Archive for March, 2008
This is already old news, but in this week’s issue of Science, Gibson et al. published their paper on the synthesis of a genome of Mycoplasma genitalium. (Sometimes I just have to wait for a physical copy of the journal to arrive before I have time to read a paper.) This work was performed at the J. Craig Venter Institute (JCVI) in Rockville, Maryland. A special commentary in the Perspectives section, “Reconstruction of the Genomes”, was written by Drew Endy, who is Assistant Professor in the Biological Engineering Department at MIT. (A subscription to Science is required to read the paper and the commentary.)
The paper was originally published online on 24 January 2008, at which time there was a lot of coverage in the press and in blogs. For example, see “Synthetic Genome: Signed, Sealed, Decoded”, by Andrew Pollack of the New York Times, and a roundup of coverage of the announcement at blog.bioethics.net. This paper was also the topic of Science Friday on 25 January 2008.
While the assembly of this synthetic genome is without a doubt a significant technical achievement, the paper does not reveal whether the genome can be transplanted into a bacterial cell. This makes the result anticlimactic; it was like reading about the building of a new airplane, with lots of description about the design of the wings and how the rivets had to be placed just so, but without a demonstration that the airplane could actually fly. I suspect strongly that the transplantation was attempted (several times) without success.
The same group has shown that it is indeed possible to transplant a genome from one bacterial species to another, as described in a paper in Science by Lartigue et al. We must now wait for the JCVI to get their airplane off the ground.
March 05 2008 | Biology | Comments Off
We are on the verge of being able to have our genomes sequenced and analyzed. Today in the article “Gene Map Becomes a Luxury Item”, by Amy Harmon of the New York Times, Ms. Harmon describes how wealthy people are beginning to sign up to have their genomes sequenced and analyzed by Harvard Professor George M. Church’s company Knome at a price starting at $350,000. (Knome is pronounced “know me”, and the company’s web site proclaims “know thyself”, a play on the company’s name.)
University of California—Davis Professor Jonathan A. Eisen, on his The Tree of Life blog, jokingly complained that Ms. Harmon had interviewed him but had discarded his quotes. Ms. Harmon, good sport that she is, responded in the comments by contributing outtakes of the article that included discarded quotes from Dr. Eisen and from J. Craig Venter.
Dr. Venter, of course, has already had his genome sequenced and analyzed by his institute, the J. Craig Venter Institute in Rockville, Maryland. The paper describing Dr. Venter’s genome was published in PLoS Biology. Dr. Venter has written a book, A Life Decoded: My Genome: My Life, and a good review is available on Dr. Jonathan Badger’s T. taxus blog.
Dr. James Watson, one of the co-discoverers of the structure of DNA, has had his genome sequenced; the data are available at the James Watson’s Personal Genome Sequence Browser web site at Cold Spring Harbor Laboratory.
Dr. Church has also organized the Personal Genome Project. This project will sequence and analyze the genomes of volunteers, who will share their medical records, making the data much more useful. I wrote eight days ago about the 1000 Genomes Project, for which medical records will not be available. A blog about the Personal Genome Project, named The Personal Genome, is written by Jason Bobe.
Another company that is providing personal genome data is 23andMe, which provides a blog named The Spittoon. For about $1000, 23andMe obtains data on nearly 600,000 single nucleotide polymorphisms (SNPs) and provides a genetic analysis of the data. Andrew Scheidecker had his genome analyzed by 23andMe in December, 2007, and wrote software called Personal Genome Explorer that made his data available to everyone.
The goal of inexpensively obtaining a genome analysis was deemed important enough for the Archon X Prize for Genomics to promise an award of $10 million for the successful sequencing of 100 genomes in 10 days at a cost of less than $10,000 per genome. See “$10 Million Prize Set Up for Speedy DNA Decoding”, by Nicholas Wade of The New York Times.
Other companies that have developed high-throughput sequencing technologies that might make the relatively inexpensive genome within reach are 454 Life Sciences, Helicos BioSciences, and Pacific Biosciences. Dr. Eisen saw a talk about the Pacific Biosciences technology and came away enthusiastic, writing in his blog:
But it was the last talk of the whole meeting that really did blow my mind. It was from Steve Turner from Pacific Biosciences. He presented an overview of their sequencing technology as well as a tiny bit of data. Now, normally I am uninterested in marketing talks where little data is presented. But this talk was different. First, their technology clearly has enormous potential for revolutionizing the sequencing field. Basically, what they are doing is reading the activity of a DNA polymerase as it replicates a single DNA molecule and they do it in real time. He referred to this as using the DNA polymerase as a sequencing engine and then he took the crowd through the details of the technology and some of the modifications they have made to make it work better.
Ms. Harmon’s article is one of a series in the New York Times named The DNA Age; another good article written by Ms. Harmon is My Genome, Myself: Seeking Clues in DNA. Other good articles at the New York Times on personal genomes and high throughput sequence are “The Race to Read Genomes on a Shoestring, Relatively Speaking” and “Working by Eavesdropping on DNA Doing Its Work”, both by Andrew Pollack.
In a few years, it will be routine for everyone to have their genome sequenced and analyzed. It will take a long time to get the quality of the predictions up to a useful level, however. How much of the genome needs to be sequenced to obtain an accurate analysis, 600,000 SNPs (23andMe) or the full genome (Knome, Personal Genome Project)? I personally am interested in having my genome analyzed because, as a scientist, I am always interested in data. However, I would consider the genetic analysis to be speculative until many more genomes have been analyzed.
Notes added on 6 March 2008:
The Genetic Future blog has a post from 22 January 2008 about negative reaction to 23andMe.
I learned from GenomeWeb today that on 8 February 2008, Helicos BioSciences announced that it had sold its first sequencer. Yesterday, Expression Analysis confirmed that they were the purchaser. Expression Analysis said they will use the sequencer for “de novo sequencing, candidate gene sequencing, and digital gene expression.”
March 04 2008 | Biology | Comments Off
I hope I won’t write too many posts about the mechanics of blogging, but I have spent the entire day studying Cascading Style Sheets: The Definitive Guide, 2nd Edition, by Eric A. Meyer, in an effort to solve some minor infelicities with the WordPress theme I’ve been using.
The theme used for this site is based on Unlimited 1.0, by Sadish Bala. I licensed the Unlimited 1.0 theme for $20 and then began modifying it, mostly by changing the style sheet and providing a new logo image.
Today I discovered that the theme did not handle font-resizing well. For example, a Firefox user on a Mac OS X computer can use command-+ to increase the size of the fonts on a web page. I find that when my eyes get tired, the easiest way to ease them is to enlarge the fonts on the computer screen.
The Unlimited 1.0 theme was designed to use a static width of 900px. When the user enlarges fonts on a static-width page, the structure of the page begins to break down as the browser attempts to render the larger text in an unchanging region. The solution to this problem is to build flexibility into the web page so that when the user enlarges the font, the page is also enlarged to make more room. The way this is done is to specify widths of div elements using em units instead of px units. One em unit corresponds to the height of the letters of the font, so when the size of the font increases, the length of one em also increases, and as a consequence the width of the div element also increases.
I changed the width of the entire page to 70em, with the left column set to 52em total width and the right column to 18em total width. I also fixed minor problems with the menu and footer so that they would resize themselves, too.
If you care to experiment with a standards-compliant browser such as Firefox 2.0 or Safari 3.0, you will see that the web pages for my blog now resize nicely when you make the fonts larger or smaller.
I am also finicky about compliance with XHTML standards, and I discovered that the Links widget provided with WordPress creates multiple li elements with the same ID when you have more than one category in your blogroll. I replaced that widget with the LinkBlock plugin written by M. Holger. The LinkBlock plugin allows you to create up to nine blogroll-style widgets in your sidebar. I needed this because I have a blogroll, a podcast roll, and a website roll. The LinkBlock plugin handles the IDs correctly so that an XHTML validator does not complain.
Everyone knows that there are three generic font families that can be used in CSS, serif, sans-serif, and monospace. What I learned today is that there are two more generic font families, cursive and fantasy. This is what these look like:
font-family: cursive
Lorem ipsum, dolor sit amet, consectetuer adipiscing elit, sed diam nonummy nibh euismod tincidunt ut laoreet dolore magna aliquam erat volutpat. Ut wisi enim ad minim veniam…
font-family: fantasy
Lorem ipsum, dolor sit amet, consectetuer adipiscing elit, sed diam nonummy nibh euismod tincidunt ut laoreet dolore magna aliquam erat volutpat. Ut wisi enim ad minim veniam…
A note: CSS, The Definitive Guide, 3rd Edition, by Eric A. Meyer, was published in November, 2006. My experience with buying O’Reilly books is that as soon as I buy one, a new edition is released one or two months later.
Note added on March 4, 2008:
On my Mac OS X computer, the paragraph styled with the cursive font is displayed using Apple Chancery by both Firefox 2.0.0.12 and Safari 3.0.4. (Apple Chancery is the font I used to create the logo for this site.) The paragraph styled with the fantasy font is displayed using Papyrus.
Under Windows XP, the results are different. Firefox 2.0.0.12 uses Comic Sans MS for cursive and Calibri for fantasy. Internet Explorer 6.0.2900 also uses Comic Sans MS for cursive but Algerian, an all upper-case font, for fantasy.
I expect other variations for browsers under Windows Vista and Linux.
March 03 2008 | Computing | Comments Off
I spent this morning reading Jonathan Badger’s T. taxus blog (“Reflections on science, literature, and history by an American Badger”) and web site. Jonathan is a microbial genomicist at the J. Craig Venter Institute (JCVI) in La Jolla, California. Taxidea taxus is the systematic name for the American badger.
In May, 2007, Jonathan provoked a long and fascinating discussion of a paper by Liu and Ochman on the formation of the flagellar system. The consensus was that the paper was irretrievably flawed because of the incorrect use of and incorrect interpretation of BLAST results.
However, Jonathan made a surprising point that many disagreed with.
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.
Others in the discussion argued forcefully and convincingly that folds are more highly conserved than sequence, and that similar folds provide strong evidence for homology (descent from a common ancestor). I learned a lot from this discussion that will be useful to me.
As I continued my reading, I discovered from Jonathan’s publications page that Jonathan was a coauther on the paper describing the genome sequence of Synechococcus CC9311. The first author was Brian Palenik, a friend of mine who was doing his postdoc in Bob Haselkorn’s lab at the same time I was doing mine. Brian is a much better scientist than I am and deserves his success.
Jonathan’s review of J. Craig Venter’s book, A Life Decoded: My Genome: My Life, piqued my interest, so now I will have to track down a copy.
This was time well spent for me, and I derived great enjoyment in reading Jonathan’s blog. Jonathan hasn’t posted since December, 2007; I am looking forward to new contributions.
March 02 2008 | Biology | Comments Off
On 25 February 2008, Microbe World Radio reported on the 5000 virus genome project, a research project initiated by Professor Marilyn J. Roossinck at the Samuel Roberts Noble Foundation in Ardmore, Oklahoma. Dr. Roossinck’s objective is to use the high-throughput technology from 454 Life Sciences to obtain the sequences of the genomes of 5000 different plant viruses isolated from plants in Costa Rica.
The idea is that plant viruses are poorly understood but play important roles in nature. In the 26 January 2007 issue of Science, Dr. Roossinck and colleagues published a paper in which they described a virus that conferred the ability of a fungus and a tropical grass, in a three-way mutualistic association, to grow at high soil temperatures. When the fungus was cured of the virus, it could no longer confer heat tolerance to the grass.
The viruses that are the most well-characterized are those that cause disease in humans or plants, but Dr. Roossinck estimates that only 1% of all viruses cause disease. In previous surveys of viral genomes, most of the genes identified were completely novel, with no hits in GenBank. Hence, Dr. Roossinck believes that viral genome sequences will provide a rich source of new proteins with unknown functions.
The project is focusing initially on plants that are related to major crop species. The researchers take plant samples back to lab, isolate total nucleic acid, treat with DNase, and look for double-stranded RNA, the hallmark of 80% of plant viruses. This approach is taken because double-stranded RNA in plants is rare except for that produced by viruses. On average, about 60% of the samples yield viral dsRNA. The dsRNA is amplified to DNA by PCR using random hexamer primers and reverse transcriptase. The resulting samples are contaminated with ribosomal genes and other plant genes, but the group has succeeded in obtaining a lot of viral sequences. The group is currently working on obtaining sequence and analyzing the data.
Dr. Roossinck spoke about this project in 2007 at the Center for Biodiversity and Conservation’s Twelfth Annual Symposium at the American Museum of Natural History. The topic of the symposium was Small Matters: Microbes and their Role in Conservation.
Microbe World Radio is sponsored by the American Society for Microbiology, of which I am a member. The shows are produced by Finger Lake Productions. Daily podcasts are available through iTunes and other podcast providers. Archives of Microbe World Radio shows can be found here and here.
Video and audio presentations from the Center for Biodiversity and Conservation’s Twelfth Annual Symposium are available here.
March 01 2008 | Biology | Comments Off
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