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http://www.embl.de/ from 1974 http://www.ebi.ac.uk/ from 1996 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). 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 Literature Expressionprofiling Proteome data Metabolic data Bioinformatics Comparative genomics Biochemistry Mutant/RNAi data Hypotheses and in silico models Molecules to Cells to Organisms Protein E.coli Genome Genomes Systems Biology Input AdaptorAdaptor Methyl CheB ATP CheA CheWCheW ADP Pi Pi CheY CheZ Flim C Output Methyl CheR 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 Linking to Domain data, eFamily Sequence Mapping, SIFTS MSDchem ligand data Electron Density Visualisation AstexViewer MSDPro, MSDlite MSDsite Active sites SSM fold matching PQS biological assemblies Surface Matching 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 600 000 web requests a day 100 000 users 5-10 core databases 20 000 000 cross-references About 160 other databases Data Growth Web requests per day (excluding Ensembl) 500000 450000 400000 350000 300000 250000 200000 150000 100000 50000 Dec-02 Sep-02 Jun-02 Mar-02 Dec-01 Sep-01 Jun-01 Mar-01 Dec-00 0 ftp year 2001 2002 2003 2004 2005 million files; Terabytes 4.5 11914 5.6 11809 13.5 43860 17.3 60508 26.3 85396 Web Servers Requests millions 2002 2003 2004 2005 118 255 354 482 118631650 255399724 354235704 482076196 Distinct hosts served Number users(millions) 2002 1586883 1.5 2003 2784974 2.7 2004 3656109 3.6 2005 3919564 3.9 dynamic pages domains (2005) 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. .uk (United Kingdom) .com (Commercial) [unknown domain] [unresolved numerical addresses] .edu (USA Higher Education) .net (Networks) .fr (France) .it (Italy) .de (Germany) .nl (Netherlands) 21.14% 17.16% 13.37% 11.05% 5.29% 5.27% 4.76% 4.68% 2.81% 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 Structure of EBI: Services Database Integration and External Services Lopez Apweiler, Stoesser Stoehr, Zhu Henrick Brazma Birney Structure of EBI: Research Structure of EBI: Research Text Mining Schuhmann Structural Proteomics Computational Genomics Ouzounis Thornton ? Le Novere Neuroinformatics Goldman Phylogeny & Evolution EBI DATA BASES EMBL-Bank DNA sequences 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 Array-Express Microarray Expression Data SWISS-PROT + TrEMBL Protein Sequences EMSD Macromolecular Structure Data EMBL-Bank DNA sequences Array-Express Microarray Expression Data SWISS-PROT + TrEMBL Protein Sequences EMSD Macromolecular Structure Data EnsEMBL Human Genome Gene Annotation EMBL-Bank DNA sequences Array-Express Microarray Expression Data SWISS-PROT + TrEMBL Protein Sequences IntAct Protein Interactions EMSD Macromolecular Structure Data EnsEMBL Human Genome Gene Annotation EMBL-Bank DNA sequences GKB Pathways Array-Express Microarray Expression Data SWISS-PROT + TrEMBL Protein Sequences EnsEMBL Human Genome Gene Annotation IntAct Protein Interactions EMSD Macromolecular Structure Data Integration Integrative science demands integrative resources EBI databases have a backbone of integrative links 20 000 000 cross-references support transdatabase 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 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 Chip-onChip Proteomic Data Metabolome Data Human Variation Atlases Disease Links Electron tomographs ?? http://www.ebi.ac.uk/2can/ The Magic Search Box