Lecture on innovations in personalized healthcare using an integrated X-omics approach towards personalized diagnostics, as part of the regional ambitious TopFit program.
2019 06-19 Dutch association for clinical chemistry and laboratory medicine -...
2019 03-14 Health Valley Event 2019, Nijmegen, Alain van Gool
1. 1 One step ahead of disease and disease burden
2 Two more healthy life years
3 Three hubs: Food – Health - Tech
Innovatie in Personalized Healthcare
Prof Alain van Gool
Professor Personalized Healthcare
Head Translational Metabolic Laboratory
Coordinator Radboudumc Technology Centers
Lead PI Netherlands X-omics Initiative
2. Innovatie in Personalized Healthcare
Personalized diagnosis
Personalized therapy
= Personalized healthcare
+Patient participation
X-Omics
Therapy monitoring
2 Alain van Gool, Health Valley Event 2019, Nijmegen, 14 March 2019
3. Persoonsgerichte zorg in zeldzaam metabole ziekten
Normale Nederlandse ouders
Zoon Brian 2002, laag geboortegewicht, hoog lactaat, laag bloedsuiker
Mentale retardatie, bewegingsstoornis, epilepsie
† leeftijd 3,5 jr (ademhalingsfalen)
Zoon Joël 2009, hetzelfde klinisch beeld
† leeftijd 1,5 jr (epilepsie aanvallen)
Vermoeden van defect in mitochondriële functie
{Wortmann et al, Human Biology 2017}
Case studie
3 Alain van Gool, Health Valley Event 2019, Nijmegen, 14 March 2019
5. Nieuw ziekte mechanisme
• WARS2 is mtDNA-gecodeerd
tryptophanyl-tRNA synthases
• Nieuwe mutaties leiden tot
instabiliteit van WARS2 eiwit
• Minder Trp-tRNATrp
• Minder eiwit produktie
• New prenatal genetic test
{Wortmann et al, Human Biology 2017}
5 Alain van Gool, Health Valley Event 2019, Nijmegen, 14 March 2019
7. De kracht van omics in diagnostiek
Genomics
Test van 3.000.000.000 DNA basen
in 1 keer
500
1000
1500
2000
m/z
5 10 15 20 25 30 35 40 Time [min]
Proteomics, glycomics, metabolomics
Test van 10.000-50.000 eiwitten, glycanen
of metabolieten in 1 keer
7 Alain van Gool, Health Valley Event 2019, Nijmegen, 14 March 2019
8. De kracht van omics in diagnostiek
Enkele
biomarker
Omics
panel
Patient 1
Patient 2
• Grotere kans op positieve
diagnostiek
• Context van de verandering
↑ toename
↓ afname
8 Alain van Gool, Health Valley Event 2019, Nijmegen, 14 March 2019
9. Precision medicine in genetisch-metabole ziekten – nu
Persoonsgerichte diagnose
Genomics
(WES)
Metabolomics
Nieuwe ziekte
mechanismen
Persoonsgerichte therapie
Nature Genetics 2018
NEJM 2014
Nature 2016
NEJM 2014
Genet Med 2017
Glycomics
9 Alain van Gool, Health Valley Event 2019, Nijmegen, 14 March 2019
10. Precision medicine in genetisch-metabole ziekten – toekomst
Genomics
(WGS)
Metabolomics
Glycomics
Glycoproteomics
Deep Learning
Artificial Intelligence
System biology
Nature Genetics 2016 Pilot 2017
Persoonsgerichte diagnose Nieuwe ziekte
mechanismen
Persoonsgerichte therapie
10 Alain van Gool, Health Valley Event 2019, Nijmegen, 14 March 2019
11. Innovatie in Personalized Healthcare
Personalized diagnosis
Personalized therapy
= Personalized healthcare
+Patient participation
X-Omics
Therapy monitoring
11 Alain van Gool, Health Valley Event 2019, Nijmegen, 14 March 2019
Health
health
Citizen
Health
12. www.radboudumc.nl
• Snelle vertaling moleculair onderzoek naar diagnostiek
• Nieuwe ingangen voor persoonsgerichte therapie en
therapie monitoring
• Oproep naar partners voor gezamenlijke ontwikkeling
12 Alain van Gool, Health Valley Event 2019, Nijmegen, 14 March 2019
13. Acknowledgements
Translational Metabolic Laboratory
Hans Wessels
Dirk Lefeber
Karlien Coene
Leo Kluijtmans
Richard Rodenburg
Jolein Gloerich
Anouk Suppers
Purva Kulkarni
Roel Tans
Esther Willems
Ron Wevers
and others
Edwin Cuppen
Albert Heck
Thomas Hankemeier
Peter Bram ‘t Hoen
Daniella Kasteel
and others
Collaborators/funders
Human Genetics Nijmegen
Marcel Nelen
Alexander Hoischen
Lisenka Vissers
Christian Gillisen
Han Brunner
and others
alain.vangool@radboudumc.nl
www.radboudumc.nl/en/people/alain-van-gool
www.slideshare.net/alainvangool
CarTarDis
Daphna Habets
Arthur van den Wijngaard
and others
Rainer Bischoff
Theo Luider
and others