CNIO participates in the ENCODE project: A stride forward in biomedical research

(Press-News.org) The international Encode project, a collaborative study bringing together hundred of scientists from all round the world, including researchers working at the Spanish National Cancer Research Centre (CNIO), published results yesterday mapping the control and regulation of genome activity. These results indicate a total of four million 'switches' controlling the gene activity of 147 types of human cells and tissue. This map provides us with the first comprehensive vision of the genome as a complex web of interactions, and goes far beyond our initial thinking, which assigned it a linear structure.

CNIO participates in Encode through the Gencode project. Gencode (www.gencodegenes.org), coordinated by Tim Hubbard of the Wellcome Trust Sanger Institute in the United Kingdom, is made up in turn of seven groups, with three European representatives including Roderic Guigó's group at the CRG (Barcelona) and the CNIO group led by Alfonso Valencia. The CRG and CNIO groups involvement in the project is part funded by the Spanish Institute of Bioinformatics (www.inab.org) belonging to the Instituto de Salud Carlos III.

Gencode's mission is to create a reference geneset plotting the mass of information that comes out of Encode. We can say that Gencode supplies the system of references, annotations and coordinates needed to draw up the finished map. These references include the location, level of activity and type of genome-generated products, with regard to both protein-coding genes in their different forms of expression (transcripts) and alternatively expressed variants, and other regions coding for diverse types of RNA instead of proteins and pseudogenes.

The CNIO group, comprising Michael L. Tress, José Manuel Rodríguez, Iakes Ezkurdia as well as Alfonso Valencia, head of the CNIO's Structural Biology and Biocomputing Programme, is tasked with developing and applying the annotation methodology for alternative splice forms. The results of this effort are discussed in one of the papers published in Nature and in related publications in the journals Genome Research and Molecular Biology and Evolution. These findings have helped substantially alter the way we understand the process of translating genetic information into the functional units formed by proteins.

For the CNIO group, forming part of Encode has meant the opportunity to test and refine new methods to unravel the complex problem of gene expression regulation, as well as a magnificent occasion to access information which, we can say, has proved indispensable (and sufficient) to round off analysis of the genomic data produced within the CNIO.

SOME KEY FACTS ON THE ENCODE PROJECT

Encode is a consortium funded by the NIH and headed by the National Human Genome Research Institute (NHGRI) in the United States and the EMBL European Bioinformatics Institute (EMBL-EBI) in the United Kingdom. Encode has mobilised the efforts of 442 scientists working out of 32 laboratories in the United Kingdom, United States, Singapore, Japan, Switzerland and Spain.

This ambitious international scientific partnership follows on from a pilot project which analysed a first 1% of the human genome and laid the technical foundations for what would come later. The results of the Encode pilot, summarised on a Nature front cover in 2007, were hugely impactful and have already collected many thousands of citations.

Full information on the Encode findings appear this week in thirty papers, six in Nature and a further 24 in journals such as Genome Research, and will simultaneously be made available through numerous servers and public information systems.

These results are already the touchstone for any existing or future genome study, including personalised cancer genomic initiatives. Indeed, recent evidence has found a close relationship between alterations in the switches regulating genome activity and the appearance of cancers, underscoring the study's importance from a biomedical perspective.

A prime example of this connection are the mutations observed in genes involved in the processing of genomic information in patients with chronic lymphocytic leukaemia, as recently discovered by the Spanish consortium forming part of the International Cancer Genome Project (CLL-ICGC, Nature Genetics, 2011).

### END