Large Scale Analysis of Transcription Factors Recognition Sites May 19, 2009

In an amazing paper published in Science Express, Bulyk, Hughes and colleagues haved used protein-binding microarrays to determine the DNA-binding specificities of 104 mouse transcription factors.

The most interesting finding of the study is that nearly half of all TF seem to be able to bind two distinct types of sequences. For example, Hnf4a appears to bind to both GGTCA and GGTCCA (and this was confirmed by EMSA). This is also the case for BCL6, which I actively study. They also found several clear cases of dependencies between motif positions (not only adjacent positions).

This study provides a very rich dataset that will be extremely useful for those of us who work on transcriptional regulation.

http://www.sciencemag.org/cgi/content/abstract/1162327v1

The BCL6 transcriptional program features repression of multiple oncogenes in primary B-cells and is deregulated in DLBCL March 23, 2009

This is the title of our latest paper in Blood, which is also my first one at Weill Cornell and my first one as (joint) corresponding author.

http://bloodjournal.hematologylibrary.org/cgi/content/abstract/blood-2008-12-193037v1

Mining the Deep Web February 23, 2009

There’s a pretty interesting article in the NY Times about the Deep Web, that is, the data that is stored in databases and available through web interfaces. The article mentions some of the strategies that scientists (and web search companies) use to mine the Deep Web. Essentially, these strategies involve making a first few queries in order to guess the type and structure of the data contained in a given database, then either building a model of the data or making many more targeted queries in order to essentially map out the content of the database. This type of research is particularly interesting for us biologists, since we use many such databases (pubmed, genome browsers, database of gene expression, etc), and these databases are not at all connected with each other. Clearly, tools that automatically query and integrate data from the Deep Web would be very useful for us.

http://www.nytimes.com/2009/02/23/technology/internet/23search.html

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.

The US Senate wants to increase NIH funding February 4, 2009

Update Feb 18th. Here is more information about how the stimulus money is going to be spent, from Nature :

“National Institutes of Health: $7.4 billion divided among the agency’s scientific institutes and centres will fund grants from a backlog of 14,000 investigator-initiated ‘R01′ grants already reviewed and categorized as “highly meritorious”. It will also fund new R01 applications for projects that could reasonably make progress in two years. The agency will add supplemental funding to existing grants and fund new “challenge grants” aimed at thorny problems.

…

Kington notes: “We are being very careful to focus on funding that only covers the two years of the stimulus package. There will be relatively little, if any, money that entails a four-year commitment.” “

Source: http://www.nature.com/news/2009/090218/full/457942a.html

New Journal: Genome Medicine January 29, 2009

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

http://genomemedicine.com/

Seminars in Computational and Systems Biomedicine at the ICB January 25, 2009

I am co-organizing the new Seminars in Computational and Systems Medicine. David Botstein was our inaugural speaker and both talking to him and hearing his seminar about the coordination of growth rate, cell cycle, stress response and metabolic activity in yeast  has been a fantastic experience (his seminar was much more thought-provoking than it sounds).

We are very pleased and honored to have the following speakers coming next :

February 6 – Isidore Rigoutsos
March 6 – Jason Mezey
April 3 – Olga Troyanskaya
May 15 – Dana Pe’er
June 26 – Alexandre Morozov

The seminars will be held in LC-504 (1300 York Avenue, 5th floor). All seminars will be on Fridays at 3pm. You can email me at ole2001@med.cornell.edu for more information.

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

Two interesting papers related to our research October 30, 2008

Pat Brown (the inventor of microarrays) just published a paper in PLoS Biology in which he described the identification of mRNA targets for 40 RNA-binding proteins. Not only it’s a very interesting study that emphasizes the extent of post-transcriptional regulation, but they also extensively use FIRE for motif discovery ( along with their homebrewed approach)

Hogan DJ, Riordan DP, Gerber AP, Herschlag D, Brown PO (2008) Diverse RNA-Binding Proteins Interact with Functionally Related Sets of RNAs, Suggesting an Extensive Regulatory System. PLoS Biol 6(10): e255

The other paper in Nature by Ruschlow and colleagues describes a protein that binds to a putative reglatory element (CAGGTAG) that we identified in our collaboration with Eric Wieschaus as highly over-represented upstream of the earliest zygotic genes in the Drosophila embryo (De Renzis, Elemento et al, PLoS Biology, 2007).They used one-hybrid assay to identify the zinc finger protein called Zelda.

Liang HL, Nien CY, Liu HY, Metzstein MM, Kirov N, Rushlow C. The zinc-finger protein Zelda is a key activator of the early zygotic genome in Drosophila. Nature.

Postdoctoral positions in computational genomics at Weill Cornell Medical College August 11, 2008

Here’s the ad. A computational biologist will already join my group in the fall (jointly hired with another group at Weill Cornell that produces massive amounts of genomic data).

Olivier Elemento’s computational biology group at the Weill Medical College of
Cornell University in Manhattan, New York, has several openings for postdoctoral scientists.
The group’s research emphasis is on human regulatory genomics and
proteomics. We develop innovative computational tools and approaches to
generate testable hypotheses and discover fundamental principles in
transcriptional, post-transcriptional and post-translational regulation of gene
expression.
Our research is done in close collaboration with experimentalists at Weill and
elsewhere and our ultimate goal is to develop translational research towards
novel understanding and therapy for diseases such as cancer and
neurodegenerative disorders.

For more details on the group’s research, please consult :

http://physiology.med.cornell.edu/faculty/elemento/lab/

Strong analytical and programming expertise is required. Preference will be given
to individuals with a proven track record in computational genomics. Individuals
with strong computational skills and experimental background are also
encouraged to apply.
To apply, send a resume in addition to names and contact addresses of two
persons who can provide recommendation letters to ole2001@med.cornell.edu

And if you join my group, this is the kind of projects you could be working on.