Friday, April 29, 2005

Nee Darwinist.

I though the following quotes from the Nature cover story on ID were appropriate given my current blogger profile (on the top right hand side of this page):
Darwinists are divided in their response to the idea's growing profile on campus . . .

Darwinist Eugenie Scott rejects intelligent design on scientific grounds whereas Lutheran George Murphy (above) rejects it for theological reasons.

[Eugenie] Scott, who is perhaps the nation's most high-profile Darwinist, is frustrated by the scientific community's inability to grapple with the issue.
The emphases are all mine.

For those of you too lazy to read my profile, I reproduced it below:
I am a geneticist. I am an evolutionary biologist. I am not a Darwinist. Anyone who claims to be a Darwinist or alleges that someone else is a Darwinist does not understand evolutionary theory.
Pharyngula has already addressed the flaws in this article, so I won't say any more.


PZ Myers has another excellent post, this time on the role of temperature in regulating development. This got me to thinking about a few things:
  1. Developmental plasticity probably makes for great difficulties in comparing experimental results obtained by different labs, different experimenters in the same lab, or even the same experimenter at different times. I bet this causes problems when comparing gene expression data obtained in different experiments (yes, I know there are internal controls for microarrays/rtPCR).
  2. More practically, rearing temperature can affect the penetrance of certain Drosophila mutants. For example, the mutation eyeless (ey) causes the eyes to appear much smaller than usual (similar phenotype as Drop). When mutant flies are reared at higher temperatures they have nearly wild-type eyes. This is a drastic phenotypic difference! I learned this while TAing a biology course in which this mutation was used as a phenotypic marker. In order to ensure that the students had enough flies to score every two weeks they were reared at above 25C. This changed the penetrance of the mutant phenotype and gave the students fits scoring their crosses.
  3. Phenotypic plasticity also plays a role in evolution. This is most famously described in West-Eberhard's Developmental Plasticity and Evolution. It also provides for a nice way in which the genotype can "interact" with the environment. Because temperature influences the phenotypic expression of alleles, a genotype may manifest itself differently in different environments. I'm sure this is nothing new, but it provides a more tangible way to understand why fitness depends on the environment.
Go read PZ's post for yourself, as it's another great example of his ability to distill a scientific publication for lay consumption.

Monday, April 25, 2005

Guns don't kill people . . .

Check out this gem of a quote from Tom Delay:
Guns have little or nothing to do with juvenile violence. The causes of youth violence are working parents who put their kids into daycare, the teaching of evolution in the schools, and working mothers who take birth control pills.
Guns don't kill people, Darwin and Ortho TriCyclin Do.

Friday, April 22, 2005

In this week's Nature.

I was going to post on 2 short news features in Nature this week. PZ Myers beat me to one, but I don't know if anyone has talked about the second.

Ever wonder if anyone reads your abstract that you submit for a meeting if there are an unlimited number of spots? Well, some crafty computer scientists at MIT decided to find out. The wrote a computer program to generate a scientific article and submitted it for presentation at a professional meeting.

Most graduate students would be delighted to have a paper accepted for presentation at an international scientific conference. But Jeremy Stribling, a computer-science graduate at the Massachusetts Institute of Technology (MIT) in Cambridge, wasn't sure whether to be amused or alarmed.

His paper, "Rooter: a methodology for the typical unification of access points and redundancy", co-authored with Daniel Aguayo and Maxwell Krohn, was accepted for the 9th World Multi-Conference on Systemics, Cybernetics and Informatics (WMSCI), to be held in Florida, in July. But Stribling didn't write it; he let a computer do it.

Stribling and his colleagues have developed an 'automatic computer-science paper generator' that cobbles together articles adorned with randomly generated graphs. The 'results' are totally spurious.

The MIT researchers say they hoped to cause "maximum amusement" by aping the jargon of the less illustrious papers in computer science. But they also had a more serious goal: to test whether such meaningless manuscripts could pass the screening procedure for conferences that, they feel, exist simply to make money.

'Rooter' passed the test: the WMSCI accepted it, albeit without peer review. The paper claims, among other things, that "the famous ubiquitous algorithm for the exploration of robots by Sato et al. runs in Omega((n+log n)) time".

The name of that conference has some serious jargonization! I don't know how abstracts were reviewed for this conference, but from my experience it's typical to either submit your paper as either a talk or poster presentation. Abstracts that are submitted as posters for meetings that I attend always get accepted, and I honestly don't know if they get reviewed. Basically, if you want to present a poster at a meeting, you can present a poster. I don't know if this is different in other fields.

For most of the meetings I attend, abstracts submitted for talks go through a review process in which only the best ones are presented orally. The remaining submissions are relegated to posters. I assume that only the abstracts submitted for consideration as talks get critically reviewed. As you can see, it's quite easy to present at the meetings I want to go to if you just want to present a poster.

I don't typically attend meetings that are put on just to make money. There isn't enough money in my field for people to take advantage of us! Maybe if I worked in cancer research (where there is loads and loads of money thrown around) I would be tempted to spend some of it on shitty meetings. Currently, though, I never spend more than $100 to register for a meeting (grad student discounts are nice) and that money goes toward putting on the meeting. I can hardly see the meetings I attend as money making scams -- usually they scrape by with just enough money to put the meeting on.

Thursday, April 21, 2005

Bead Based Resequencing.

I had a busy day attending seminars yesterday. I already wrote about Phil Skell at our evolutionary genetics seminar. Later in the day, I went to a genomics/bioinformatics seminar on a new sequencing technique. The company (454) has developed a new method that they hope will complement the shotgun sequencing approach. I describe the method below (along with some background on shotgun sequencing) and its potential applications for polymorphism studies.

Shotgun sequencing is the dominant method for genome sequencing in the post-genomic world. The approach, in a nutshell, involves sequencing random fragments of the genome, then assembling those fragments based on sequence overlaps and mate-pair information. You can learn much more about the method here. The shotgun method has benefits in that you do not need to know much about the genetics of the organism whose genome you plan to sequence (of course, the more you know, the easier the process). The main drawback of the method, however, is that it is extremely labor intensive (involving many intermediate steps) and costs an arm and a leg to sequence a eukaryotic genome with good coverage. The quality of a genome sequencing project is defined by how much "coverage" we have of the entire genome. The modern standard is 6-10x coverage. This means that, on average, each nucleotide is sequenced 6-10 times. The higher the coverage, the more confident we are in our nucleotide calls and the higher the probability we have sequenced a majority of the genome. There are diminishing returns to increasing coverage because you end up sequencing the same nucleotides without getting at those hard to sequence regions. This is why 6-10x coverage is considered the ideal (a balance between high coverage without diminishing returns).

Resequencing projects aim to sequence a portion of the genome or a bunch of loci arrayed throughout the genome in multiple individuals of an organism with a completely sequenced genome. The sequences are then assembled onto the backbone of the completely sequenced reference genome. The common method is PCR based and similar in technique to shotgun method, but different in that it is a targeted process. These studies can give important insights into the function of genes and the evolution of genes and populations.

The new method that I heard about yesterday will allow for whole genome resequencing (as well as targeted resequencing) with much more coverage and for a lower cost. For the cost of resequencing in the classical method with 0.5x coverage, this method can resequence at ~30x in much less time. Yes, I know I sound like an infomercial for 454 (the company behind this technique), but I was pretty impressed and my statements are not influenced by gifts from the company.

The method works by affixing ~1kb ssDNA to tiny beads. The DNA is then replicated, and the replicated strands are also affixed to the beads. They then replicate the DNA using nucleotides that emit a pyrophosphate when added to the growing DNA strand. These pyrophosphates can be detected using the method described here. Basically, they can "watch" the DNA strand replicate in real time and record which nucleotide is being added. They then record the order in which nucleotides are added to the chain, and that's the sequence of that fragment.

Presently, the method is good for sequencing 100-200 base pairs (PCR based approaches sequence 700-800bp). Even though they are sequencing smaller fragments, the method is capable of generating more coverage because they sequence many more of those fragments than under the traditional shotgun approach. One major limitation of the method, though, is that it is unable to sequence mononucleotide repeats (e.g., AAAA or GGGG) because all of the nucleotides get added at the same time in the sequencing reaction. Also, because the sequenced fragments are small and there is no mate pair information, the sequences assemble into smaller contigs/scaffolds than under the traditional shotgun approach. This is not a major issue for resequencing projects because the sequences can be assembled on top of the whole genome sequence. If they want their bead based method to be used for de novo sequencing, they must improve sequencing over mononucleotide repeats and increase the size of the sequence reads.

Despite its limitations, this method could be a welcome advance for researchers interested in resequencing. For instance, if I want to describe patterns of nucleotide variation in my species of interest with a sequenced genome, I could chose a bunch of loci and perform targeted sequencing at about 2x coverage in a bunch of individuals. Using this new method, I could get more coverage at my loci of interest in less time, or perform a whole genome resequencing project in multiple individuals with impressive coverage and not have to worry about choosing loci because I would be sequencing the entire genome. At this point in time, the method has been tested on bacterial genomes (~10 megabases in length), but they plan to extend it to eukaryotic genomes (about 1000 times larger). If it's cheaper, faster, and better (more coverage) this may be the wave of the future in DNA sequencing.

Wednesday, April 20, 2005

An Appeal to Authority.

Phil Skell, an emeritus Professor of Chemistry (and a National Academy member) from my university, decided to grace our weekly Evolutionary Genetics seminar today. For those of you unfamiliar with Skell, read what PZ Myers has to say about him. The talk was on a new method for determining orthologs for phylogenetic construction (don't worry if I just over-jargoned you, it's not all that important). The point is, the presenter was constructing evolutionary trees.

Dr. Skell's appearance was not new (he showed up nearly every week for an entire semester once), but he hasn't been coming by recently. He never used to ask questions -- he'd just sit attentively not giving any indication whether he disagreed with the material or not. Skell is an interesting character, in that he is not an ardent creationist, just a religious Christian who has issues with evolutionary biology (and it's never quite clear what those issues are).

At the end of the talk, Dr. Skell asked a vague question about reconstructing ancestral states. The grad student who was presenting answered the question correctly, saying that she does not study ancestral reconstruction, she is not the appropriate person to answer the question, but it is an active area of research.

Skell then shifted into "odd-ball mode" and began talking about a seminar he had seen by Nobel Laureate, Eli Wiesel. Wiesel spoke about finding lost religious documents, and that such information may be found in our DNA (either Wiesel knows nothing about genetics or Skell misrepresented Wiesel). He asked the speaker at today's seminar what she thought about this, and I can't remember her answer because I was focusing all of my attention on suppressing my laughter and frustration with Skell. I believe she gave the same answer as above (ancestral reconstruction is not her field) and paid far too much respect to the question than it rightfully deserved.

Skell's tangent from his tangent (the original question on ancestral reconstruction was off-topic to begin with) was the classic logical fallacy of appealing to authority. It is oftentimes used by those people ignorant of the topic they are discussing to make themselves appear knowledgeable by citing some respected source. Ironically, Skell's appeal made him look completely ignorant as Wiesel is not an authority on genetics (let alone evolutionary genetics). It would do right for those "scientists" who wish to criticize (or even comment on) evolutionary research to familiarize themselves with the material to the point where they can ask coherent questions and understand the major issues.

Friday, April 15, 2005

The joys of advanced education.

I think this comic pretty much sums it up:

Wednesday, April 13, 2005

My own little hell.

I just got back from the library where I checked out a book entitled Discrete Multivariate Analysis: Theory and Practice -- I'm hoping it's more practice and less theory. When I asked the librarian whether I was allowed to check it out, she replied, "Yes, but why would you want to?"

I do not know what "discrete multivariate analysis" is, and I have had very little training in mathematics (some calculus, some statistics, and some other stuff I picked up along the way). There is no chance in hell that I'm going to understand all of the material in this book. I'm hoping the little bit I need is somewhat clear to me after reading it over twenty to thirty times.

If the material is totally out of my ballpark, why would I ever want to check out this book? It all started with these papers published over fifty years ago. I began reanalyzing their results, and that led me to this paper on fitness and recombination. I am now trying to apply a statistical test developed in that paper to a more complex scenario. To do so, I need to figure out how a value in that paper was derived so that I can derive it for my example. That's where the book with the scary name comes in.

Last time I checked, I'm working on a degree in Genetics. I never thought I'd be getting books from the library on mathematical concepts I didn't even know existed when I signed up for this gig. I guess no scientific discipline exists in isolation, and in order to study biology in this modern world you need to have a good handle on the life sciences as well as math, physics, chemistry, and anything else that may intersect your path.

Wednesday, April 06, 2005

Unintelligent Design.

More on the Intelligent Design legislation in Pennsylvania:

1. Read about it here, here, and here.

2. I'm considering organizing an effort in my department to send a letter to both the subcommittee and our representative (who happens to be an author on the bill). If anyone has any suggestions, please post a comment.

Considering our department's excellent reputation in evolutionary genetics, I'm hoping that a letter from both the faculty and grad students should carry some weight. I would like to have a draft posted soon so that people can offer comments.

Tuesday, April 05, 2005

I come back to PA and this is what I find.

I got back from a meeting in California a couple of days ago, and I'm still trying to deal with the new time zone and the daylight savings time change. Upon checking some websites, I discovered the following legislation is proposed for PA:
Section 1. The act of act of March 10, 1949 (P.L.30, No.14), known as the Public School Code of 1949, is amended by adding a section to read:

Section 1516.2. Teaching Theories on the Origin of Man and Earth.--(a) In any public school instruction concerning the theories of the origin of man and the earth which includes the theory commonly known as evolution, a board of school directors may include, as a portion of such instruction, the theory of intelligent design. Upon approval of the board of school directors, any teacher may use supporting evidence deemed necessary for instruction on the theory of intelligent design.

Hopefully we can mobilize our department and prevent the stupification of PA.