Poplar genome now supported in FIRE February 5, 2009

My lab doesn’t work on plants, but following a request from somebody in Malcom Campbell’s lab at U of Toronto, I’ve just added the Poplar to the list of organisms supported by FIRE.

The genome data comes from http://genome.jgi-psf.org/Poptr1_1/

To analyze Poplar expression data, you’ll need to download FIRE, then download the poplar_data.zip file from http://tavazoielab.princeton.edu/FIRE/

I tested it on a clustered dataset of Poplar tissue expression profiles (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE6422), and I got very impressive results. The test expression profile is included in the EXPFILES directory in poplar_data.zip file.

New Journal: Genome Medicine January 29, 2009

The very first issue of this exciting new journal is out:

http://genomemedicine.com/

Discovering gene fusions in cancer using deep sequencing January 15, 2009

Chinnaiyan and colleagues have combined 454 and Solexa sequencing to identify transcripts resulting from gene fusion, both in cancer cell lines and primary tumors. The approach relies on deep sequencing the cancer transcriptome and looking for reads that show partial alignment to exon boundaries from different genes. When applied to prostate cancer cell lines and tumors, it detects the well-known TMPRSS-ERG fusion but also discover several novel fusions. It is likely that this approach will lead to the discovery of many novel oncogenes in the near future.

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature07638.html

Determining nucleosome positions using Solexa sequencing March 9, 2008

In this amazing Cell paper, Keji Zhao and his colleagues used Solexa sequencing to create genome-wide maps of nucleosome positions in resting and activated human T cells. They digested DNA with micrococcal nuclease, then gel-purified ~150bp fragments (DNA fragments wrapped around nucleosomes are ~147bp-long) and ran their sample through the Solexa pipeline. The Solexa technology allows the 5′ and 3′ ends (~25bp) of these fragments to be sequenced, and these reads are then mapped onto the human genome.

The resolution of the results they got provides some fascinating insights into chromatin structure and regulation, and the link with gene expression. They detected 8 phased nucleosomes surrounding the TSS of expressed genes, but only right upstream (+1) of the TSS of non-expressed genes. The 5′ end of +1 nucleosomes peaked at +40bp for expressed genes, but +10bp for non-expressed genes. Nucleosome levels at -1 were lower than -2 and +1 for both expressed and non-expressed genes, suggesting that all core promoters are nucleosome-depleted. -1 levels of induced genes do not appear to change upon T cell activation, however increases in -1 levels were observed for repressed genes (-1 nucleosome levels appear inversely correlated to RNA Pol occupancy, also measured by ChIP-seq). The lists goes on and on.

While the authors focus their paper on nucleosome patterns surrounding the TSS, to me, nucleosome patterns in the rest of the genome would be more intriguing. What kind of nucleosome patterns are found in gene deserts ? in recombination hotspots ? in ultra-conserved sequenced ? they present anecdotal evidence that enhancer regions need to be nucleosome-free, in order for regulatory elements to be able to recruit transcription factors. It would be interesting to see if this is a general feature of enhancers (which would then allow to predict where they are in the genome).

23andMe December 9, 2007

According to The Economist, at least 3 companies (23andMe, deCODE, Navigenics) offer a new type of service where they will genotype several hundred thousand common SNPs from a DNA sample (e.g. saliva) you’ll provide. All this for a few thousand dollars or even less than $1,000, depending on the company. This is an interesting development, especially for us, scientists: if it catches on, the prices for this kind of services and associated technology will go down, and this will make it significantly cheaper to conduct whole-genome association studies with large cohorts of patients. This may also bring down sequencing costs even further and favor innovation in sequencing technology.

I have to say, I am tempted to try out one of these services. There are no genetic diseases running in my family, so I have no reason to be particularly afraid of discovering something bad (yeah yeah spontaneous mutations). I am just very curious to get a sense of what my genome looks like, and of how it differs from other genomes (from the HapMap people for example). Of course, SNPs are particularly interesting when they can be correlated to some phenotype, that is, if they can explain why we look the way we look, or predict disease risks. Provided customers of these services will be willing to give out enough details about themselves (with minimum self-reporting, and maximum objective tests), the companies offering these services could end up making significant discoveries in terms of genotype-phenotype associations.

Would I make my SNPs publicly available ? probably not. This is America, and like the article says, it does not sound inconceivable that health insurance companies will one day deny you coverage because you have an allele associated with increased risk for a certain disease. If doing a little research on the web can save them several hundred thousand dollars, it would be crazy to think they wouldn’t do it. Of course, I can always move back to a country that has universal health insurance if this happens

Grapevine genome sequenced August 29, 2007

(The sequenced strain was derived from Pinot Noir – decent but not my favorite )

http://www.nature.com/nature/journal/vaop/ncurrent/abs/nature06148.html