European Life Sciences Infrastructure for Biological Information Safeguarding the results of life science research in Europe Niklas Blomberg, ELIXIR Director ELIXIR

2 medicine environment bioindustries society To build a sustainable European infrastructure for biological information, supporting life science research and its translation to: ELIXIR’s mission

3 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

Nature, June 6, 2012 Nature, June 10, 2012 Cell, March 16, 2012Nature, June 6, 2012 ”Big biology” is having impact on drug discovery. The Challenges in retrieving and analysing the data are real

5 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.

6 Matching the treatment to the cancer One in 10 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.

A Life-science infrastructure of Interoperable and integrated data-services ”Efficacy”: Anti-inflammatory effects in right tissue ”Side-effects”: Increased adipogenesis Bone resorption … experiments assays 142 genes w linkage to glucocorticoids 1180 papers ”GR and COPD” in 2012 P ChEMBL Gene Ontology Uniprot UMLS TrialTrove GeneGo Litterature PDB ExpressionAtlas Will the improvement we see in a LPS-challenged mouse translate to a measurable clinical benefit? What are the gene expression changes seen after selective p38 inhibition?

Expression Atlas: A resource of annotated Functional Genomics experiments + What are the gene expression changes seen after selective p38 inhibition?

ChEMBL: Small molecule interactions resource Protein : Small Molecule interactions (including drugs and registered Small molecules) IC50, Kis, vs Assays Target Proteins (when known) Human, Mouse, Rat Links to PDBe, Expression Atlas, Ensembl

10 What is biocuration? Biological knowledge from the literature is encoded in knowledgebases using standard identifiers, ontologies, and controlled vocabularies. Biocuration of literature recovers existing knowledge that is ‘lost’ in papers and not evaluated within a global context => powerful queries within and across knowledgebases => linking and exploration of existing data

11 What Swiss-Prot biocurators Do is what The monk did long time ago

12 Swiss-Prot biocuration efforts Protein sequence and functional annotation Gene Ontology annotation Gene Ontology annotation Pathway and reaction annotation Pathway and reaction annotation Protein interaction annotation Protein interaction annotation Evidence-based proteomics annotation Evidence-based proteomics annotation

The data deluge

genomes Disease cohorts UK10K Finnish Project - to sequence 8000 Finns Faroe Islands – to sequence all population (50K) German and Spanish large scale cohorts International Cancer Genome Consortium - 20,000 high coverage genomes in 5 years for research Rotterdam cohort? Many others……. Current Human Variation Projects

Life-science and data infrastructure in 5 years Data production and using at a large number of sites across Europe (Illumina HiSeq sales up 40% in Q1 2o13?) Human genomics projects but also plants, microbiota, environmental marker organisms Metabolomics & Proteomics coming of age UK National Phenome facility 26 M people employed in health care sector? Integrating genomics into nursing practice Be scalable to 1000s of sites Deal with incomplete, conflicting, and incorrect data

A distributed infrastructure that serves society, industry and users at a large number of sites 16

A distributed infrastructure to scale with the challenge ELIXIR data infrastructure for Europe’s life science research sector ELIXIR Nodes build local bioinformatics capacity throughout Europe ELIXIR Nodes build on national strengths and priorities

Many Nodes are National Coordination Centres

…other are National Centres.

How will ELIXIR Hub & ELIXIR Nodes work together? ELIXIR Node Research & Develop Bioinformatics services Deliver Services through own “brands” Management of core resources Develop & Deliver training activities Participation in international data consortia Industry Collaboration and support ELIXIR Mgmt & Secretariat Technical coordination across nodes Drive standards development & implementation Policy and Outreach Lead coordinated infrastructure investments Deliver services ELIXIR Hub

Fifteen countries have signed up 15 countries plus EMBL have signed the Memorandum of Understanding (MoU) to participate Countries now work towards signing an ELIXIR Consortium Agreement (ECA) UK Signed ECA September 4 More are expected to follow in the coming months…

Services offered by ELIXIR ELIXIR services are open access and free of charge: Data – Global access to biological data including human, animal, crop and marine: Very large user community (e.g. EMBL-EBI >8 million hits per day)  Tools - Integration of existing tools to enable data access and mining by developing an interoperable tools infrastructure  Training - Deployment of specialist and general training courses and workshops, including eLearning. ‘Train the trainer’ activities for new Member States  Standardisation - Coordinate development of standards for biological and medical nomenclature and controlled vocabularies and ontologies  Industry - Support to industry through localised, bespoke projects and SME training Summary - ELIXIR members co-ordinate their national bioinformatics efforts, reduce fragmentation and providing users with single mechanism sustaining life-science data

Identifying new drug targets ELIXIR pilot: Interoperability of high-resolution protein data at EMBL-EBI and HPA, Sweden The Human Protein Atlas portal is a publicly available database with millions of high-resolution images showing the spatial distribution of proteins in 46 different normal human tissues and 20 different cancer types, as well as 47 different human cell lines.

ELIXIR pilots to address key challenges in biomedical research: 1.Cloud computing “Embassy cloud”: Access reference data in a virtual environment – work as though you are at EMBL-EBI or SIB, Switzerland 3.High-Performance Computing “Lightpath”: Connections for on-demand reference data to remote HPC centres at EMBL-EBI and CSC Finland 2.Authentication & Authorisation Improved methods and processes for access to clinical data

ELIXIR Data IO Pilot - ”LightPath” (EBI / CSC) Aim To explore the routine replication of large scale (Petabyte scale) archives to remote sites To create a separate source of data files for challenging DataIO projects Update: Selection of pilot data transfer technology between EBI and CSC Established of a dedicated light path with NRENs and Geant (in progress) Development of model for future IO needs in the lifesciences in Europe

A. Navarro --- Elixir Nodes Workshop EGA EGA hosts more than 450 studies and discoverability to the 732 that are in both EGA and dbGaP EGA supports more than 400 user requests per month Under the ELIXIR pilot project umbrella, the CRG and the EBI have agreed to “Explore ways in which the CRG’s emerging Node could share responsibility for production of the EGA in future”…... which translates into managing peer database representations of the EGA Project hosted jointly by the Hub and the Spanish node of ELIXIR

ELIXIR bridges life sciences and ICT 27 ICT PROVIDERS GEANT - Network EGI - GRID EUDAT – Data Storage PRACE – Supercomputing Millions of Life Sciences users Other ESFRI Research Infrastructures

BioMedBridges: Ten new biomedical sciences research infrastructures stronger through common links Computational ‘data and service’ bridges between the BMS RIs Interoperability between data and services in the biological, medical, translational and clinical domains Link basic biological research data with clinical research and associated data 28

Future challenges for bioinformatics Sustainable funding Integrating clinical and translational data Managing and interoperate big and heterogeneous data Communicating the impact of personal genomics to individuals

Thank you ELIXIR unites Europe’s leading life science organisations in safeguarding the biological data generated every day in publicly funded research. Learn more at

ELIXIR’s tools will… Harmonise the staggering number of analytical software tools Support typical analyses using multiple tools linked together into data processing 'pipelines' Be developed based on the following principles: discoverability ease of use benchmarking Interoperability 31

ELIXIR’s standards will… 32 Be of vital importance to the success of ELIXIR Be based upon coordinated development, implementation and deployment across Europe Build on existing standards, harmonising them, and where necessary, developing new ones Incorporate : Programmatic access Nomenclatures Controlled vocabularies and ontologies Reporting requirements for guiding deposition and facilitating exchange of information

ELIXIR’s data infrastructure will… Enable full data integration by making the best use of Europe's collective, expanding capacity Establish universal principles for optimisation of existing data capacity to meet rising demand - for example, assessing which data should be stored and made available to users Present a transparent single interface to a distributed infrastructure 33

ELIXIR’s compute infrastructure will… Optimise existing compute architecture to enable storage of vast quantities of homogeneous data Life scientists produce an enormous quantity of heterogeneous data which needs to be integrated An order of magnitude increase in compute infrastructure capacity is needed Without it, Europe’s data infrastructure will not be adequate to respond to the data deluge 34

ELIXIR’s training will… Be adequate to accommodate the increase in demand for training Seek to complement, and build on, user training programmes in the Member States Coordinate training capacity throughout Member Countries Enable the development of new training programmes, including ‘training the trainer’, especially in new accession states Be tailored in accordance with the development and diversification of data resources and tools Optimise a range of training methods including using online resources 35

Partnerships are critical to progress We can only be successful through collaboration with: Academia Industry Funders: UK, European, international levels Example IMI projects: Electronic health records for clinical research Autism: integrating imaging, behavioural and –omics data Semantic integration of pre-clinical data

37 The molecules of life

Embassy Cloud logical view