Learning and exploring Life science through the EBI reosurces and tools BIOQUEST workshop_2011 Vicky Schneider, EMBL-EBI Training Programme Project leader

What is EMBL-EBI? Based on the Wellcome Trust Genome Campus near Cambridge, UKBased on the Wellcome Trust Genome Campus near Cambridge, UK Part of the European Molecular Biology LaboratoryPart of the European Molecular Biology Laboratory Non-profit organisationNon-profit organisation

3 What is bioinformatics?

storing retrieving analysing Interdisciplinary Heart of modern biology

5 Biology is changing Data explosion New types of data High-throughput biology Emphasis on systems, not reductionism Growth of applied biology molecular medicine agriculture food environmental sciences… Growth of raw storage at EMBL-EBI (in terabytes)

The molecules of life The ‘book of life’ DNA contains the information needed to build an organism The ‘book of life’ DNA contains the information needed to build an organism The interpreter RNA translates the DNA code into protein The interpreter RNA translates the DNA code into protein Molecular machines Proteins carry out the functions of life: Catalysts: enzymes enable reactions to occur at body temperature Structural support: keratin and collagen give structure to our tissues Transport: carrier proteins move molecules into and out of cells Defense: antibodies protect us from disease-causing organisms Movement: myosin in muscles enables them to contract Molecular machines Proteins carry out the functions of life: Catalysts: enzymes enable reactions to occur at body temperature Structural support: keratin and collagen give structure to our tissues Transport: carrier proteins move molecules into and out of cells Defense: antibodies protect us from disease-causing organisms Movement: myosin in muscles enables them to contract Nature’s ingredients Small molecules provide building blocks, messengers and helpers: Amino acids: the building blocks of proteins Nucleotides and sugars: the building blocks of DNA and RNA Co-enzymes: pigments such as chlorophyll and haem help imprortant processes such as photosynthesis and respiration Hormones: small molecules such as adrenalin and testosterone send important messages from cell to cell Nature’s ingredients Small molecules provide building blocks, messengers and helpers: Amino acids: the building blocks of proteins Nucleotides and sugars: the building blocks of DNA and RNA Co-enzymes: pigments such as chlorophyll and haem help imprortant processes such as photosynthesis and respiration Hormones: small molecules such as adrenalin and testosterone send important messages from cell to cell

Bioinformatics underpins life-science research 1 Genomes Contain genes 1 Genomes Contain genes 2 Genes are transcribed 5 Proteins interact with each other and with small molecules to form pathways 3 Transcripts translate to protein sequences 4 Proteins form three- dimensional structures 6 Pathways combine to build systems

From molecules to medicine Molecular componentsIntegrationTranslation Genomes Nucleotides Transcripts Proteins Complexes Pathways Small molecules Structures Domains Cells Biobanks Tissues and organs Human populations Therapies Disease prevention Early Diagnosis Human individuals

Example of the importance of biological information to all of us

Genome-wide analysis of crop plants Population growth and climate change are major challenges to food security. Traditional routes to crop improvement are too slow to keep up with this increase in demand. Understanding plant genomes helps us identify which species will be most tolerant to drought, salt and pests while still providing optimum nutrition.

Matching the treatment to the cancer One in ten women in the EU-27 will develop breast cancer before the age of 80. If we can identify patterns of genes that are active in different tumours, we can diagnose and treat cancers earlier.

Tracking the source of infectious disease Methicillin-resistant MRSA (Staphylococcus aureus) infection is a global problem. Transmission of individual clones can be tracked using small variations in DNA sequence. This technology can be used to identify the source of new outbreaks across continents and within wards.

Barcoding life DNA barcodes are short sections of DNA that we use to identify an organism. The Barcode of Life Initiative is developing DNA barcoding as a global standard for identifying species. Applications include: Protection of endangered species Sustaining natural resources through pest control Food labelling

Repurposing drugs for neglected diseases Schistosomiasis is a parasitic infection that affects 210 million people in 76 countries. Resistance is developing to the one available drug. We look at the Schistosome genome to identify the targets of existing drugs. Candidates can be tested for anti-schistosomal activity or used as leads for further optimisation.

15 Lots of data and new types of data Genomes Nucleotide sequence Gene expression Proteomes Protein families, domains and motifs Protein structure Protein-protein interactions Chemical entities Pathways Systems Literature Protein sequence

EMBL-Bank UniProt ArrayExpress Atlas InterPro Pfam Ensembl PDB PDBsum IntAct Reactome IntEnz ProFunc MACiE ChEBI BioModels GenBankPubmed CiteXplore GO BLAST FASTA CATH SCOP PubChem RefSeq VAST GEO Genomes Nucleotide Sequences Protein Sequences Macromolecular Structures Small Molecules Gene Expression Molecular Interactions Reactions & Pathways Protein Families Enzymes Literature Ontologies Patent Resources Sequence Similarity & Analysis Pattern & Motif Searches Structure Analysis STRING

17 EMBL-EBI

18 The five branches of EMBL Mouse biology Monterotondo Structural biology Grenoble Bioinformatics Hinxton Structural biology Hamburg Basic research in molecular biology Administration EMBO Heidelberg 1500 staff >60 nationalities

19 EMBL member states Austria, Belgium, Croatia, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Israel, Italy, Luxembourg, the Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and the United Kingdom Associate member state: Australia

In 2010 it cost €41 million to run EMBL EBI. 20 How is EMBL-EBI funded? EMBL member states (€22.4 M) EU (€7.4 M) Charity (€4.1 M) US Govt (€2.9 M) UK Research Councils (€2.5 M)

21 The Wellcome Trust Genome Campus EMBL-EBI Sanger Institute Sulston Building Cairns Pavilion (shared) Sanger Labs/informatics Data centre Sanger Research Support Facility Thanks to Don Powell, Wellcome Trust Sanger Institute, for providing this image.

EMBL-EBI’s mission statement To provide freely available data and bioinformatics services to all facets of the scientific community in ways that promote scientific progress To contribute to the advancement of biology through basic investigator-driven research in bioinformatics To provide advanced bioinformatics training to scientists at all levels, from PhD students to independent investigators To help disseminate cutting-edge technologies to industry To coordinate biological data provision across Europe 15/09/2015