The Idea - akademien-schweiz.ch · The Idea – Organism = Computer Life is the translation of the...
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The Idea – Organism = Computer
Life is the translation of the information in the genome into the phenotype of the organism:
The organism ‚computes‘ this phenotype from its genotype, given a specific environment (PentiumV) (neuronal net visualisation)
Genome
Phenotype
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The Problem – And It Is Not Getting Better
Global Cancer Burden
1. World wide ~12 million new cancer cases/year
2. Cure rates for most common forms of cancer have hardly changed over the last decades
3. Even the most advanced targeted therapies are typically only effective for a small fraction of the patients
4. Pharma development costs have dramatically increased, while the number of new drugs keeps dropping
Boyle and Levin, 2009
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The future of medicine and healthcare will be dictated by demographic change
Global prevalence of diabetes and impaired glucose tolerance (IGT) in 2010 and 2030
International Diabetes Association, 2010
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Colon Cancer
Zalcberg et al, NEJM 2008
(K-ras wild type)
SURV I VA L
Time in months
Many colon cancer patients with tumors without K-ras wild type will respond positively to treatment with EGFR receptor anatagonists
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Mutated K-ras
SURV I VA L
Time in months Zalcberg et al, NEJM 2008
Patients with tumors with K-ras mutations do not: a 30000 Euro treatment will show no effect on the tumor (but will cause significant side effects on the patient)
Colon Cancer
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Der Anfang: 1973
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30th September 2010, Brussel
Publica7on of Dra< Version
Interna7onal Human Genome Consor7um
Celera
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Change of technology in sequencing
1.2 billion DNA sequenzes in parallel 96 DNA sequenzes inparallel
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The Sequencing Explosion
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Large-scale international research collaborations relevant to ITFoM
ICGC comprehensive description of genomic, transcriptomic and epigenomic changes in 50 different tumor types
IHEC production of reference maps of at least 1000 epigenomes for key cellular states relevant to health and disease
IHMC International Human Microbiome Consortium explores the role of the human microbiome in the maintenance of health and causation of disease
1000 Genomes Project provides a comprehensive resource on human genetic variation
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• automobile crash tests entirely by computer simulation.
• These days >> at least 3 to 5 million equations.
• Computer simulations tobe safer than actual prototype car crash tests, because actual crash tests cannot simulate every possible situation. Robert Lange, General Motors executive director for vehicle structure and safety integration
• (from : Car crash tests and Computer Simulations, Michael Pines,
• http://seriousaccidents.com/blog/car-technology-accident-blog/car-crash-tests-and-computer-simulation/)
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Still An Insatiable Need For Computing
PetaFlop Systems of Today Are The Client And Handheld Systems 10 years Later
10 PFlops 1 PFlops
100 TFlops 10 TFlops 1 TFlops
100 GFlops 10 GFlops 1 GFlops
100 MFlops
100 PFlops
10 EFlops 1 EFlops
100 EFlops
1993 2017 1999 2005 2011 2023
1 ZFlops
2029
Weather Prediction
Medical Imaging
Genomics Research
Source: www.top500.org
Forecast
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Though barometers were increasingly in circulation since 1670, it wasn't until about 1860 that a famous English sea captain, Admiral Fitzroy, former Captain of Darwin's exploration ship "the Beagle", provided a detailed weather forecasting script that he attached to his several barometer inventions. Fitzroy is credited with the beginning of the first published weather forecasting in the world and detailing the meaning behind the rise and fall of air pressure. The English, and later the French, were the first to recognize the importance of these instruments, and in fact England's Board of Trade required large stick barometers, (3 for sale on this site), at all sea coastal towns so the sailors could view them before departing on a voyage.
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The Cancer Model – Knowledge Of Decades Of Research
Hanahan & Weinberg, 2011
Over 30 different signaling pathways are integrated: Cytokine signaling (e.g. CSF, IFNA, IL8), Death receptor signaling (e.g. Fas, TNFa, TRAIL), DNA repair / cell cycle, Ephrin signaling, GCPR/Hormone signaling (e.g. Glucagon, Insulin, Testosterone), Hedgehog signaling, Notch signaling, several RTK signaling (e.g. bNGF, EGF, FGF, IGF, PDGF, VEGF), TGFb signaling (e.g. BMP, TGFb) and Wnt signaling.
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TREAT20 – Treatment Of Malignant Melanoma Experimental Setup
20 metastatic melanoma cancer patients (10 cutaneous + 10 uveal)
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1. Expression data (high-throughput RNA sequencing) of melanocytes
2. Expression data (high-throughput RNA sequencing) of 9 tumors so far
3. Mutation data (high-throughput exome sequencing) of 9 tumors so far
TREAT20 – Current State
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TREAT20 – Molecular Analysis of Tumors
Ploidy of Tumor Cells
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TREAT20 – Patient Specific Modeling
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TREAT20 – Predicting Drug Response
c-Myc levels as a surrogate marker for clinical effectiveness
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TREAT20 – Chemosensitivity of Tumor Xenografts
Various Components
Patient1
Patient2
Patient3
Patient4
Patient5
Patient6
Patient7
Patient8
Patient9
EpCAM act. GLI
act. STAT3
nucl. ßCat
act. Casp pAKT
act. Ras pMEK
log2-ratio
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TREAT20 – Combinatorial Treatment
Various Components
Patient1
Patient2
Patient3
Patient4
Patient5
Patient6
Patient7
Patient8
Patient9
EpCAM act. GLI
act. STAT3
nucl. ßCat
act. Casp pAKT
act. Ras pMEK
log2-ratio
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FET Flagship Initiatives Concept
FET-F initiatives are:
• proposed to be visionary research initiatives building on areas of established European excellence and oriented towards a unifying goal via a FET-nucleated multidisciplinary approach
• proposed to generate waves of technological innovationand economic exploitation, ideally in a variety of areas and sectors, and would carry an important societal impact
• envisioned to run for at least 10 years, on a budget in the range of 100 M€ Euros per year and per initiative
• envisioned to be of such magnitude that they can only be realised through a federated effort of the different EC programmes, along with Member States, funding agencies and, where appropriate, global partners and industry
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Goal: Construction of integrated molecular/physiologica/anatomical models
for all participants in the healthcare system: from baby to old age, on the basis of -omics,
imaging and sensor data
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The Virtual Patient-Integration Of different Models
Molecules
Tissues Anatomy
Statistics
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Pat1 Pat1 data
Pat1 model
Reference-model
Pat2 Pat2 data
Pat2 model
Pat3 Pat3 data
Pat3 model
Pat4 Pat4 data
Pat4 model
Pat5 Pat5 data
Pat5 model
Pat6 Pat6 data
Pat6 model
Pat7 Pat7 data
Pat7 model
Pat8 Pat8 data
Pat8 model
Pat9 Pat9 data
Pat9 model
Pat10 Pat10 data
Pat10 model
Pat11 Pat11 data
Pat11 model
Pat12 Pat12 data
Pat12 model
Pat13 Pat14 data
Pat14 model
Pat15 Pat15 data
Pat15 model
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12 million new cancer cases per year: 1 genome per second
Modelling every patient at reasonable detail (1000 cell types, 1000 conditions, 1000 MC runs):
app. 1 billion core hours, 1 IBM BlueGeneL for 1 year per patient: energy cost limited medicine?
Reverse engineering of networks with thousands of components:
Unsolved!!!
........
.........
ICT challenges in an ICT driven medicine
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12 million new cancer cases per year: 1 genome per second
Modelling every patient at reasonable detail (1000 cell types, 1000 conditions, 1000 MC runs):
500 million Europeans, modelled 2 times a year:
~10**14 core years
900000 servers (Google) use app. 0.01% of world wide electricity
If we assume, every Google server has 100?? cores, we would still use 100 times the world wide electricity production to model every European
2 x a year
everse engineering of networks with thousands of components:
Unsolved!!!
........
.........
Why is this an ICT challenge?
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Technology resulting from our research at Stanford, Bell Labs, and Imperial College
One result per clock cycle
MAXELER DATAFLOW COMPUTING
Dynamic (switching) Power Consump7on:
Minimal frequency f achieves maximal performance, thus for a given power budget, we get Maximum Performance Compu7ng (MPC)!
31
fVCP DDloadavg ⋅⋅= 2
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Relations to EU Infrastructures
Integrated Structural Biology Infrastructure
European Sequencing and Genotyping Infrastructure
ISBE
Infrastructure for Systems Biology – Europe
Partnership for Advanced Computing in Europe
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ITFoM Partners and Associate Partners
- University of Auckland, New Zealand (P. Hunter) - Ontario Institute for Cancer Research, Canada (T. Hudson) - Institute for the Digital Economy, University of New Brunswick, Canada (M. Ulieru) - Institute for Quantum Computing, University
of Waterloo, Canada (D. Cory) - McGill University and Genome Quebec Innovation Centre, Canada(T. Nilsson) - Harvard Medical School, US (G. Church) - UCLA Wireless Health Institute, US (M. Sarrafzadeh) - University of California, Berkeley, US(S. Russel) - Institute for Systems Biology, Seattle, US (L. Hood) - Genome Sciences Centre, BC Cancer Agency (S.Jones) - Prior Knowledge - Complete Genomics - Hussmann Institute for Human Genomics - American University Beirut
99 Partners from Europe and beyond
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The ITFoM-Consortium Full Partners Associate Partners Max Planck Institute for Molecular Genetics (DE)
Eidgenössische Technische Hochschule Zürich (CH) University of Ostrava (CZ) Karolinska Institutet
Medical University of Graz (AT) Ontario Institute for Cancer Research (CA) TU Vienna (AT) University of Ljubljana
University College London (UK) International Foundation for Computer Assisted Radiology and Surgery (DE) Institut Pasteur (FR) University of Glasgow
VU University Amsterdam (NL) German Cancer Research Center (DE) HealthSolve (UK) University of Twente-CTIT
University of Manchester (UK) COSBI - Microsoft Corporation (US) CertiCon a.s. (CZ) European Molecular Biology Laboratory
European Molecular Biology Laboratory - IBM Research (CH) Czech Technical University in Prague (CZ) MPI of Colloids and Interfaces
European Bioinformatics Institute (DE/UK) Roche Diagnostics (DE) Dublin City University (IE) Graz University of Technology
Wellcome Trust Sanger Institute (UK) Agilent Technologies, Inc. (UK) Athens University of Economics and Business
(GR) Imec
KTH Royal Institute of Technology (SE) Life Technologies Corp./Visigene (US) SIVECO Romania (RO) Hussman Institute for Human Genomics
Imperial College London (UK) Bruker Daltonics GmbH (DE) University of Klagenfurt (AT) Max Delbrück Center for Molecular Medicine
Maastricht University (NL) AB SCIEX GmbH (DE) University of Strathclyde (UK) Bull Center for Magnetic Resonance (IT) Intel Deutschland GmbH (DE) Aalto University (FI) Meganexus International Prevention Research Institute (FR) Oxford Nanopore Technologies (UK) UCD Systems Biology Ireland (IE) American University of Beirut
Uppsala University (SE) Bayer Schering Pharma (DE) University of Copenhagen (DK) Alfréd Rényi Institute of Mathematics, Hungarian Academy of Sciences
University of Luxembourg (LU) Janssen Pharmaceutica (BE) University of Edinburgh (UK) SAP
University of Leicester (UK) Institute for the Digital Economy (CA) University of Rijeka (HR) Universidad Politecnica de Madrid
ISC Intelligence in Science (BE) Harvard Medical School (US) University of Waterloo- Institute for Quantum Computing Maxeler Technologies
University of Auckland (NZ) Dahlem Centre for Genome Research and Medical Systems Biology (DE) University of Rijeka University of Sheffield
Université de Genève (CH) Tel Aviv University (IL) IST Complete Genomics Inc
Centro Nacional de Análisis Genómico (ES)
XEROX Research Centre Europe (FR) TNO Health Level Seven International
Foundation
Siemens AG Österreich (AT) Oracle (DE) KU Leuven prior Knowledge Inc
Alacris Theranostics GmbH (DE) University of Genoa (IT) Donders Center for Neuroscience University of Iceland Charité - Universitätsmedizin Berlin (DE)
Estonian Genome Center of the University of Tartu (EE) Genome Sciences Centre, BC Cancer Agency. Global Helix LLC
Illumina Cambridge (UK) Max Planck Institute for Molecular Plant Physiology (DE) Jozef Stefan Institute Sabanci University
Commissariat à l‘Energie Atomique et aux Energies Alternatives - Metanomics Health GmbH (DE) Fraunhofer Institute for Biomedical Engineering
Centre national de Génotypage (FR)
Westfälische Wilhelms-Universität Münster (DE) FUJITSU LABORATORIES OF EUROPE LIMITED
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ITFoM Consortium
35
Countries Partners Associate Partners In Negotiation Austria MUG, Siemens VUT, AAU, TUG Belgium ISC Janssen, KUL, imec, HL7
Canada OICR, IMPACT, UW-IQC, BCGSC
Croatia UNIRI Czech Republic VSB, CertiCon, CTU, Denmark UNICO Estonia UT Finland HIIT France iPRI, CEA-CNG Xerox, Institut Pasteur, Bull
Germany MPIMG,Alacris, Charité
IFCARS, DKFZ, Roche, Bruker, ABSCiex, Intel, Life Technologies, Bayer, DZ-GFMSB, Oracle, MPIMPP, WWUM, MTNX, IBMT, EMBL, MPIKG. Mdc, SAP, Maxeler MD
Greece AUEB Hungary Renyi Iceland UICE Ireland DCU, UCD-SBI Israel TAU Italy CERM Microsoft, DIBE, IST Libanon AUB Luxembourg UL New Zealand UOA Romania SIVECO Slovakia MMC-SAV Slovenia JSI, UNILJ Spain CNAG UPM Sweden UU, KTH, Karolinska, Switzerland UNIGE ETH, IBM The Netherlands VUA, UM, TNO, DCN, CTIT Turkey USAB
United Kingdom UCL, ULEIC, UNIMAN, Illumina, EMBL-EBI, Sanger, Imperial
Agilent, Oxford Nanopore, Healthsolve, UNISTR, UEDIN, Fujitsu LE, UNIGL, Meganexus, UNISH
USA Harvard, HIHG, CG, prior, GH
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ITFoM Consortium
18 EC Member States included: Missing: Bulgaria, Cyprus, Latvia, Lithuania, Malta,
Poland, Portugal, EC Associated Countries included: Switzerland, Israel, Croatia, Turkey International Countries included: New Zealand, Canada, US, Libanon 75 Associate Partners from 25 countries
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“NEW YORK, Dec. 8, 2010 /PRNewswire/ -- Spending on healthcareamong theOECD (i) countries and BRIC nations of Brazil, Russia, India and China will grow by 51 percent between 2010 and 2020, amounting to a cumulative total of more than $71 trillion, according to estimates from PwC's Health Research Institute. Health spending in these areas is rising faster than gross domestic product, magnifying gaps in budget deficits and spurring governments to look to the private sector for ways to get a better value for taxpayers' money.”
“WorldwideIT Spending outperformed expectations in 2010, reaching $1.5 Trillion”, according to IDC's Worldwide Black Book from February 09, 2011 08:03 AM Eastern Time
Market
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Both ethically and economically, we can no longer afford the ineffective, cost- and
personnel intensive medicine of the past:
IT Future of Medicine
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For more information: Website: http://www.itfom.eu Email: [email protected] Twitter: @itfom Facebook: I.T. Future of Medicine LinkedIn: IT Future of Medicine
The project outcomes will enable the prediction of health, disease, therapy and its effects for individual patients and through application in the clinic will change the future of medicine.
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Thank you!