Small Molecules EBI Bioinformatics Roadshow Gareth Owen, ChEBI group The Jackson Laboratory October 18th 2012

Course Objectives In this course you will learn… How small molecules are stored in databases. How data related to small molecules is stored in ChEBI and ChEMBL and how to query these databases Understand the ChEBI ontology How to access and query enzyme resources at the EBI, using the Enzyme Portal, with a closer look at individual resources such as IntEnz and Rhea How the Metabolights database can be used for storing information about metabolomics experiments

Exercises. Separate exercise sheets for each resource discussed. Help reinforce learning. Work alone or in teams. Solutions will be shown in a run-through before the start of the next session.

Questions Please feel free to ask questions at any time. If you are confused, you are probably not alone. I am be happy to answer all questions, provided you will allow the following responses: “We’ll be discussing that later”. “I don’t know” Please do not deal with emails, etc. during the sessions Please turn off mobiles, or set to vibrate.

EBI Metabolomics and Bioinformatics Resources training workshop The Jackson Laboratory Thursday 18th October 2012 Time Subject 09.00-09.30 Introduction to EBI and EBI search 09.30-10.30 Introduction to ChEBI   Exercises 10.30-11.00 Tea & Coffee/ break 11.00-12.30 ChEBI: Searching and the ChEBI Ontology 12.30-13.15 Lunch 13.15-14.30 The Enzyme Portal, IntEnz and Rhea 14.30-15.00 Introduction to MetaboLights 15.00-15.30 Tea & Coffee break 15.30-16.00 Small molecules and PDBe 16.00-17.00 Introduction to ChEMBL Course Feedback

The EMBL-European Bioinformatics Institute A whistlestop tour

What is bioinformatics? The science of storing, retrieving and analysing large amounts of biological information An interdisciplinary science, involving biologists, computer scientists and mathematicians At the heart of modern biology What is bioinformatics? <NEXT>

Growth of raw storage at EMBL-EBI Biology is changing Growth of raw storage at EMBL-EBI (in terabytes) Data explosion New types of data High-throughput biology Emphasis on systems, not reductionism Growth of applied biology molecular medicine agriculture food environmental sciences… At the EBI we are increasingly aware of the explosion in biological data, due to high throughput technologies, new data types and the move towards integrative systems level analysis. As technologies advance, we can only expect to receive more and more data. Bioinformatics is at the heart of modern molecular biology and this has applications in medicine, the environment and food – all issues in which science can deliver benefits for society.

New types of data Literature Genomes Protein sequence Proteomes Nucleotide sequence Proteomes Gene expression Protein structure Protein families, domains and motifs Chemical entities Protein-protein interactions The EBI is probably unique in the world for its range of data resources and tools, spanning everything from DNA and protein sequence to complex pathways and networks. At the EBI, we separate resource development and provision, which we call services, and research although these two are closely related. Both the research areas and services follow the different areas of focus as shown on the slide. Some of the types of data that are now being collected in a high-throughput way, presenting new challenges for how we organise and store this data. Pathways Systems

What is EMBL-EBI? Bioinformatics research and services institute Non-profit organisation ~ 500 staff Part of the European Molecular Biology Laboratory The EBI is based on the Wellcome Trust Genome Campus in Hinxton, which is near Cambridge in UK. We share the campus with the Sanger Institute. The EBI is part of the European Molecular Biology Laboratory and as part of that, we’re a non-profit organisation. 10

The five branches of EMBL Heidelberg Hamburg Hinxton Basic research in molecular biology Administration EMBO Structural biology Bioinformatics Grenoble Monterotondo 1500 staff >60 nationalities We’re the second largest of the five EMBL sites; there is the main lab and administrative centre in Heidelberg; structural biology labs in Hamburg and Grenoble; mouse biology in Monterotondo, near Rome, and bioinformatics in Hinxton. There are around 1,500 staff within EMBL and about 500 of those work at the EBI. Structural biology Mouse biology

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

The Wellcome Trust Genome Campus Data centre Sanger Institute Sulston building Sanger labs / informatics Cairns Pavilion (shared) EMBL-EBI We’re based on the Wellcome Trust Genome Campus in Hinxton, south of Cambridge, UK, which we share with the Wellcome Trust Sanger Institute. This is a good strategic fit as the Sanger is a major sequencing centre (most famous for sequencing 1/3 of the human genome) with a strong programme in functional genomics. © John Freebury

EMBL-EBI’s Mission 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 EBI shares its central mission objectives with EMBL. The EBI is at the centre of Europe’s efforts to collect, organise and make all types biological data available. We do this by providing services so researchers can access and make sense of the information, by being active in bioinformatics research, by providing training and by working closely with industry.

EMBL-EBI external funding Sources of external funding for the year as of December 2010. The Wellcome Trust also supports us through provision of our buildings. The EBI is supported by money from the 20 EMBL member states – contributes more than half of our funding, but then we are also supported by grants from the EC, UK research councils, the Wellcome Trust and our database collaborators such as National Institute of Health. The UK’s Biotechnology and Biological Sciences Research Council (BBSRC) awarded a further €11.4m in August 2009 in support of EMBL-EBI’s planned role as the central hub of ELIXIR.

Services www.ebi.ac.uk/services

Key facts about services European node for globally coordinated data collection and dissemination projects Core databases produced in collaboration with other world leaders, including NCBI (US), National Institute of Genetics (Japan), Swiss Institute of Bioinformatics, Cold Spring Harbor Laboratory (US) The world’s most comprehensive collection of molecular databases The EBI is the European centre for the collection and dissemination of biological data; we do this in collaboration with other global centres (primarily in the US and Japan but different for each data type); The EBI is probably unique in the world for its range of data resources, spanning everything from DNA and protein sequence to complex pathways and networks.

Principles of service provision Accessibility – all data and tools freely available without restriction, apart from information that could be used to identify individuals Compatibility – we develop and promote the use of standards in bioinformatics Comprehensive data sets – agreements with other data providers ensure that our resources contain comprehensive and up-to-date data; agreements with publishers ensure that published data are placed in a public repository at the earliest opportunity Portability – data and software can be downloaded and installed locally Quality – Our databases are enhanced through annotation and cross-referencing The EBI’s services function to meet the needs of researchers for data deposition, access, analysis and integration. Our data resources differ in detail but they all uphold the same five principles. <NEXT> <NEXT>

Databases: molecules to systems Literature and ontologies CiteXplore, GO Genomes Ensembl Ensembl Genomes EGA Protein families, motifs and domains InterPro Functional genomics ArrayExpress Expression Atlas Nucleotide sequence ENA Macromolecular PDBe Protein activity IntAct , PRIDE Pathways Reactome Protein Sequences UniProt Chemical entities ChEBI The slide shows the core resources at the EBI mapped on to the same arrow to show the range of data you can access through the EBI. The EBI is the European centre for the collection and dissemination of biological data; we do this in collaboration with other global centres such as NCBI, the Institute of Genetics in Japan, the Swiss Institute of Bioinformatics and Cold Spring Harbor. LOTS OF <NEXT> Systems BioModels BioSamples Chemogenomics ChEMBL

Database collaborations Many of the EBI’s data resources are members of international consortia, Some, such as the International Nucleotide Sequence Collaboration, exchange data on a regular basis; others, such as the UniProt Consortium and the GO Cosnortium, work together to produce a single resource.

Functional Genomics Data Society www.fged.org Standards development – international collaborations Genomics Standards Consortium (GSC) http://gensc.org Genome annotation www.geneontology.org Protein sequence www.uniprot.org Nucleotide sequence www.insdc.org HUPO- Proteomics Standards Initiative (PSI) www.psidev.info/ Protein structure www.wwpdb.org Functional Genomics Data Society www.fged.org Cheminformatics www.ebi.ac.uk/chebi Pathways www.reactome.org www.biopax.org Systems modelling standards www.sbml.org Metabolomics Standards Initiative (MSI) www.metabolomicssociety.org

New search service Access from the EBI’s homepage Species selector allows for easy comparison Data organised according to: gene expression protein structure literature The EBI has a new, ‘biologically aware’ search service that we developed in response to the needs of our bench-biologist users. Our intuitive, ‘biologically aware’ search service provides a huge simplification for users exploring the data. For example, if you enter p53 in the search box, you are most likely looking for the (human) p53 gene, rather than the gene encoding a p53-binding protein or a p53-like protein; the new search engine takes this into account, and ranks the results accordingly. From an uncluttered results 'dashboard', you can explore genes, protein sequences, gene expression, molecular structures and the scientific literature. You can still delve into the individual databases and the original experimental data, but can return easily to the results summary. A species selector allows you to compare key information for human, mouse, fly and other species, and the literature results include links to free full-text articles. Explore data, return easily to your results

Goals of the new EBI Search Relevant to ‘wet-lab’ biologists Organises information based around a single gene (or a small number of genes) User-expectation centric (not database centric) Smooth transition to the detailed information in many of EBI’s core databases NOT for bioinformaticians: does not provide programmatic access The EBI's resources include many large-scale databases with high-quality data and information curated by biologists, chemists, biochemists and bioinformaticians. The new search accesses a wide palette of this information from a single query and summarises results in a logical structure. With more than 300 million entries indexed and updated daily, the search provides an efficient gateway to all of the major EBI data collections. The EBI search was developed with major input from working biologists all over Europe. It returns data on gene expression (including a picture of where it is expressed in the body), gene and protein function, the interactions of small molecules, 3D protein structure, orthologues, SNPs and more. Conveniently, the summary can be exported or printed as a concise report, and a unique web address allows users to share the results easily with colleagues. The search is driven by Lucene and DAS technologies.

User support E-mail support – www.ebi.ac.uk/support Online help pages – www.ebi.ac.uk/help eLearning Portal – coming soon If you need help using any of our databases it’s available; if our online support pages can’t answer your question we offer e-mail support and promise to get back to you within 2 working days. Our new e-Learning portal, scheduled to launch in spring 2011, will offer interactive tutorials on how to make the most of EMBL-EBI resources.

Research www.ebi.ac.uk/groups As well as providing services, the EBI does research…

Key facts about research at EMBL-EBI A unique environment for bioinformatics research Nine dedicated research groups Seven services teams also carry out R&D Research and services are mutually supportive Our research topics complement those of our services

Dietrich Rebholz-Schuhmann Research themes Text mining Dietrich Rebholz-Schuhmann Genomes Nick Goldman Ewan Birney Paul Flicek Proteins Janet Thornton Rolf Apweiler Gerard Kleywegt Transcriptomes Anton Enright John Marioni Alvis Brazma Chemistry Christoph Steinbeck John Overington The slide shows the core resources at the EBI mapped on to the same arrow to show the range of data you can access through the EBI. The EBI is the European centre for the collection and dissemination of biological data; we do this in collaboration with other global centres such as NCBI, the Institute of Genetics in Japan, the Swiss Institute of Bioinformatics and Cold Spring Harbor. Service team leaders who also have research groups are in italics Pathways and systems Nicolas Le Novère Nick Luscombe Paul Bertone Julio Saez-Rodriguez 34

Training www.ebi.ac.uk/training Our third mission is to provide training…

Pre- and postdocs at EMBL-EBI EMBL International PhD Programme Postdoctoral fellowships: EIPOD – EMBL-sponsored interdisciplinary fellowships ESPOD – EBI–Sanger combined experimental and computational fellowships We also run a one-day intro to the EBI for Masters’ students. Next one is in March; contact training@ebi.ac.uk if interested.

For further information go to: http://www.ebi.ac.uk/Information/Brochures/ EBI in a Nutshell Guide to data resources Research at a Glance 2012