ayout 1 - EMBL Grenoble

EMBL Research at a Glance 2009
Vertebrate genomics
Paul Flicek
DSc 200, Washington
University, St. Louis,
Missouri.
At EMBL-EBI since 2005.
Team leader at EMBL-EBI
since 2008.
Previous and current research
The Vertebrate Genomics team is a combined service and research group that creates and manages
data resources focussing on genome annotation and human variation. The major service projects
of the Vertebrate Genomics team are Ensembl, the European Genotype Archive, and the Data
Coordination Centre for the 1000 Genomes Project. In support of these projects, we are developing
the specialised, large-scale bioinformatics infrastructure required for each analysis. The team’s
research is on computational genome annotation with a particular focus on the integration of diverse
data types such as extensive comparative sequencing, DNA–protein interactions, epigenetic
modifications, and the DNA sequence itself.
Ensembl (www.ensembl.org) is a comprehensive genome information system featuring an integrated
set of tools for genome annotation, data mining and visualisation of chordate genomes. As
such, it is one of the fundamental database resources used to address questions in medical research
and molecular biology. As of August 2008, there were 39 fully-supported genomes in Ensembl
including human, mouse, chicken, five species of fish, a nematode, and several other
mammalian, chordate and insect species.
The European Genotype Archive (EGA) database provides a permanent archive for all types of personally identifiable genetic data including
genotypes, genome sequence and associated phenotype data. The EGA contains both data collected from individuals whose consent agreements
stipulate data release for specific approved research uses or bona fide researchers, as well as data approved for full public release.
The 1000 Genomes Project (www.1000genomes.org) aims to create a comprehensive and public catalogue of common human genetic variation
in three populations by using next-generation sequencing technology. During 2008, the project conducted three pilot projects to assess
the feasibly of creating a deep and accurate catalogue and develop the necessary tools to manage and analyse the data. The pilot projects included
the sequencing of 180 individuals to 2x coverage; sequencing two trios consisting of a child and both parents to 20x coverage; and targeted
sequencing of 1,000 genes in 1,000 individuals.
In collaboration with the NCBI, the Vertebrate Genomics team is one half of the 1000 Genomes Project Data Coordination Centre (DCC)
and has co-leadership of the project’s data flow group. Over the course of the year the project produced approximately 2 terabases of sequence
(equivalent to 8.5 times the number of nucleotides in the EMBL-Bank sequence archive) at a rate approaching 30 gigabases per day. This data
is collected by the DCC and made available to the 1000 Genome Project analysis group and interested researchers worldwide.
Future projects and goals
Next-generation sequencing methods are having a profound impact.
For example, we have been investigating ways to use short read
transcriptome data in our automatic annotation to support the substantial
amounts of data we expect in the future. The availability of
an increasing number of genome sequences is challenging the comparative
genomics aspects of the team’s work both in terms of scale
and complexity. ENCODE and the 1000 Genomes Project will respectively
provide significant new data into the functional genomics
and variation resources. Future developments for the EGA include
a suite of customised data mining tools, an analysis pipeline infrastructure
supporting uniform analysis of the data in the archive,
and the development (in collaboration with international partners)
of standards for the exchange of genotype data including whole
genome sequences.
An example GenomeView from the European Genotype Archive showing
genomic regions that are significantly associated with type I diabetes.
Selected references
Flicek, P. et al. (2008). Ensembl 2008. Nucleic Acids Res., 36
(Database issue): D707-D71
Johnson, D.S. et al. (2008). Systematic evaluation of variability in
ChIP-chip experiments using predefined DNA targets. Genome Res.,
18, 393-03
Saar, K. et al. (2008). SNP and haplotype mapping for genetic
analysis in the rat. Nat. Genet., 0, 560-566
Warren, W.C. et al. (2008). Genome analysis of the platypus reveals
unique signatures of evolution. Nature, 53, 175-183
Flicek, P. (2007). Gene prediction: compare and CONTRAST.
Genome Biol., 8, 233
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