The European Molecular Biology Laboratory (EMBL) is supported by sixteen countries. Consists of the main Laboratory in Heidelberg (Germany), Outstations in Hamburg (Germany), Grenoble (France) and Hinxton (U. K.), and an external Research Programme in Monterotondo (Italy). from from 1996

The EBI Mission  To provide Bioinformatics Facilities for the Scientific Community  To become a flagship laboratory for research in bioinformatics  To provide bioinformatics training  To help disseminate standards & technologies

Role of Bioinformatics  To Support Experimental Biology  To Collect and Archive Data  To provide Framework and Integration  To give Easy Access to Data  To make New Discoveries through Data Analysis  To predict through modelling  To facilitate application and exploitation of academic research in Medicine, Agriculture, Health and Environment

Dramatic Changes in Biology over last 5 years  Data Explosion & New Types of Data  Move towards High-Throughput Biology  Move towards Systems Biology  Much larger community – often naïve users  Growth of Applied Biology – molecular medicine, agriculture, food, environmental sciences

Genomes Hypotheses and in silico models Bioinformatics Expression- profiling Comparative genomics Mutant/RNAi data Metabolic data Literature Proteome data Biochemistry

Molecules to Cells to Organisms E.coli Genome Protein Genomes

Systems Biology Output Input CheZ CheW CheB ATP ADP Pi Methyl CheR Methyl Adaptor Flim C Pi CheY CheA

Molecular Basis of Disease p53 tumour suppressor core domain – cancers of many types Cu-Zn Superoxide Dismutase - Autosomal dominant Amyotrophic lateral sclerosis

From Structure to Functional Annotation

PQS biological assemblies MSDchem ligand data Electron Density Visualisation AstexViewer MSDPro, MSDlite SSM fold matchingSurface MatchingMSDsite Active sites Linking to Domain data, eFamily Sequence Mapping, SIFTS

From Structure To Biochemical Function Gene  Protein  3D Structure  Function Given a protein structure:  Where is the functional site?  What is the multimeric state of the protein?  Which ligands bind to the protein?  What is biochemical function?

High throughput  A new sequence every 4 seconds  web requests a day  users  5-10 core databases  cross-references  About 160 other databases

Data Growth

Web requests per day (excluding Ensembl)

ftp year million files; Terabytes

Web Servers Requestsmillions

Distinct hosts served Number users(millions)

dynamic pages domains (2005) 1..uk (United Kingdom) 21.14% 2..com (Commercial) 17.16% 3. [unknown domain] 13.37% 4.[unresolved numerical addresses] 11.05% 5..edu (USA Higher Education) 5.29% 6..net (Networks) 5.27% 7..fr (France) 4.76% 8..it (Italy) 4.68% 9..de (Germany) 2.81% 10..nl (Netherlands) 2.00%

The Services of the EBI  Nucleotide sequences  Genes  Transcription information  Protein sequences  Protein families  Macromolecular structures  Molecular interactions  Pathways  Metabolic information  Scientific Literature

Structure of EBI: Services

Apweiler, Stoesser Brazma Birney Henrick Database Integration and External Services Lopez Stoehr, Zhu

Structure of EBI: Research

Text MiningComputational Genomics Structural Proteomics Neuroinformatics Phylogeny & Evolution

EBI DATA BASES

EMBL-Bank DNA sequences

SWISS-PROT + TrEMBL Protein Sequences

EMBL-Bank DNA sequences SWISS-PROT + TrEMBL Protein Sequences EMSD Macromolecular Structure Data

EMBL-Bank DNA sequences SWISS-PROT + TrEMBL Protein Sequences Array-Express Microarray Expression Data EMSD Macromolecular Structure Data

EnsEMBL Human Genome Gene Annotation EMBL-Bank DNA sequences SWISS-PROT + TrEMBL Protein Sequences Array-Express Microarray Expression Data EMSD Macromolecular Structure Data

EnsEMBL Human Genome Gene Annotation EMBL-Bank DNA sequences SWISS-PROT + TrEMBL Protein Sequences Array-Express Microarray Expression Data EMSD Macromolecular Structure Data IntAct Protein Interactions

GKB Pathways EnsEMBL Human Genome Gene Annotation EMBL-Bank DNA sequences SWISS-PROT + TrEMBL Protein Sequences Array-Express Microarray Expression Data EMSD Macromolecular Structure Data IntAct Protein Interactions

Integration

Integrative science demands integrative resources  EBI databases have a backbone of integrative links  cross-references support trans- database navigation  Is this good enough?  sparse and coarse-grain  not straight-forward to use

Integrative science demands integrative resources Major efforts involved in integration  Interpro: database of protein families, domains and functional sites.  Interg8: data integration project co-ordinated by the EBI, to provide an integrated layer for the exploitation of genomic and proteomic data.  GRID technologies

European Patent Office  Support the inclusion of sequence data in the public databases  Development of tools to capture sequence data  Run their searches at the EBI  (similar arrangements in USA and Japan ensure exchange)  Analogous systems being developed for structure information

Industry Support

 Current successful Industry programme for Pharma  Quarterly meetings  R&D Training - workshops  Industry Forum  Funded by subscriptions  New SME programme under development

New Data Expression Data Proteomic Data Metabolome Data Chip-on- Chip AtlasesElectron tomographs Human Variation Disease Links ??

The Magic Search Box