Professor Ewan Birney FRS Director, EMBL-EBI

Transcription

1 Infrastructures for research and innovation Professor Ewan Birney FRS Director, EMBL-EBI

2 Outline of talk Who Am I, What is EMBL? The change in genomics The needs for stratified patients in clinical care and drug discovery Europe s assets A path to releasing Europe s strengths

3 The European Molecular Biology Laboratory 80+ nationalities Heidelberg, Germany >1600 personnel 6 sites in Europe Hinxton, Cambridge, UK Grenoble, France Main Laboratory Bioinformatics Structural Biology Tissue Biology, Disease Modeling Neuroscience Structural Biology Barcelona, Spain Rome, Italy Hamburg, Germany

4 Ewan Birney Lead the original team that analysed the human genome (gene sets) Algorithm research in genomic information Set up many key databases in genomics (eg, Ensembl) Director of EMBL-EBI Non-executive director for Genomics England (NHS clinical genomics) Formal Advice to UK, Finnish, Danish, US governments; informal to other governments Advisor to both large (GSK) and small (Oxford Nanopore) companies Chair of the Global Alliance for Genomics and Health (GA4GH)

5 We have been living through a revolution.

6 One genome 2003 to 2018 The cost of sequencing a genome in 2003 The cost of sequencing a genome in 2018

7 Imaging: new technologies change the game EM tomography, Atomic-scale models from EM Super-resolution light microscopy High-resolution MRI and CT Light sheet microcopy

8 Genomics: from research to healthcare Research English language Light-weight legal Similar systems Open data Publications Grant funding Practicing Medicine National language Heavy legal framework Different systems Closed data Not published Contract funding

9 Big numbers!

10 Stratification of Patients

11 Stratification Class A Stratification Class B Class C

12 Benefits of stratification In clinical practice Better diagnosis and prognosis Better use of (expensive) medicines ( personalised medicine) Specific care pathways optimised for the cases In drug discovery More clarity on the therapeutic goals in early development Cheaper and more likely to succeed Phase II and Phase III trials

13 4 Pillars of stratification At scale genomic assays Clear legal basis to access appropriate data and approach patients Very Large Virtual Cohorts ideally with population scale ascertainment Harmonised representation of key aspects of EHRs

14 Europe s Assets

15 Well regulated, often state run healthcare Total population size of >200 million The largest coherent EHR records in the world (Denmark, 6 million Danish citizens) Sweden, Norway, Finland all have good record keeping Large, predominantly state run systems in France and UK Historical as well as future health data

16 The most advanced clinical + population genomics programs globally Finland - >10% of the population sequenced in 5 years Estonia aiming for all 1 million biobanked Denmark 5Million EHRs, 100,000 sequenced UK Goal of 5 million with genomic assays within 5 years France Clinical + Population scale assays for ~1 million within 5 years Spain Variety of regional programs with scale to millions

17 An European Framework: MEGA

18 ELIXIR Node Map Associated Institutes Genomic Infrastructure ELIXIR-BE Katholieke Universiteit Leuven EMBL-EBI ELIXIR-BE University of Antwerp ELIXIR-BE University of Liège World leader in genome ELIXIR-BE Vrije Universiteit informationbrussel and analysis ELIXIR-BE Universiteit Hasselt The most comprehensive Interuniversity lifescienceelixir-be datasets Institute of Bioinformatics globally Brussels ELIXIR ELIXIR-CZ: Masaryk University (CEITEC) Masaryk European ELIXIR-CZ: wide(cerit-sc) network University with National nodes to ELIXIR-CZ: Institute of Chemical Technology connect local research ELIXIR-CZ: Institute of and healthcare Experimental Botany AS CR, v. v. i. ELIXIR-CZ: Institute of Molecular Genetics of the AS CR ELIXIR- CZ Institute of Microbiology ASCR

19 The need for infrastructure Clinical Record + Diagnosis Reference Infrastructure National Genome Database

20 A vibrant commercial research sector Many European large scale pharmaceutical companies Sanofi, GSK, Roche, AstraZeneca, Novartis Balance of US vs European research intensity Vibrant SME community Based around clusters Heidelberg-Stuttgart-Munich-Basel, Paris-Brussels-Amsterdam, Oxford-London-Cambridge, Barcelona, Stockholm-Helsinki Public-private partnerships IMI

21 A path for European stratified populations

22 Alignment of European programs Million genomes declaration EMBL-EBI and ELIXIR (ESFRI) as genomic infrastructure IMI programs as an instrument to foster crossinstitutional, trans-national, public-private partnerships

23 Engagement with Nation state Health strategy Practical on the ground implementation is in the hands of the operations and regulation of the healthcare systems in Europe Source of EHR information Source of genomic information Fundamental need to have >100 million person cohorts will drive trans-national work Clear for smaller countries that between country federation is needed Clear for rare disease in all countries; will become relevant to more diseases

24 Engagement with global structures Europe has to tackle trans-national coordination far earlier than the US or Chinese systems Similar opportunity as mobile phone GSM standards the need for ultimately trans-national access places Europe as the leader in how to solve this Legal and ethical components (GDPR) Technical components Leadership in global bodies, such as GA4GH (Global Alliance for Genomics and Health)

25 Thank you! EMBL-EBI Follow me on 1/11/

26 Our mission Deliver excellent research Deliver scientific services Train the next generatio n of scientists Engage with European industry Coordinate bioinformatic s in Europe

27 Life science: many data types Genes, genomes & variation Gene, protein & metabolite expression Protein sequences, families & motifs Phenotypes Macromolecular structures Interactions, reactions & pathways Chemogenomics & metabolomics

28 Data resources at EMBL-EBI Gene, protein & metabolite expression Genes, genomes & variation Ensembl Ensembl Genomes GWAS Catalog Metagenomics portal Expression Atlas Metabolights PRIDE RNA Central Protein sequences, families & motifs Literature & ontologies InterPro Pfam UniProt Molecular structures Protein Data Bank in Europe Electron Microscopy Data Bank Chemical biology Experimental Factor Ontology Gene Ontology BioStudies Europe PMC ChEBI ChEMBL SureChEMBL Systems BioModels BioSamples Enzyme Portal IntAct Reactome Molecular Archives ~410 people Worldwide collaborations European Nucleotide Archive European Variation Archive European Genome-phenome Archive ArrayExpress

29 Global reference data See the live map at

30 Big data, big demand ~27 million requests to EMBL-EBI websites every day Scientists at over 3.2 million unique IP addresses use EMBL-EBI websites EMBL-EBI delivered 1-5 US$ billion in efficiency savings worldwide Sustainable Funding Over 40 difference funding agencies worldwide Forward commitment of over 100 million

31 Research groups at EMBL-EBI Alex Bateman Ewan Birney Pedro Beltrao Alvis Brazma Rob Finn Paul Flicek Andrew Leach Moritz Gerstung Nick Goldman Zamin Iqbal John Marioni Evangelia Petsalaki Oliver Stegle Janet Thornton Virginie Uhlmann Daniel Zerbino

32 Research data at EMBL-EBI Mutations affecting proteins implicated in rare diseases Evolution of Proteomic & RNA comparison phosphorylation sites Genomics of infectious disease > < Modeling unwanted variation in single-cell transcriptom e studies

33 Single Cell Genomics

34 Translational bioinformatics

35 EMBL Research Community Research group picture ~170 people ~50 visitors / year

36 Medical Genomics

37 Serious efforts on way Genomics England 100,000 Genomes by end of 2019 (35,000 done now) Long term 60K-100K from routine healthcare across NHS Plan France Génomique ~100,000 genomes / year by 2025, first sites selected Iceland 40% of the population genotyped/sequenced + imputed Switzerland SPRT program to promote genomic medicine Finland at least ~10% (0.5 million) of the population with sequence data by 2020 US Complex payer/insurance lead market Mixture of HMO (Geisgner) and NIH (All of Us mainly a cohort)

38 Genomics: from research to healthcare Research English language Light-weight legal Similar systems Open data Publications Grant funding Practicing Medicine National language Heavy legal framework Different systems Closed data Not published Contract funding

39 Bridges need at least two anchors

40 Long-term goals Ideal: Institute for Biomedical informatics in each country Large nations/populations: Distributed network with a clear centre of gravity EMBL-EBI & ELIXIR handle research data: reference collections and sharing amongst researchers (including clinical) Institute for Biomedical Informatics: Responsible for exploiting molecular reference data Provides the national link and point of reference (eg, around legislation) Broker for research data (back to EMBL-EBI, NCBI & ELIXIR)

41 France EMBL-EBI

42 Basic Research Working collaboratively with Elixir-France Orphanet, CAZy Support training in bioinformatics Ensuring French scientists and institutes exploit EMBL- EBI Seamless APIs to allow submission of data driven by institutes (less complexity for user/scientist, use EMBL-EBI as backup) GDR Mediatec for Chemical Ecology -> Metabolights Genscope DNA data -> ENA Research work with French research scientists Institute Pasteur, Institute Curies links French Embassy internships at EMBL-EBI

43 Applied Research : Medicine Ensuring transfer of skills and expertise to the French medical system France s medical genomics must be run and delivered in France (obviously!) Technical aspects, eg, Archiving DNA data at scale nationally Reference human biology resource Orphanet Infectious epidemiology/bacterial genome sequencing? Working with Elixir-France and others for international standards ELIXIR s role in GA4GH standards

44 Big numbers!

45 Global standards: the GA4GH GA4GH is THE standards-setting body for genomics and healthcare Embraces federated approach Setting community standards early Cloud: Analysis carried out where the data lives You re already using it! : SAM/BAM/CRAM/VCF formats Tools: htsget the first step away from file-based access Rare disease diagnoses: Matchmaker Exchange Federated discovery: GA4GH Beacons

46 Federation Open research data analysis Healthcare data with research use analysis Aggregate data globally Analyse data locally (via VMs) Download, analyse locally Collate analyses