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 HealthcareHead Radboud Center for Proteomics, Glycomics & Metabolomics Coordinator Radboud Technology Centers

Alain van Gool, Oxford Global Biomarkers Conference, Manchester, 21 Feb 2017

https://www.google.nl/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiLsvL0--jMAhWKWhQKHUFEBWMQjRwIBw&url=https://en.wikipedia.org/wiki/Leiden_University&bvm=bv.122448493,d.ZGg&psig=AFQjCNG2nD-SOcwwEdKmo9jecYe4fqRj-w&ust=1463844511999998

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

https://www.google.nl/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiLsvL0--jMAhWKWhQKHUFEBWMQjRwIBw&url=https://en.wikipedia.org/wiki/Leiden_University&bvm=bv.122448493,d.ZGg&psig=AFQjCNG2nD-SOcwwEdKmo9jecYe4fqRj-w&ust=1463844511999998

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



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 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


Choice for biomarker scientists: discover or confirm?


Biomarkers for personalized medicine and health

time for quality, not quantity


Way forwardQuote Freedman paper:



Introducing 5 infrastructure communities

(local) (European)

(Netherlands)


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


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


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 manufacturingLicensesImaging facilitiesBiobanksClinical trial unitsPatient groups

AcademiaResearch /charitiesSME/biotechPharma

CliniciansLatest technologiesProject managementRegulatoryPartnering

Nat’l governmentsRegional dev. FundsH2020Venture capitalPharma 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:

http://www.erasmusmc.nl/index.htm

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 SCIENCESNL 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

13 115

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


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 NetherlandsTo drive personalized medicine & health research


See Youtube – Health-RI


24-2-2017 48

http://www.alzheimer-nederland.nl/

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

[email protected]

[email protected]

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


http://www.erasmusmc.nl/index.htm

Health & Medicine

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