28 May, 2008

Ensembl 50

Ensembl is now busy with preparations for our next release, Ensembl 50! We're working hard and we'll keep you updated on what's in store for this release. Our biggest new development will be our revamped website. As usual, we have updated some species and provided new data for other species. Keep reading for an outline of what we aim to provide in Ensembl 50.

New web interface:
The most exciting change in Ensembl 50 will be a new web interface: Simpler, Better, Faster is what we're aiming for. Not only will pages take less time to load, but they will also look a little different. We're hoping that we will have improved the navigability and discoverability of the site so that you can make the best use possible of the data we provide. We have taken into account your messages at helpdesk and your voices in courses. Let us know what you think by emailing helpdesk@ensembl.org !

Genebuild team:
In terms of new data for Ensembl 50, we have constructed new gene sets for tetraodon and cow. Vega/Havana (manual annotation) has released new gene sets for human and mouse so these will be displayed on our website alongside Ensembl genes.

For human, you may know that Ensembl and Havana merge identical transcripts. We have improved the Vega/Havana merge using the latest Havana gene set. Because untranslated regions are notoriously difficult to determine, we've used ditags when predicting UTRs for human. Finally, we have removed some dodgy-looking gene models that were highlighted by the Alpheus project.

For low-coverage genomes, gene models are predicted by projecting the human gene models down onto the 2x genomes. In this release, cat and pika have been updated by projecting current human gene models onto the existing assembly.

We've also updated the gene sets for C. elegans and chimp. Release notes for C. elegans can be found on the WormBase website. Chimp has an updated gene set to include more chimp-specific predictions, and genes projected from human onto chimp are updated.

The horse genomic assembly (EquCab2) has recently been updated such that chromosome 27 has been shortened. This is not a new genebuild as such, but we have modified our data to reflect this change. Zebrafish Agilent V2 Arrays have been mapped to cDNA and genomic sequences.

Canonical transcripts (the longest translations) have been labeled for all species in the database, though this will not appear in the browser. As usual, non-coding RNA genes have also been updated for most species, and cDNA alignments have been redone for human and mouse.

Variation and Functional Genomics teams:
Our Variation team plans to provide updated single nucleotide polymorphisms (SNPs) for tetraodon, cow, human, chimp and orangutan. Our Functional Genomics team will provide promoter cis-regulatory motifs from here. They will also update the current regulatory build on human.

Comparative Genomics team:
Our Comparative Genomics team is extending their multiple alignments with new species and low-coverage (2x) genomes to include:
* 4-species: catarrhini primates EPO (Enredo-Pecan-Ortheus) alignments (human, chimp, orangutan, macaque )
* 12-species: amniote vertebrates Mercator-Pecan alignments (current 10-species alignments + Pongo pygmaeus and Equus caballus)
* 23-species: eutherian mammals EPO (Enredo-Pecan-Ortheus) alignments (all 2X genomes + current 7-species alignments + Pongo pygmaeus and Equus caballus)

GERP scores (% conservation on a basepair level for the 23-species eutherian mammals alignments) will be released.

The Compara (comparative genomics) team is working hard! They're also providing new pairwise alignments:
* All the pairwise (between two species), whole-genome alignments (using tBLAT) will be updated using a new pipeline that follows a best-in-genome approach to filter spurious hits.
* The pairwise alignments for more closely related species (using BLASTz-net) will be updated for the following species so that the reference species is human:
. human vs Pongo_pygmaeus
. human vs Loxodonta africana
. human vs Echinops telfairi
. human vs Oryctolagus cuniculus
. human vs Dasypus novemcinctus
. human vs Myotis lucifugus
. human vs Bos Taurus
. human vs Ochotona princeps
. human vs Felis catus
Sitewise dN/dS values will be provided in our gene trees to detect positions in the alignments that are under different evolutionary pressure.

Web team:
Last but not least, please note that from Release 50 we will no longer be providing the 'ssaha' sequence search. If you wish to run your own 'ssaha' sequence search you can download the files to generate the search hashes from our FTP site. Alternatively, use BLAT (the BLAST-like Alignment Tool) which is equally fast and also demands exact matches.

That's it for now! Any questions, just email helpdesk@ensembl.org. We will be posting more information as the release date gets closer (we are aiming for end of July!)

10 May, 2008

Coming back from CSHL

I'm in the airline lounge about to head back from "Biology of Genomes" at Cold Spring Harbor Laboratory. As always, it was a great meeting; highlights for me was seeing the 1,000 genomes data starting to flow - it is clear that the shift in technology is going to change the way we think about population genomics - and for me, the best session was one on "non-traditional models" - Dogs, Horses and Cows, where the ability to do cost effective genotyping has completely revolutionised this field. Now the peculiarities of the breeding structures, with Dog breeds being selected for diverse phenotypes, Cows with the elite bulls siring thousands of offspring due to artificial insemination and Horses having obsessive trait fixation over the last 1,000 years can really bring power to genetics in different ways. Expect alot more knowledge to come from these organisms and others (chickens, pigs, sheep...) over the coming years.

For my own group, Daniel Zerbino talked about Velvet, our new short read assembler which has also just been published in Genome Research (link). Velvet is now robust and capable of assembling "lower" eukaryotic genomes - certainly up to 300MB from short reads in read pair format. It is also being extensively used by other groups, often for partial, minature de novo assemblies in regions. It went down well, and Daniel handled some pretty tricky questions in the Q&A afterwards. Next up - we get access to a 1.5TB real memory machine, and put a whole human genome WGS into memory. Alison (Meynert) and Michael (Hoffman) had great posters on cis-regulation and looked completely exhausted at the end of their poster session.

From Ensembl, Javier talked about Enredo-Pecan-Ortheus (which we often nickname as EPO) pipeline. As some said afterwards to us "you've really solved the problem, haven't you" - Javier was able to show clear evidence that each component was working well, better than competitive methods, and having a impact on real biological problems, for example, derived allele frequency. Its ability to handle duplications is a key innovation. Javier and Kathryn are current wrestling in the "final" 2x genomes into this framework, from which point we will start to have a truly comprehensive grasp on mammalian DNA alignments. I also like it as Enredo is another "de bruijn graph" like mechanism. Currently the joke is that about 10 minutes into any conversation I say "well, the right way to solve this problem is to put the DNA sequence into a de bruijn graph".

Going to CSHL biology of genomes is always a little wince making though as this field - high end genomics - really prefers to use the UCSC Genome Browser (which as I've written before on, is a good browser, and I take the use of it to be our challenge to make better interfaces for these users on our side). My informal counting of screen shots was > 20 UCSC, 4 Ensembl (sneaking one case of 'Ensembl genes' shown in the UCSC browser as a point for each side) and 0 NCBI shots. Well. It just shows the task ahead of us. e50! - our user interface relaunch - is coming together, and we will start focus-group testing soon - time for us to address our failings head on. I'll be blogging more about this as we start to head towards broader testing.

Lots more to write about potentially - Neanderthals, Francis Collins singing in the NHGRI band (quite an experience), reduced representation libraries with Elliott, genome wide association studies (of which, I just _love_ the basic phenotype measures, from groups like Manolis Dermitzakis) and structural variation... but for the moment I've got to persuade my body to feel as if it is 11.30 at night and see if I can get a good nights sleep on the plane.

02 May, 2008

Year of the rat...

Things are moving within the rat community as this month's Nature Genetics issue shows with a special on rat genetics exploring the latest developments.


  • ENU-induced gene targeting in rats;
  • A 'white paper' discussing progress and prospects in rat genetics;
  • A brief overview on rat genome resources online;
  • ENU-induced gene targeting in rats;
  • A contribution on dynamics of CNV in rat and their impact in phenotypes;
  • A survey of genetic variation from The STAR Consortium (over 3 million newly identified SNPs and over 20,000 SNPs genotyped across 167 distinct inbred rat strains);
  • and several papers focusing on the identification of genetic variants associated to rat models of human disease...
The driving force behind these outstanding achievements can be found on a well interliked rat community bridging resources across the Atlantic: RGD and the EURATools Consortium (FP6 contract number LSHG-CT-2005-019015) collaborations are a good example.

EURATools investigators are developing integrated genome tools (Ensembl is one of the partners of this consortium). Integrating high-throughput sequencing and genotyping with informatics; intensive analysis of phenotypes, gene sequence and gene expression in congenic strains to identify genes and regulatory pathways for a wide range of rat disease phenotypes; and establishing optimised protocols for rat gene targeting are the goals of this ambitious EU funded project.