It’s my birthday, and I’ll grade exams if I want to Grade exams if I want to, grade exams if I want to You would grade exams too if you had this much work to do
November 2005 Archives
Last weekend I attended a bioinformatics conference at the North Avenue Trade School for Wayward Boys. I got to finally meet my postdoctoral advisor, Jeff Thorne, and got a copy of the journal my Dawg paper is published in. The full reference to the paper is:
Cartwright, R.A. (2005) DNA Assembly With Gaps (Dawg): Simulating Sequence Evolution. Bioinformatics 21 (Suppl. 3): iii31-iii38.
DNA assembly with gaps (Dawg): simulating sequence evolution Reed A. Cartwright
Department of Genetics, University of Georgia Athens, GA 30602-7223, USA
Motivation: Relationships amongst taxa are inferred from biological data using phylogenetic methods and procedures. Very few known phylogenies exist against which to test the accuracy of our inferences. Therefore, in the absence of biological data, simulated data must be used to test the accuracy of methods which produce these inferences. Researchers have limited or non-existent options for simulations useful for studying the impact of insertions, deletions, and alignments on phylogenetic accuracy.
Results: To satisfy this gap I have developed a new algorithm of indel formation and incorporated it into a new, flexible, and portable application for sequence simulation. The application, called Dawg, simulates phylogenetic evolution of DNA sequences in continuous time using the robust general time reversible model with gamma and invariant rate heterogeneity and a novel length-dependent model of indel formation. On completion, Dawg produces the true alignment of the simulated sequences. Unlike other applications, Dawg allows indel lengths to be explicitly distributed via a biologically realistic power law. Many options are available to allow users to customize their simulations and results. Because simulating with indels would be problematic if biologically realistic parameters could not be estimated, a script is provided with Dawg that can estimate the parameters of indel formation from sequence data. Dawg was applied to the sequences of four chloroplast trnK introns. It was used to parametrically bootstrap an estimation of the rate of indel formation for the phylogeny. Because Dawg can assist in parametric bootstrapping of sequence data it is useful beyond phylogenetics, such as studying alignment algorithms or parameters of molecular evolution.
Availability: Dawg 1.0.0 can be obtained at the following websites: http://www.genetics.uga.edu/sw/ or http://scit.us/dawg/. The package includes source code, example files, a brief manual and helper scripts. Binary distributions are available for Windows and Macintosh OS X. A development page for Dawg exists at http://scit.us/dawg/, with links to a Subversion repository, mailing lists and updated versions.
I learned today that I was awarded UGA’s James L. Carmon Scholarship for Computational Research for my work on Dawg. (I share the award with a student in Physics and Astronomy. I’m not sure what he does.) The scholarship is $4000, which is very good money especially with Christmas and birthdays coming up.
We caught a student cheating on an exam today. He was copying from his notes.
There was no need to cheat on this exam. The questions were taken directly from the review questions posted by the professor on WebCT. We even answered every question during discussion sections.
The student was very apologetic when confronted and tried to explain his actions. He had other tests. He was premed. I told him I didn’t care. After the test he came down to apologize to me, and I told him not to apologize to me, but to his parents and the other people who had invested in his education.
Our professors are away right now. We’ll see what they have to say next week.
Now I find out that we skipped a week and I won’t be presenting until next Monday.
Here’s the first part of the presentation. I removed the second part which contains massive amounts of unpublished data. Isn’t Beamer+PDFLaTeX cool!
Last March, Susan Lolle and colleagues reported in Nature about a high reversion rate in a particular Arabidopsis mutant, HOTHEAD (HTH) (Lolle SJ et al. 2005). This paper is notable because it hypothesized that the cause of the reversion was due non-Mendelian inheritance of an RNA cache. The media jumped on this paper and promoted it as if Lolle and colleagues had demonstrated the existence of non-Mendelian inheritance. They hadn’t; they only proposed a non-Mendelian inheritance to explain their data. Many of the scientists that I have spoken to did not like their hypothesis.
In the latest Plant Cell, Luca Comai and I have published a paper detailing an alternative hypothesis for the observations of Lolle and colleagues. This hypothesis is more attractive than the one proposed by Lolle and colleagues because it relies on the already established mechanisms of mutation and selection. This hypothesis also relies on knowledge about the structure of the HTH gene product, which is information not considered in the Nature paper.
My regular readers may remember that last March, right after the Nature paper came out, I discussed it on my blog (here and here). Those of you that remember the discussion will be familiar with our hypothesis already since I blogged it back then. That’s correct; this paper derived from a blog post that I did. Blogging does pay off.
Before I detail the paper, a little more background is in order.
Luca Comai is a Professor of Biology at the University of Washington. Soon after the Lolle et al.’s paper came out, he was asked to cover it in a journal club with grad students. From that discussion he came up with an alternative hypothesis to explain the data presented in the paper. He shared his hypothesis with colleague Steve “Number 22” Henikoff at the Fred Hutchinson Cancer Research Center, who also took an interest in the hypothesis. Luca submitted his hypothesis to Plant Cell, and it went through several rounds of review but was eventually accepted for publication. However, the slow progress of Luca’s paper was impacting Steve who was trying to publish an elaboration of Comai’s hypothesis, but was unable to cite Luca’s yet-to-be published hypothesis.
So in early September, Steve googled the RNA Cache hypothesis and discovered my blog sitting on the first page and upon reading my blog he realized that I had totally scooped Luca. Given the slow progress of the people at Plant Cell, Steve considered citing my blog for the toxic-mutator hypothesis. However, on September 6th, I got a surprising email:
A friend of mine just brought to my attention your blog on hothead. I have developed an explanation for the described phenomenon that is nearly identical to the one you posted in March in your blog. In April I submitted it to Nature, which promptly rejected it. Soon after I submitted to the Plant Cell where it has undergone considerable criticism (and skepticism). After three review cycles, it has been accepted. I enclose the latest version, which is not too far from the original one. I was not aware of your contribution until today. I copy Nan Eckhardt, the editor of the Plant Cell in charge of this commentary so that we can hear her opinion on this matter. I think that I should acknowledge your work in some way. One way would for you to be a coauthor. The other would be for me to quote your blog. Just in case you have not dealt with this matter recently, I should clarify that our religion (I call it the toxic mutator hypothesis) has very few acolytes. So, I do not know whether I am inviting you to step up on the chariot, or on the railroad tie. Read the commentary at your convenience and let me know what you think.
Regards, Luca Comai
So needless to say, as a graduate student looking to increase a C.V., I jumped at Luca’s charitable offer for a coauthorship, especially on an already accepted paper. There are maybe three sentences in the published paper that I had anything to do with, but I did produce the same hypothesis as Luca and scooped him to boot. I never really expected that my blog would lead to any publications.
Now in our paper, Luca and I propose that null mutations in the hothead gene may result in the accumulation of a toxic mutator that leads to an increased mutation rate across the entire genome (Comai and Cartwright 2005). We point out that in a previous paper HTH was shown to be related to a group of enzymes responsible for breaking down aromatic compounds (Krolikowski et al. 2003). (Many aromatic compounds have been shown to cause mutations.) Furthermore, we argue that selection during pollen competition for hth revertants may explain the large number of revertants. There’s more to it than that, but I’ve kept it simple for this blog. You can check out the paper for more.
In an invited paper that appears along side ours, Steve beautifully elaborates on this “toxic-mutator” hypothesis in his paper. Steve proposes that the substrate of the hothead gene is a inhibitor of DNA polymerase λ, which is the enzyme that plants use for base excision repair (BER), the major pathway of endogenous DNA damage repair (Henikoff 2005). As Steve says, “an excellent candidate for a toxic mutator is a glycosylated mandelonatrile inhibitor of DNA polymerase λ.” Steve further points out that the inhibition of BER may induce would also explain the gene conversion observations of Lolle et al. because the lack of BER would lead to repair via homologous strand invasion. You can check out his paper for more details.
I think that that the toxic mutator hypothesis is a very promising explanation for the observed phenotypes of hothead mutants, especially given Steve’s elaboration. I’ve been told that the people who originally published the RNA cache hypothesis also like our hypothesis. My involvement would never had happened had I not taken the opportunity to blog about this paper and independently propose the toxic mutator hypothesis. Science blogging does matter, and science blogging does make a difference.
- Comai L and Cartwright RA (2005) A toxic mutator and selection alternative to the non-Mendelian RNA cache hypothesis for hothead reversion. Plant Cell 17:2856-2858.
- Henikoff S (2005) Rapid changes in plant genomes. Plant Cell 17:2852-2855.
- Krolikowski KA et al. (2003) Isolation and characterization of the Arabidopsis organ fusion gene HOTHEAD. Plant J. (4):501-11.
- Lolle SJ et al. (2005) Genome-wide non-mendelian inheritance of extra-genomic information in Arabidopsis. Nature. 434(7032):505-9.
Tiffany mentioned to me today that Texas is voting to ban marriage today. Proposed constitutional amendment #2 reads,
A JOINT RESOLUTION proposing a constitutional amendment providing that marriage in this state consists only of the union of one man and one woman.
BE IT RESOLVED BY THE LEGISLATURE OF THE STATE OF TEXAS:
SECTION 1. Article I, Texas Constitution, is amended by adding Section 32 to read as follows:
Sec. 32. (a) Marriage in this state shall consist only of the union of one man and one woman.
(b) This state or a political subdivision of this state may not create or recognize any legal status identical or similar to marriage.
SECTION 2. This state recognizes that through the designation of guardians, the appointment of agents, and the use of private contracts, persons may adequately and properly appoint guardians and arrange rights relating to hospital visitation, property, and the entitlement to proceeds of life insurance policies without the existence of any legal status identical or similar to marriage.
SECTION 3. This proposed constitutional amendment shall be submitted to the voters at an election to be held November 8, 2005. The ballot shall be printed to permit voting for or against the proposition:
“The constitutional amendment providing that marriage in this state consists only of the union of one man and one woman and prohibiting this state or a political subdivision of this state from creating or recognizing any legal status identical or similar to marriage.”
Someone claiming to be the state attorney general’s office has been calling Texas voters to tell them that “shadowy group” was calling people to warn them about this amendment. The “AG’s” recording said that the amendment is to protect traditional marriage.
The only problem is that as worded the amendment clearly bans Texas governments from recognizing any marriage as well as anything similar to marriage. The “AG” is clearly wrong about what the amendment literally says.
Given that this amendment is being promoted as an anti-homosexual vote, I suspect that it will pass. It will be interesting to see what is going to happen after it passes.
Amazing, I just finished reading a pair of posts about how some Sony CDs now install secret software that prevents you from detecting their copyright protection scheme. Such software is illegal and is poorly written. It can even be used by virus to hide themselves. Go read these two articles and never buy from Sony again.
Rootkit is technology that hides software from the user and security software. This kind of technology is normally used by malware authors that want their presence to remain undetected in the system as long as possible. DRM software is not malicious but it has other reasons for hiding from the user. DRM software restricts the user’s ability to make copies of a record and for that reason uses technology that prevents removal and modification of the software.
EULASony BMG is currently using a rootkit-based DRM system on some CD records sold in USA. As far as we know, this system has been in use since March 2005. We’ve made some test purchases for Sony BMG records from Amazon.com and can confirm that they contained this technology.
The entire experience was frustrating and irritating. Not only had Sony put software on my system that uses techniques commonly used by malware to mask its presence, the software is poorly written and provides no means for uninstall. Worse, most users that stumble across the cloaked files with a RKR scan will cripple their computer if they attempt the obvious step of deleting the cloaked files.
While I believe in the media industry’s right to use copy protection mechanisms to prevent illegal copying, I don’t think that we’ve found the right balance of fair use and copy protection, yet. This is a clear case of Sony taking DRM too far.