was written up in an article in PLoS Biology.

You might legitimately ask why I attended the afternoon session on integrating ecology and evolution into teaching microbiology (as I don't teach), but maybe I was just drawn to the name of Jo Handelsman, who is rightly renowned for both her teaching and her active research program. Jo is into metagenomics and microbial biodiversity these days, and she talked about how to explain the use of sampling to estimate diversity to undergraduates. She believes that it is easier to start out with concrete simple examples. One of her techniques is to use bags of candies that have different distributions of colors to show that one can underestimate diversity in populations with a majority species (If one draws out three candies and they are all green, one may be tempted to assume that all of the candies are green, perhaps incorrectly).

Thursday morning I had to attend my poster on positive selection in Geobacter. Most people stopping by were more interested in learning how to use PAML in their own systems than in the results, but that was okay as my results are fairly preliminary anyway.

In the afternoon, I attended a session on predation of bacteria. I've long been interested in predators of bacteria (particularly bacterial predators of bacteria such as Bdellovibrio). These days there is quite a battle going on over which of the three main predators (phage, protists, and bacterial predators) is the most important in regulation of bacterial populations in nature. Henry Williams (with whom last year I wrote a grant proposal to sequence environmental isolates of Bdellovibrio-like organisms, unfortunately not funded) gave an interesting talk on comparing the effects of phage versus Bdellovibrio-like predation. He came up with the conclusion that Bdellovibrio and friends are more important because their titers after controlled predation go up several orders of magnitude more than do phage, and this he explained as a result of Bdellovibrio being motile and phages not.

Mini-Blogger convention at ASM 2007

I promise I'll write something up on Wednesday's talks, but that would require too much thinking and it's getting late here. Instead, I'll just show this picture demonstrating that I've finally joined the cool blogging world for real. Larry Moran organized a dinner for bloggers attending ASM and invited me as well as other (mostly more established) bloggers. Pictured are (L to R), Larry Moran (Sandwalk), Mona (Science Notes), Andrew Staroscik (Mixotrophy), John Logsdon (Sex, genes and evolution), and Tara Smith (Aetiology). Not pictured are Eva (Eastern Blot) and Chris Condayan, the ASM public outreach manager who later interviewed and filmed us for a feature on science blogging. For some reason (either out of creativity or alcohol consumption) Chris filmed me while having me stand in a phone booth. He's going to edit the interviews into something short and interesting and I'll post a link when it is available (assuming it isn't too embarrassing).

Highlights of ASM 2007 -- May 22

There were many shorter (30 min) talks today, so I'll focus on a few that I found most interesting. Janet Siefert gave a interesting talk on her studies of the "living stomatolites" (large cyanobacterial colonies) of the Mexican desert and how they and associated organisms live under such phosphorous-limiting conditions. Particularly interesting was her discovery of a new species of Bacillus that had many apparent cyanobacterial-derived genes. Janet was replacing Ken Nealson (who couldn't attend for health reasons). I had been hoping to meet Ken as one of the many hats he wears is head of the environmental microbiology division of the JCVI, meaning that he's technically been my boss since mid April. Oh well.

Susan Glasauer talked about her work in studying the biodiversity of metal-reducing bacteria in the Jura mountains of Switzerland. There's more growing there than wine grapes (although the same iron-rich soil that makes for such good wine country is also partly responsible for the microbial diversity)

And to finish off the day, the father of bacterial and archaeal (no, I won't say the "p" word) biodiversity studies, Norm Pace himself, gave an special award lecture as he had been chosen for this year's Abbot-ASM Lifetime Achievement Award. While he made his usual arguments against the use of the word "prokaryote" (which I fully agree with in theory, if not entirely in practice), I found it interesting that he now considers the rRNA tree to represent the nuclear lineage (shades of Jim Lake) rather than the organismal tree.

Highlights of ASM 2007 -- May 21

Monday's talks were all by well-known speakers and were pretty much overviews of topics rather than presentations of any new findings.

Gerry Wright gave an interesting talk on antibiotic resistance. He brought up the points that 1) according to molecular evolution half of all known antibiotics predate the Cambrian explosion and 2) environmental isolates that have never seen a clinical antibiotic quite often have genes for resistance. To understand the development of resistance, we have to stop thinking that the world revolves around humans; we've really stepped into a war between microbes that's been going on long before humans existed.

Ed Delong (one of my heroes) talked about the importance of oxygen-producing bacteria in the oceans and how people tend to forget about their existence and importance, despite these "prokaryotic forests of the sea" producing 50% of the atmospheric oxygen.

And E.O. Wilson (of ants and sociobiology fame) gave a keynote lecture on biodiversity, probably on the basis of his quip made some years ago that if he were a young scientist today, he would become a microbial ecologist rather than an entomologist. It was interesting to hear him talk, as I've heard his rivals Gould and Lewontin speak before, but clearly Wilson's talk was simply a recycled biodiversity of animals talk with a few slides about microbes added -- although I rather liked the (to the general public anyway) more famous Wilson talking about the importance of the work of Woese.

Pictured is the main hall of Union Station -- Toronto's version of New York's Grand Central Station.

In Toronto for ASM 2007

This year the big meeting for the American Society for Microbiology is in Toronto. Which is odd, because Canada has its own professional association, the Canadian Society of Microbiologists. Are they going to hold their meeting in New York? Anyway, I'm here and enjoying a return to a city that I visited several times as a teenager and then as a postdoc in the (relatively) close University of Waterloo. I'll try to post highlights as I see them from the conference each day until Friday.

Oh, I have to tell you an amusing story that occurred when I was going through customs today as I was entering Canada: The customs official asked me why I was entering Canada and I told him that I was attending the microbiology meeting, and he asked me where I worked and I told him I worked at the J. Craig Venter Institute, and he responded with "You know, are they ever going to do studies of the ocean bacteria that live too deep for photosynthesis?". Which is a totally valid question -- the Global Ocean Survey used samples collected from Craig's yacht, not a research vessel, so the samples were from the surface. But I was a bit stunned hearing it coming from a customs official!

Concerning the pictures -- one is of Dundas Square -- which didn't even exist the last time I was in Toronto, and the other is of the so-called World's Biggest Bookstore. I went there today for old-times sake. It is quite a large bookstore, and I was blown away by it when I first visited it in the 1980s, when my idea of a bookstore was a typical Waldenbooks or B. Dalton's. But while it's still larger than than the average Barnes and Noble (or Chapters or Indigo, eh?) location of today, it isn't mindbogglingly larger.

Erdös numbers & other geekery

RPM over at Evolgen has recently posted on the (perhaps facetious) need for a version of an Erdös number in biology. If you don't know what an Erdös number is, it basically is the geekier version of "six degrees of Kevin Bacon". Paul Erdös (1913-1996) was a prolific mathematician who had many co-authors. If you co-authored a paper with Erdös, you have an Erdös number of 1, if you didn't collaborate with Erdös himself but instead with one of his collaborators, you have an Erdös number of 2, and so forth. It's a point of pride among mathematicians to have a low Erdös number.

Well, shouldn't biologists join in on the fun? RPM has suggested that Richard Gibbs should be our Erdös. Of course, he's honest enough to mention that he has a Gibbs number of one, but Gibbs isn't actually a bad choice, at least in genomics. I suggested Craig Venter or Claire Fraser (as I have a both a Venter and a Fraser number of 1), but RPM suggested that I wasn't really getting into the spirit of things. Still, (as you'll see), these connections still help me.

So first of all, having done a postdoc in a Computer Science department, I'd just like to state that I have a respectable Erdös number of 4. (Paul Erdös -> Charles Colbourn -> Derek Corneil -> Paul Kearney -> me).

My Gibbs number isn't so bad either, at 2. (Richard Gibbs -> Craig Venter -> me)

Someone on evolgen suggested Eric Lander. My Lander number is 3 (Eric Lander -> Michael Eisen -> Steven Salzberg -> me).

JCVI Evolutionary Genomics Journal Club on Liu-Ochman

This week I was the presenter for our "Evolutionary Genomics" journal club at JCVI and I chose to present the Liu-Ochman paper on the the stepwise formation of the bacterial flagellum and its reception (part two, three) in the blogosphere. The basic claim of the article is that the 24 core proteins are homologous to each other and this explains how the flagellum evolved through repeated gene duplication events.

Nick Matzke doesn't buy the argument for several reasons: 1) It doesn't seem to be congruent with previous studies 2) At least two of the structures of the presumed homologous proteins don't "look" homologous. and 3) The authors seem to be using the Bl2Seq tool incorrectly. It's odd that Nick focuses so much effort on points 1) and 2) because it is really 3) that is the issue. Personally, I've never been convinced that protein structure is of much use in inferring homology or the lack of it; systematists have been burned so many times by incorrectly assumed (non)homology of gross morphological traits in light of convergent and divergent evolution; why should morphology at the protein level be any different? The beauty of molecular systematics is that it's freed us from having to deal with morphology at all.

At the journal club, we were split on the value of structure for inferring homology, but we all agreed that eyeballing structures, particularly structures that seem to have drawn with different programs and rotated differently. was not a very convincing argument.

We were much more convinced, however, by Nick's demonstration that the authors seem to have performed their BLAST matches incorrectly. As Nick showed, the authors did not have sequence filters enabled, which means that matches to low-complexity regions can artificially inflate BLAST significance, and perhaps more damning, the authors used multiple pairwise BL2Seq runs without correcting for the true size of the search space. And these weren't just assumed to be the problem; Nick demonstrated on a subset of the data that using the correct parameters caused several "significant" BLAST matches to disappear.

This was the introduction to scientific blogging for many of the attendees of the journal club, and they also had some interesting comments about the phenomenon after preparing for the club.

1) While the paper was much mentioned in scientific blogs, generally the mentions were just "Nick Matzke has shown that the Liu-Ochman paper is flawed; here's the link", and not independent analyses of the paper. Yes, this is true of blogs in general, not just scientific ones. But this sort of laziness is very common in traditional media too. Take a look at your newspaper and see how many articles are from news services like AP or Reuters rather than being independent reporting.

2) Why did discussion suddenly fall off after Nick's articles? Does the blogosphere really have such a short attention span?

3) Why haven't we seen a response from Liu and Ochman? Are they not aware of the discussion, or do they simply see criticism on blogs as not being worth responding to?

Wiley and fair use of published figures by bloggers

This has been all over the blogosphere -- even on boingboing (which means that it's probably going to show up on Slashdot in a day or two), but it ties in with what I just posted, and it reminds us of yet another problem with non open access publishing.

Basically, the story is that a PhD student blogger, Shelley Batts, wrote a blog posting about a much discussed recent article that claimed that antioxidants in berries are increased by alcohol (the "daiquiris are good for you" paper). As part of her blog entry, Shelly posted graphs and a table from the paper, as would seem reasonable fair use in discussion of the science. But Wiley Publishing didn't see it that way -- here's their take:

"The above article contains copyrighted material in the form of a table and graphs taken from a recently published paper in the Journal of the Science of Food and Agriculture. If these figures are not removed immediately, lawyers from John Wiley & Sons will contact you with further action."

The only good thing I see about this is that the news has gotten out about what unreasonable asses Wiley are being and hopefully people will think twice before submitting a paper to a Wiley published journal.

BTW, the Wiley E. Coyote image I'm using is supposedly fair use (it's from Wikipedia), but I'll let you know if Warner decides to threaten me over that.

UPDATE: At 1:02 pm, the legal threat against Shelly was retracted:

"There has been a misunderstanding with this issue, inadvertently caused by a junior staff member at our Society. Our official response is below: 'We apologise for any misunderstanding. In this situation the publisher would typically grant permission on request in order to ensure that figures and extracts are properly credited. We do not think there is any need to pursue this matter further.'"

Still, it is disturbing that the concept of "fair use" doesn't seem to be acknowledged in that response -- under fair use, there would be no need for any permission to be asked for in the first place.

Prototaxites a fungus? Who can tell without Open Access?

Prototaxites is believed to have been the largest land organism in the Devonian period, leaving behind tree-trunk sized fossils that have stumped geologists for the 150 years since their discovery. What exactly was it? Traditionally, it was assumed to be an ancient brown algae, largely from analogy with modern giant aquatic brown algae. However, according to a recent news article Francis Hueber and colleagues have just published a paper that gives convincing evidence that it was in fact a giant fungus. An interesting idea -- but unless your institution subscribes to the journal "Geology", you can't read the actual paper to decide for yourself. It's particularly sad that this is the case because the journal isn't published by a commercial company that would be expected to put profit before science, but by a non-profit society that supposedly stands for "Fostering the human quest for understanding Earth, planets, and life". Limiting access to papers seems to be in direct conflict with their stated mission.

RIP Kurt Vonnegut (1922 - 2007)

Well, besides TIGR, Kurt Vonnegut died yesterday as well. So it goes. While many of his later works were rather derivative, one is reminded of the quip about Bob Dylan: "sure, he's derivative nowadays, but the person he's plagiarizing from is his younger self." Certainly both Slaughterhouse Five and Cat's Cradle will stand the test of time, and I'm rather fond of Player Piano and Galapagos as well.

RIP TIGR (1992-2007)

Well, it's official -- TIGR is no more. We had an "all hands meeting" today and Craig informed us that the TIGR name has been officially retired (as has that of the lesser known TCAG, or The Center for the Advancement of Genomics, which had been the "traditional" J, Craig Venter Institute). We are all now employees of the J. Craig Venter Institute. Even our e-mail will be at jcvi.org and not tigr.org. Personally, I don't understand the rationale behind Craig's reasoning -- TIGR means something to the scientific community, and with the possible exception of the recent Global Ocean Survey, the J. Craig Venter Institute is an unknown quantity. But hey, what do I know? In other news, the much rumored "flat organization" that would bring faculty and staff scientists to equality turned out to be just that -- a rumor. I had mixed feelings about that one, anyway. As a staff scientist, I of course would like to move up in the social scale, but I realize that many faculty would be alienated by such a move. TIGR (er, the JCVI) is hemorrhaging enough faculty as it is.

Stacey Singer's "Plasmid"

Last night I when was talking to my brother on the telephone, he mentioned that Stacey Singer, whom we went to high school with, had become a science journalist for the Palm Beach Post and had started a blog, Plasmid. It's a bit anemic at the present (I suppose Stacey's mostly writing actual newspaper articles), but hey, I know someone who grew up to be a science journalist. I guess when I make a major discovery I can call her up to tell her.

You will be showered with good luch

Today I received a disturbing fortune in a fortune cookie at the vaguely Pan-Asian restaurant across from TIGR. Normally, I'm annoyed by "fortunes" that are merely statements like "You have a good heart". Well, today, I received one with a concrete prediction, but a rather distressing one -- "You will be showered with good luch." What's "luch", you ask? Apparently it refers to a series of Soviet satellites. Also, it could refer to a brand of watches made in Minsk (the Communists loved to name their consumer goods after satellites; cf. the East German Trabant). The watch might hurt less.

Back to the Future

Have you ever come across an old e-mail file? I recently was looking at some of my old files and discovered an archive of all of my grad school e-mails from 1992-1998. It's rather eerie to have the ability to look and see what you were doing ten years ago. (Okay, so the movie is about going back 30 years, but hey, cut me some slack). Anyway, bizarrely enough, on April 2nd and 3rd, 1997, I was arguing about gene annotation in Archaeoglobus fulgidus with people who worked at TIGR. Now I work at TIGR. (Well, technically, I now work at the J. Craig Venter Institute, TIGR subdivision -- it's like Hong Kong -- One nation two systems, or something like that).

Talk finished!

This past week I've been freaking out about an internal promotion talk here at TIGR and finally it's over. It went well, I think. Some people have asked me for the slides, and so I've provided links to them in their original Apple Keynote format and as a PDF.

Classic biology books online

I've always had an interest in the history of science, particularly of evolutionary biology, and enjoy reading classic works in the field. While I'm lucky that I live near the Library of Congress, with its fabled collection, it's nice to be able to read from the comfort of my own home (the LoC is non-lending). What to do? One possibility is to read online books. Everybody probably knows that the works of Darwin, Huxley, and other Victorians are available on the net, but you may not know that even early 20th century classics are now available, thanks to the digitizing efforts that have been going on in various university libraries. Some may dislike the idea of reading on-screen, but there are services like CafePress and Lulu that will print and bind a PDF file for you for a small fee (and eventually, we will have practical e-ink devices that will make printing unnecessary. Oh, and flying cars and personal robots too).

Anyway, here are a few significant books that I've discovered on-line:

Hugo de Vries' Species and Varieties, Their Origin by Mutation (1905) -- The classic "saltationist" work by one of the rediscoverers of Mendel's laws, this is a good example of early thought by geneticists on the issue of evolution -- de Vries considered mutation, rather than selection to be the primary force behind evolution.

Thomas Hunt Morgan's The Physical Basis of Heredity (1919) -- The book that established the gene as a real entity on a chromosome rather than an ideal "factor".

R.A, Fisher's The Genetical Theory of Natural Selection (1930) -- Considered the most important advance in evolutionary theory since Darwin, this book ended the "eclipse of Darwinism" caused by people like de Vries by explaining selection in terms of Mendelian genetics.

Self censorship or just common sense?

In today's Nature there's another installment of Prospect by Paul Smaglik (yes, it's not open access -- unclean! unclean!). If you don't read it, Prospect is a column geared towards postdocs and other beginning researchers and aims to give them career advice, often verging on the banally obvious. Today's was a little different -- it's entitled "Could blogs replace résumés?" and suggests that "perhaps it's best to treat your blog as a public document that you wouldn't mind your next boss reading". Well, I suppose -- realizing that what you say on the Internet can come back to haunt you is not new and dates back to the early days of Usenet newsgroups, but at the same time it isn't possible to say anything interesting without potentially pissing off somebody.

The J. Craig Venter Institute's Global Ocean Sampling Expedition

Well, today a series of papers on the Global Ocean Sampling Expedition (including one first-authored by my drinking buddy Rekha Seshadri and another by my former mentor Jonathan Eisen) were published in PLoS Biology. We also had an institute wide (TIGR is now part of the J. Craig Venter Institute, if you hadn't heard) happy hour to celebrate the event. I may be a fan of "free as in free speech, not as in free beer" software, but I'm not one to turn up my nose at literal free beer (which was provided). And the papers themselves are actually rather interesting. While there's currently a tension between TIGR (run by Craig's ex-wife Claire Fraser, and run rather like a university minus the teaching) and the rest of the Venter Institute (more centrally controlled by Craig), you have to admit that good science can be done in Craig's domain.