2
Alain’s path 1989-now• Basis in molecular biology
• Academia, pharma, medical center, applied research institutes
• Biomarkers / Omics / technologies
• Mechanisms of disease
• Translational medicine
• Personalized healthcare
Senior Scientist Integrator Biomarkers
Scientific lead DTL-Technologies
Chair EATRIS Biomarker Platform
Professor of Personalized HealthcareHead Radboud Center for Proteomics, Glycomics & Metabolomics Coordinator Radboud Technology Centers
Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
Alain’s path 1989-now• Basis in molecular biology
• Academia, pharma, medical center, applied research institutes
• Biomarkers / Omics / technologies
• Mechanisms of disease
• Translational medicine
• Personalized healthcare
Senior Scientist Integrator Biomarkers
Scientific lead DTL-Technologies
Head EATRIS Biomarker Platform
Professor of Personalized HealthcareHead Radboud Center for Proteomics, Glycomics & Metabolomics Coordinator Radboud Technology Centers
3 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
Exponential technology developments in laboratories
• Next generation sequencing• DNA, RNA• Risk analysis and therapy selection
• Mass spectrometry• Proteins, metabolites• Monitoring of disease and treatment effects
• Imaging• Non invasive images, real time
• Spatial view of intact organs and organisms
500
1000
1500
2000
m/z
5 10 15 20 25 30 35 40 Time [min]
4 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
Advances in mass spectrometry• Mass spectrometry analysis of glycoproteins in human plasma
• 1/20 microliter analysis: detection of 1.000.000 signals in one scan (1,4 Gb)
• ~40.000 peptides of which >80% contain sugar modification
• Potential to screen patients and identify new biomarkers?
500
1000
1500
2000
m/z
5 10 15 20 25 30 35 40 Time [min]
Proof of principle study:
Biomarkers !?
5 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
New diagnostic glycoprotein biomarker
• Glycoprofile of intact transferrin protein (80 kDa)
• Identified through combination glycoproteomics and exome sequencing
• Is linked to specific glycosylation disorders (rare metabolic diseases)
• Implemented now in clinical care as diagnostic mass spec test
7 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
8
New data !(generators, owners)
8 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
Exciting next steps: translate laboratory to society
• Point-of-care analysis of few biomarkers
• 1.000.000 signals per proteomics analysis
11 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
implementation
innovation
research
12 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
Irreproducibility of data
{Freedman et al, PLOS Biology, 2015}
{2012} {2011} {2013} {2008}{2012}
13 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
Categories of errors leading to irreproducibility
{Freedman et al, PLOS Biology, 2015}
14 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
Biomarker innovation gaps !
Discovery Clinical
validation/confirmation
Diagnostic
test
Number of
biomarkers
Gap 1
Gap 2
• Too much biomarker discovery• Too little development to application
15 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
Biomarker innovation gaps: some numbers
~ 5 biomarkers/working day
1 biomarker/1-3 years
1 biomarker/2-10 years
Eg Biomarkers in time: Prostate cancerMay 2011: 2,231 biomarkersNov 2012: 6,562 biomarkersOct 2013: 8,358 biomarkersNov 2014: 10,350 biomarkersOct 2015: 11,856 biomarkers Nov 2016: 14,481 biomarkers
Discovery Clinical
validation/confirmation
Diagnostic
test
Number of
biomarkers
Gap 1
Gap 2
16 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
Choice for biomarker scientists: discover or confirm?
17 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
Biomarkers for personalized medicine and health
time for quality, not quantity
18 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
Way forwardQuote Freedman paper:
{Freedman et al, PLOS Biology, 2015}
19 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
Introducing 5 infrastructure communities
(local) (European)
(Netherlands)
20 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
www.radboudumc.nl/research/technologycenters
Genomics
Bioinformatics
Animalstudies
Stemcells
Translationalneuroscience
Image-guided treatment
Imaging
Microscopy
Biobank
Healtheconomics
Mass Spectrometry
RadboudumcTechnology
Centers
Investigationalproducts
Clinicalstudies
EHR dataanalysis
Statistics
Humanperformance
Datastewardship
Molecule
Flowcytometry
3D lab
21
About 280 dedicated people working in 19 Technology Centers, ~1800 users (internal, external), ~150 consortiawww.radboudumc.nl/research/technologycenters/22
• Proteins• Metabolites• Drugs• PK-PD • Preclinical
• Clinical
• Behavioural• Preclinical
• Animal facility• Systematic review
• Cell analysis• Sorting
• Pediatric• Adult• Phase 1, 2, 3, 4
• Vaccines• Pharmaceutics• Cyclotron• Radio-isotopes• Malaria parasites
• Management• Analysis• Sharing• Cloud computing
• DNA• RNA
• Internal• External
• Early HTA• Evidence-
based surgery• Field lab
• Statistics• Biological• Structural
• Preclinical• Clinical
• Economic viability
• Decision analysis
• Experimental design• Biostatistical advice
• Electronic Health Records
• Big Data• Best practice
• In vivo• Functional
diagnostics
• iPSC• Organoids
• 3D imaging• 3D printing• Virtual reality
Link to European infrastructures
23 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
24EATRIS15/02/2017
Filling the gaps (1)
GAP 1Public increasingly funding early development, funding gap remains
Public FundingPrivate FundingMoves away from early development
Fundamental discovery
Early Translational F.I.M
Phase 1 Phase 2 Phase 3
GAP 1
24 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017 www.EATRIS.eu
25EATRIS15/02/2017
Filling the gaps (2)
GAP 2Outputs of publicly funded projects misaligned with privately financed requirements
for further development
Public FundingTechnology push, publications
Private FundingProduct and patient focus, market pull
Fundamental discovery
Early Translational
F.I.MPhase 1 Phase 2 Phase 3
GAP 2
25 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017 www.EATRIS.eu
26EATRIS15/02/2017
Participating countries : CZ, ES,
FI, FR, IT, NO, EE, NL, LU, SI, SE
(Host)
Observer: LV
88 Academic & non-profit
research institutions of
excellence in translational
medicine
EATRIS map
26 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017 www.EATRIS.eu
27EATRIS15/02/2017
Client projects
Infrastructure
Funding Expertise
GMP manufacturingLicensesImaging facilitiesBiobanksClinical trial unitsPatient groups
AcademiaResearch /charitiesSME/biotechPharma
CliniciansLatest technologiesProject managementRegulatoryPartnering
Nat’l governmentsRegional dev. FundsH2020Venture capitalPharma partnering
Landscape
5 Technology Platforms
27 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017 www.EATRIS.eu
28EATRIS15/02/2017
• Chair: Alain, van Gool, Radboudumc/TNO, the Netherlands
• Operational manager: Florence Bietrix
• 46 European advanced biomarker development centres
• State-of-the-art technologies and expertise
• Biobanks
• Assay development and validation
• Multi-centre clinical trials
Biomarkers platform
28 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017 www.EATRIS.eu
29EATRIS15/02/2017
1. Matchmaking & services
• Fast Matchmaking: clarify client’s need, identify relevant institutions,
provide list to PI who contacts the institution(s) directly
• Matchmaking: for researchers with funded projects: identify institution(s) for
service delivery – full support of C&S to reach agreement. The institution
delivers. Contract is between client and institution.
2. Improving pipeline productivity
Collaborating across boundaries to design, validate and roll out novel:
• Funding, operational and collaboration models
e.g. access to early regulatory dialogue
• Tools, technologies and methodologies
e.g. enabling multi-centre, imaging-enabled clinical trials for mAbs &
ADCs with 89Zr
29 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017 www.EATRIS.eu
30EATRIS15/02/2017
TRANSLATIONAL MEDICINE’17, September 24 – 26, Prague
www.eatris.eu
30 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017 www.EATRIS.eu
Introducing 5 infrastructure communities
(local) (European)
(Netherlands)
31 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
Ongoing independent biomarker activities
Europe
USA
{Asadullah et al, Nature Reviews Drug Discovery, Dec 2015}
32 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
NL Biomarker Development Center
Standardisation, harmonisation, knowledge sharing in:
1. Assay development
2. Clinical validation
www.biomarkerdevelopmentcenter.nl
NL Grant 4.3M Eur (2014)
EU Grant 1M Eur (2016)
33 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
BDC is part of:
The Good Biomarker Practice initiative
Join forces among Europe’s major academic infrastructures + industry to:
1. Establish “Good Biomarker Practice” guidelines
- on translational research, biomarker technologies, biobanking, data stewardship.
2. Efficiently execute high quality biomarker projects
- work together in clinical validation and development of probable biomarkers.
{Nature Reviews Drug Discovery, accepted}34 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
Introducing 5 infrastructure communities
(local) (European)
(Netherlands)
35 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
Rich history of PPP in the Netherlands
(Centre for Translational Molecular Medicine) (Top Institute Pharma)
(BioMolecular Materials)
Public-private collaboration on diagnosis, drugs, devices (2006-2015)
36 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
>100 EXPERT GROUPS INVOLVED SO FAR
Nijmegen
Amsterdam
Wageningen
Utrecht
Rotterdam
Eindhoven
Maastricht
Groningen
Leiden
Delft
Enschede
Zeist
Hanze University
University Groningen
UMCG
Hubrecht Institute
UMCU
Utrecht University
Wageningen UR
PRI
TU Twente
Radboudumc
Radboud University
Maastricht Univ.
MUMC+
CTMM
TUe
ErasmusMC
Generade
LUMC
Leiden University
Naturalis
TUDelft
AMC
AMOLF
CWI
NLeSC
NKI
SURFSARA
University of Amsterdam
VU University Amsterdam
VUMC
TNO
20
17
44
13 115
6
4
5
1
9Technology & data
hotels
Access to high-tech
expertise & facilities
Wetlab & data facilities
Collections of
biosamples/cohorts
Public and private labs
Training & education
High-quality
experimental design
measuring
data stewardship
39 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
FOCUS ON CRITICAL COMPONENT: THE DATA
{Wilkinson et al, Nature Scientific Data, 2016}
Prof Barend Mons
Leiden University Medical Center
Dutch Techcenter for Life Sciences
Netherlands eScience Center
Data capture
Data stewardship (FAIR)
40 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
DATA STEWARDSHIP: INTEROPERABILITY IS KEY
If data are interoperable Data analytics provide new knowledge
41 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
ELIXIR-NL Areas
Data interoperability
Data stewardship
e-Infrastructure services
FAIR data training &
education
Cross-RI collaboration
BBMRI-NL
EATRIS-NL
NL-Bioimaging
e-Infra’s
Industry involvement
ELIXIR links FAIR data
…
Expertise
Resources
(databases)
Compute &
storage
Tools
Standards
Training
NL-NODE IN ELIXIR (‘DATA FOR LIFE’)
Technologies
Data
Learning
42 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
FAIR EVOLVING RAPIDLY INTO A GLOBAL MOVEMENT
Rapid acceptance and endorsement process
The conference
The Website
Research Data Alliance endorsement
DTL flagship project
FORCE11 international partner
Articles accepted in NATURE
NIH accepts FAIR compliance in Life Sciences Commons
DTL Data lead Prof. Barend Mons Chair High Level Expert Group EC
The Personal Health Train Initiative started
EC announces European Open Science Cloud with FAIR as leading principle
World 2017
43 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
ALSO THE G20 HAS RECENTLY ADOPTED FAIR!
“We support appropriate efforts to promote open science and facilitate
appropriate access to publicly funded research results on findable, accessible,
interoperable and reusable (FAIR) principles.” (Statement 12)
http://europa.eu/rapid/press-release_STATEMENT-16-2967_en.htm
44 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
Further joining forces in NetherlandsTo drive personalized medicine & health research
46 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
See Youtube – Health-RI
47 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017
Acknowledgements
Hans Wessels Jolein Gloerich
Roel Tans Esther Willems
Maurice van Dael Jenneke Keizer
Dirk Lefeber Monique van
Scherpenzeel
Leo Kluijtmans Ron Wevers
Marcel Verbeek Lucien Engelen
Jan Kremer Bas Bloem
Nathalie Bovy Paul Smits
the Radboudumc Technology Centers
and many others
www.radboudumc.nl/personalizedhealthcare
www.radboudumc.nl/research/technologycenters
www.radboudresearchfacilities.nl
www.linkedIn.com
www.slideshare.net/alainvangool
Many collaborators and funders
Jan van der Greef Ben van Ommen
Ivana Bobeldijk Hans Princen
Lars Verschuren Marjan van Erk
Suzan Wopereis Heleen Wortelboer
Wessel Kraaij Ronald Mooi
Peter van Dijken Cyrille Krul
and many others
CarTarDis
Ruben Kok Barend Mons
Jaap Heringa Merlijn van Rijswijk
and many others
Anton Ussi Florence Bietrix
Laura Bermejo Andreas Scherer
Sulev Koks Marian Hajduch
Giovanni Migliaccio
and many others
49 Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017