jacques fellay, epfl, pour la journée e-health 2013

From human genomic research

to digital medicine

Jacques Fellay

School of Life Sciences

EPFL – Lausanne, Switzerland

Marching towards predictive,

preventive, personalized and

participatory (4P) medicine

A revolution in the making

Eric Green et al., Charting a course for genomic medicine from base pairs to bedside, Nature 2011

A revolution in the making

2001: A Species' Odyssey

3 billions base pairs (ATGC) 23’000 protein-coding genes

99.9% inter-individual identity (yet 4 millions differences) 99% identical to chimpanzee genome (yet 6% different genes)

The human genome

DNA

RNA

Proteins

ATGC

AUGC

20 amino acids

The flow of genetic information

Epigenome

Metagenome

Proteome

Metabolome

Transcriptome

Exploring the human genome

Sanger sequencing,

targeted genotyping

Genome-wide

genotyping (GWAS)

Exome

sequencing

Genome

sequencing

2001 2008

We are all different…

4 million DNA variants / individual

Single nucleotide polymorphisms (SNPs)

Small insertions/deletions (indels)

Larger structural variants

• copy number variants (CNVs)

• inversions

• translocations

Exploiting human genetic variation

Identification of relevant genetic variant

Prediction models

Understanding of underlying biology

Clinically useful prediction

Clinically useful therapies

Infection

Exposure

Viral control -

disease

progression

Resistance -

acquisition

HIV host genetic studies:

clinical phenotypes

Science 1996 Sep 27;273(5283):1856-62

Science 2010 Dec 10;330(6010):1551-7

Science 2007 Aug 17;317(5840):944-7

Genetic score and HIV disease progression

Fellay et al., PLoS Pathogens 2011

IL28B genotype and response

to anti-hepatitis C treatment

Ge, Fellay et al. Nature 2009

0

18.7

48.4

0.8

10

0

10

20

30

40

50

60

CC n=18

AC n=252

AA n=1,010

Pe

rce

nta

ge

rs7270101

0 4.5

47.6

9.3

0

10

20

30

40

50

60

AA n=10

CA n=156

CC n=1,114

Pe

rce

nta

ge

rs1127354

Hb decline >3g/dL

Hb level <10g/dL ITPA-deficiency ITPA-deficiency

Fellay et al. Nature 2010

Hemoglobin drop, by ITPA genotypes and predicted function

ITPA genotype and anti-HCV

treatment-induced anemia

Who needs therapy? Will therapy be effective? When to start? Which drug regimen? For how long? Will therapy be tolerated?

The clinical management of patients suffering from chronic

hepatitis C virus infection represents an ideal setting to

demonstrate the relevance of personalized medicine

A. Rauch & J. Fellay

Phase 1b trials:

• Comparable efficacy to IFN-a

• Synergistic effect with IFN-a

• Less side effects

- tissue specific receptor expression

Interferon-lambda: a promising HCV drug

- It starts here and now

- It raises extremely broad issues

Across many fields: medicine, research, economy,

law, ethics, philosophy…

- It offers many avenues for job opportunities

Development of new industry focused on

nanotechnology, medical IT, digitalization,

biobanking, impact assessment, wellness, etc.

Personalized health

By fostering programs of basic & applied research in:

-Genetics, genomics, proteomics, metabolomics

-Integrative (“systems”) biology and medicine

-Bioinformatics / Biomathematics (data analysis)

-Computational biology / modeling / imaging

-Computer sciences (data management /encryption)

-Ethics, law and economics

Personalized health: how to get there?

Research

By training trans-disciplinary scientists, engineers and

medical doctors, for instance through the teaching of:

-“Medicine 101” for scientists and engineers

-Quantitative sciences and technology for medical

students

Personalized health: how to get there?

Education

Through the creation of funding mechanisms that allow

the creation, maintenance and staffing of state-of-the-art

“technolomics” R&D platforms, needed both for research

in “systems medicine” and for clinical applications.

Through an in-depth reflection on (targeted) biobanking.

Through discussion / collaboration between national

bodies in charge of health care and biomedical research.

Personalized health: how to get there?

Infrastructure

By educating the population and keeping it properly

informed about the potential, progress and limitations of

personalized health, allowing for a public debate of all relevant issues, and the exploitation of social networks

Personalized health: how to get there?

Social framework

PATIENT SOCIETY

Digital data

Health information

Clinical interface

Data generation

Data analysis Clinical translation

Privacy & Ethics

Education & Training

A virtual “Digital Medicine Campus”

in Western Switzerland?

More than 60 medical, research and advocacy organizations

in 41 countries formed a global alliance to share patients'

genetic and clinical information in an effort to "dramatically

accelerate medical progress" in determining the biological

bases of inherited and infectious diseases, as well as shed

light on the effects of various treatments on different patients.

Thank you!

http://fellay-lab.epfl.ch