2017 02-22 Oxford Global Biomarker Congress, Manchester, Alain van Gool

Infrastructures for personalized medicine
and health research
Prof Alain van Gool

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 Healthcare
Head 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 Healthcare
Head 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]

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 !?

Serum N-glycopeptide profiling as biomarker discovery
Comprehensive QC analytics

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

8
New data !
(generators, owners)

Exciting next steps: translate laboratory to society
• Point-of-care analysis of
few biomarkers
• 1.000.000 signals per
proteomics analysis

implementation
innovation
research

Irreproducibility of data
{Freedman et al, PLOS Biology, 2015}
{2012} {2011} {2013} {2008}{2012}

Categories of errors leading to irreproducibility
{Freedman et al,
PLOS Biology, 2015}

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

Biomarker innovation gaps: some numbers
~ 5 biomarkers/
working day
1 biomarker/
1-3 years
1 biomarker/
2-10 years
Eg Biomarkers in time: Prostate cancer
May 2011: 2,231 biomarkers
Nov 2012: 6,562 biomarkers
Oct 2013: 8,358 biomarkers
Oct 2015: 11,856 biomarkers
Discovery Clinical
validation/confirmation
Diagnostic
test
Number of
biomarkers
Gap 1
Gap 2

Choice for biomarker scientists: discover or confirm?

Biomarkers for personalized medicine
and health
time for quality, not quantity

Way forward
Quote Freedman paper:
{Freedman et al, PLOS Biology, 2015}

Introducing 5 infrastructure communities
(local) (European)
(Netherlands)

www.radboudumc.nl/research/technologycenters
Genomics
Bioinformatics
Animal
studies
Stem
cells
Translational
neuroscience
Image-guided
treatment
Imaging
Microscopy
Biobank
Health
economics
Mass
Spectrometry
Radboudumc
Technology
Centers
Investigational
products
Clinical
studies
EHR data
analysis
Statistics
Human
performance
Data
stewardship
Molecule
Flow
cytometry
3D lab
21

About 280 dedicated people working in 19 Technology Centers, ~1800 users (internal, external), ~150 consortia
www.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
diagnostic
s
• iPSC
• Organoids
• 3D imaging
• 3D printing
• Virtual reality

Link to European infrastructures

24EATRIS15/02/2017
Filling the gaps (1)
GAP 1
Public increasingly funding early development, funding gap remains
Public Funding
Private Funding
Moves 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 2
Outputs of publicly funded projects misaligned with privately financed requirements
for further development
Public Funding
Technology push, publications
Private Funding
Product and patient focus, market pull
Fundamental
discovery
Early
Translational
F.I.M
Phase 1 Phase 2 Phase 3
GAP 2

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

27EATRIS15/02/2017
Client
projects
Infrastructure
Funding Expertise
GMP manufacturing
Licenses
Imaging facilities
Biobanks
Clinical trial units
Patient groups
Academia
Research /charities
SME/biotech
Pharma
Clinicians
Latest technologies
Project management
Regulatory
Partnering
Nat’l governments
Regional dev. Funds
H2020
Venture capital
Pharma partnering
Landscape
5 Technology Platforms

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

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

30EATRIS15/02/2017
TRANSLATIONAL MEDICINE’17, September 24 – 26, Prague
www.eatris.eu

(local) (European)
(Netherlands)

Ongoing independent biomarker activities
Europe
USA
{Asadullah et al, Nature Reviews Drug Discovery, Dec 2015}

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)
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

(local) (European)
(Netherlands)

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)

PARTNERSHIP FOR DATA, TECHNOLOGIES & LEARNING

DUTCH TECHCENTER FOR LIFE SCIENCES
NL platform enabling cross-disciplinary research

>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 1
15
6
4
5
1
9
Technology & 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

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)

DATA STEWARDSHIP: INTEROPERABILITY IS KEY
If data are interoperable Data analytics provide new knowledge

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

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

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

Further joining forces in Netherlands
To drive personalized medicine & health research

See Youtube – Health-RI

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
alain.vangool@tno.nl
alain.vangool@radboudumc.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

2017 02-22 Oxford Global Biomarker Congress, Manchester, Alain van Gool

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2017 02-22 Oxford Global Biomarker Congress, Manchester, Alain van Gool