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Closing session - Hans V. Westerhoff

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SYSTEMS BIOLOGY AND SYSTEMS MEDICINE: TOWARDS A PRECISION MEDICINE September 26-30, 2016

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Closing session - Hans V. Westerhoff

  1. 1. Como Systems Medicine course 30/09/2016 Westerhoff et al: closure Page 1 The menu Systems Medicine  Flashes CaSyM form And now … Questions for YOU. Again, the same three groups discuss, come to a conclusion  and present: Marco 1. Given that several diseases depend on cell types and/or dynamically evolving sub‐ populations, what contribution could whole‐cell models give to precision  medicine? 2. Digital (whole‐cell/multi‐cell computational models) versus  mouse avatars  (xenopatients) in personalized medicine: which is the one to focus on and why? Matteo 1. Which are possible ways to integrate the various layers of cellular regulation (i.e.,  signaling, cell cycle, metabolism, gene regulation)? 2. When integrating regulatory layers, which constraints – if any – should one  implement in order for the integration process to be as close as possible to the real  cell behavior? The menu Systems Medicine  Flashes CaSyM form The menu Systems Medicine  Flashes CaSyM form The menu Systems Medicine  Flashes CaSyM form Closing session
  2. 2. Como Systems Medicine course 30/09/2016 Westerhoff et al: closure Page 2 CASYM form https://goo.g1/forms/N3gueOTdERovm PU43 or http://bit.ly/2cqUsxw Prepare to vote TXT 1 2 Text to +316 4250 0030 Type Wff <space> your choice (e.g. Wff b) Internet 1 2 Go to shakeq.com Log in with Wff International rates may apply This presentation has been loaded without the Shakespeak add-in. Want to download the add-in for free? Go to http://shakespeak.com/en/free-download/. I would like to have hands-on tutorials A. Yes B. No The question will open when you start your session and slideshow. Internet Go to shakeq.com and log in with Wff TXT Send to +316 4250 0030: Wff <space> your choice (e.g. Wff b) # Votes: 0 Closed I would like to have hands-on tutorials A. B. Yes No 50.0% 100.0% Internet Go to shakeq.com and log in with Wff TXT Send to +316 4250 0030: Wff <space> your choice (e.g. Wff b) Closed We will set these example results to zero once you've started your session and your slide show. In the meantime, feel free to change the looks of your results (e.g. the colors). It should be a good idea to focus the school on one disease (e.g. the systems biology of cancer) A. Yes B. No The question will open when you start your session and slideshow. Internet Go to shakeq.com and log in with Wff TXT Send to +316 4250 0030: Wff <space> your choice (e.g. Wff b) # Votes: 0 Closed It should be a good idea to focus the school on one disease (e.g. the systems biology of cancer) A. B. Yes No 50.0% 100.0% Internet Go to shakeq.com and log in with Wff TXT Send to +316 4250 0030: Wff <space> your choice (e.g. Wff b) Closed We will set these example results to zero once you've started your session and your slide show. In the meantime, feel free to change the looks of your results (e.g. the colors).
  3. 3. Como Systems Medicine course 30/09/2016 Westerhoff et al: closure Page 3 Should this focus be effected, then I would prefer the topic to be A. Cancer B. Metabolic Syndrome (=diabetes, obesity etc) C. Heart disease D. Inborn errors of metabolism E. Infectious disease F. Immune diseases inclusive of allergies The question will open when you start your session and slideshow. Internet Go to shakeq.com and log in with Wff TXT Send to +316 4250 0030: Wff <space> your choice (e.g. Wff b) # Votes: 0 Closed Should this focus be effected, then I would prefer the topic to be Internet Go to shakeq.com and log in with Wff TXT Send to +316 4250 0030: Wff <space> your choice (e.g. Wff b) Closed A. B. C. D. E. F. Cancer Metabolic Syndrome  (=diabetes, obesity etc) Heart disease Inborn errors of  metabolism Infectious disease Immune diseases inclusive  of allergies 16.7% 33.3% 50.0% 66.7% 83.3% 100.0% We will set these example results to zero once you've started your session and your slide show. In the meantime, feel free to change the looks of your results (e.g. the colors). A good registration fee for the school should be A. <200 euro; 1 foreign speaker B. 200< < 400 euro; 4 foreign speakers C. 400 < < 600 euro: 10 foreign speakers The question will open when you start your session and slideshow. Internet Go to shakeq.com and log in with Wff TXT Send to +316 4250 0030: Wff <space> your choice (e.g. Wff b) # Votes: 0 Closed A good registration fee for the school should be A. B. C. <200 euro; 1  foreign speaker 200<     < 400  euro; 4 foreign  speakers 400 <    < 600  euro: 10 foreign  speakers 33.3% 66.7% 100.0% Internet Go to shakeq.com and log in with Wff TXT Send to +316 4250 0030: Wff <space> your choice (e.g. Wff b) Closed We will set these example results to zero once you've started your session and your slide show. In the meantime, feel free to change the looks of your results (e.g. the colors). How many students/participants would you find optimal for a Como school of advanced studies? A. <30 B. 30 < < 60 C. 60< The question will open when you start your session and slideshow. Internet Go to shakeq.com and log in with Wff TXT Send to +316 4250 0030: Wff <space> your choice (e.g. Wff b) # Votes: 0 Closed How many students/participants would you find optimal for a Como school of advanced studies? A. B. C. <30 30 <   < 60 60< 33.3% 66.7% 100.0% Internet Go to shakeq.com and log in with Wff TXT Send to +316 4250 0030: Wff <space> your choice (e.g. Wff b) Closed We will set these example results to zero once you've started your session and your slide show. In the meantime, feel free to change the looks of your results (e.g. the colors).
  4. 4. Como Systems Medicine course 30/09/2016 Westerhoff et al: closure Page 4 I think a luxurious envirnment like this villa is great for the school (though expensive) A. Yes B. No The question will open when you start your session and slideshow. Internet Go to shakeq.com and log in with Wff TXT Send to +316 4250 0030: Wff <space> your choice (e.g. Wff b) # Votes: 0 Closed I think a luxurious envirnment like this villa is great for the school (though expensive) A. B. Yes No 50.0% 100.0% Internet Go to shakeq.com and log in with Wff TXT Send to +316 4250 0030: Wff <space> your choice (e.g. Wff b) Closed We will set these example results to zero once you've started your session and your slide show. In the meantime, feel free to change the looks of your results (e.g. the colors). What did we learn? In a nutshell The menu Systems Medicine  Flashes CaSyM form Hans Westerhoff:  Towards Precision Biology and Medicine • The Future in 2000 – What remained to be discovered • Life at the edge and the origin of Life – How to get your Carbon and Gibbs energy precisely (‐‐> Thierry Mondeel) • Towards precision medicine – Individualized medicine from PKU to Parkinson’s? (Alexey Kolodkin) – Transcription dynamics, cell‐cell heterogeneity and cancer ( Stefania Astrologo) – How understanding might matter: the Janus head of acute and chronic  inflammation • Serving the community  – Infrastructure systems Biology Europe (ISBE@NL): make me a model coalition  (Alexey Kolodkin) – Replica models, virtual human How can the metabolic map lead to new understanding of disease? A. Phenylketonuria leads to lack of brain development because of lack of tyr import into brain and because tyr is required for dopamine synthesis B. Because phenylalanine increases and is metabolized to the toxic phenylketone that is secreted into the urine C. Because lack of the enzyme phenylalanine hydroxylase causes a reduced flux down that pathway and a reduced synthesis of fumarate The question will open when you start your session and slideshow. Internet Go to shakeq.com and log in with Wff TXT Send to +316 4250 0030: Wff <space> your choice (e.g. Wff b) # Votes: 0 Closed
  5. 5. Como Systems Medicine course 30/09/2016 Westerhoff et al: closure Page 5 How can the metabolic map lead to new understanding of disease? Closed A. B. C. Phenylketonuria leads to lack of brain  development because of lack of tyr... Because phenylalanine increases and is  metabolized to the toxic... Because lack of the enzyme phenylalanine  hydroxylase causes a reduced flux... 33.3% 66.7% 100.0% We will set these example results to zero once you've started your session and your slide show. In the meantime, feel free to change the looks of your results (e.g. the colors). Why is multifactorial disease complex in more than two ways? A. Because 26 000 genes are involved B. It requires multiple factors to be altered, which can be remote, and not always the same factors, and differing between individuals C. Because there are so many (thousands) of metabolites The question will open when you start your session and slideshow. Internet Go to shakeq.com and log in with Wff TXT Send to +316 4250 0030: Wff <space> your choice (e.g. Wff b) # Votes: 0 Closed Why is multifactorial disease complex in more than two ways? Closed A. B. C. Because 26 000 genes are  involved It requires multiple factors to  be altered, which can be  remote, and not always the  same factors, and differing  between individuals Because there are so many  (thousands) of metabolites 33.3% 66.7% 100.0% We will set these example results to zero once you've started your session and your slide show. In the meantime, feel free to change the looks of your results (e.g. the colors). The menu Systems Medicine  Flashes CaSyM form Enzo Medico:  Towards Precision Biology and Medicine • Tumor heterogeneity • Individual progression of tumors • miRNA involved in regulation • It makes sense to hunt for exceptions: try to cure the outliers • Stromal involvement • Visualization of data for the physician – Replica models, virtual human mRNA signature of tumors is signature of A. cancer stem cells B. tissue stem cells The question will open when you start your session and slideshow. Internet Go to shakeq.com and log in with Wff TXT Send to +316 4250 0030: Wff <space> your choice (e.g. Wff b) # Votes: 0 Closed
  6. 6. Como Systems Medicine course 30/09/2016 Westerhoff et al: closure Page 6 mRNA signature of tumors is signature of A. B. cancer stem cells tissue stem cells 50.0% 100.0% Closed We will set these example results to zero once you've started your session and your slide show. In the meantime, feel free to change the looks of your results (e.g. the colors). The menu Systems Medicine  Flashes CaSyM form Giancarlo Mauri:  Towards Precision Biology and Medicine Reconstruction of cancer progression: As ensemble, or As individual cells How to figure out temporal sequence from random samples without  time stamp? – Replica models, virtual human What was an important assumption of the approach? A. Gene expression can be measured B. Features are acquired, never lost The question will open when you start your session and slideshow. Internet Go to shakeq.com and log in with Wff TXT Send to +316 4250 0030: Wff <space> your choice (e.g. Wff b) # Votes: 0 Closed What was an important assumption of the approach? A. B. Gene expression can be  measured Features are acquired,  never lost 50.0% 100.0% Closed We will set these example results to zero once you've started your session and your slide show. In the meantime, feel free to change the looks of your results (e.g. the colors). The menu Systems Medicine  Flashes CaSyM form
  7. 7. Como Systems Medicine course 30/09/2016 Westerhoff et al: closure Page 7 Thierry Mondeel :  Towards Precision Biology and Medicine • How to map out fluxes on a genome wide map • Precise specification of modelling methodology required for  reproducible science • Various combinations of redox enzymes lead to various ATP/acetate  yields and biotechnology yields – Replica models, virtual human Unlike the experimental literature, the modelling literature is robust A. No B. Yes The question will open when you start your session and slideshow. Internet Go to shakeq.com and log in with Wff TXT Send to +316 4250 0030: Wff <space> your choice (e.g. Wff b) # Votes: 0 Closed Unlike the experimental literature, the modelling literature is robust A. B. No Yes 50.0% 100.0% Closed We will set these example results to zero once you've started your session and your slide show. In the meantime, feel free to change the looks of your results (e.g. the colors). The menu Systems Medicine  Flashes CaSyM form Sampsa Hautaniemi:  Towards Precision Biology and Medicine – Replica models, virtual human – Factors can be both pro‐ and anti apoptotic (e.g. JNK) – Resistance due to pre‐existing subpopulation – Pre‐target, on‐target, post‐target and off‐target  resistance – A model with on‐ and post‐target resistance that works Drug resistance of tumors is mostly due to the cells adapting to the drug. True or false? A. True B. False The question will open when you start your session and slideshow. Internet Go to shakeq.com and log in with Wff TXT Send to +316 4250 0030: Wff <space> your choice (e.g. Wff b) # Votes: 0 Closed
  8. 8. Como Systems Medicine course 30/09/2016 Westerhoff et al: closure Page 8 Drug resistance of tumors is mostly due to the cells adapting to the drug. True or false? A. B. True False 50.0% 100.0% Closed We will set these example results to zero once you've started your session and your slide show. In the meantime, feel free to change the looks of your results (e.g. the colors). The menu Systems Medicine  Flashes CaSyM form Damjana Rozman:  Towards Precision Biology and Medicine – Replica models, virtual human – CASYM – NAFLD – Strong effect of gender – Existing genome‐wide metabolic map (Hepatonet) not  suitable for pathology – NAFLD causing switch from: • gluconeogenesis from lactate to • gluconeogenesis from glycerol – STEATONET model – using connections of liver cells to other cells is crucial Is the time of day one determines cholesterol metabolism important? A. Yes B. No The question will open when you start your session and slideshow. Internet Go to shakeq.com and log in with Wff TXT Send to +316 4250 0030: Wff <space> your choice (e.g. Wff b) # Votes: 0 Closed Is the time of day one determines cholesterol metabolism important? A. B. Yes No 50.0% 100.0% Closed We will set these example results to zero once you've started your session and your slide show. In the meantime, feel free to change the looks of your results (e.g. the colors). The menu Systems Medicine  Flashes CaSyM form
  9. 9. Como Systems Medicine course 30/09/2016 Westerhoff et al: closure Page 9 Alexey Kolodkin:  Towards Precision Biology and Medicine – Replica models, virtual human – ISBE.NL: infrastructure; make‐me‐a‐model and  standards – MAPkinase pathway model – Parkinson’s disease model with four design principles  understood – Coffee helping against PD may be understood Why is a MAP kinase pathway not a MAP kinase pathway? A. It starts with Ras not MAP B. It would cause cancer if it was C. It is only determined by Ras attachment to the membrane; pathway is irrelevant The question will open when you start your session and slideshow. Internet Go to shakeq.com and log in with Wff TXT Send to +316 4250 0030: Wff <space> your choice (e.g. Wff b) # Votes: 0 Closed Why is a MAP kinase pathway not a MAP kinase pathway? Closed A. B. C. It starts with Ras not  MAP It would cause cancer if it  was It is only determined by  Ras attachment to the  membrane; pathway is  irrelevant 33.3% 66.7% 100.0% We will set these example results to zero once you've started your session and your slide show. In the meantime, feel free to change the looks of your results (e.g. the colors). The menu Systems Medicine  Flashes CaSyM form Walter Kolch:  Towards Precision Biology and Medicine – Replica models, virtual human – Euler (Königsbergen) first to show importance of  abstractions (models) – Adaptation important in determining drug response – Negative feedback amplifier: takes away drug effect – Unless drug affects the amplification itself – Only 30% of patients respond to a drug Which is the more promising approach for the future? A. Organoids B. Collecting all human information C. Xenografts The question will open when you start your session and slideshow. Internet Go to shakeq.com and log in with Wff TXT Send to +316 4250 0030: Wff <space> your choice (e.g. Wff b) # Votes: 0 Closed
  10. 10. Como Systems Medicine course 30/09/2016 Westerhoff et al: closure Page 10 Which is the more promising approach for the future? A. B. C. Organoids Collecting all  human  information Xenografts 33.3% 66.7% 100.0% Closed We will set these example results to zero once you've started your session and your slide show. In the meantime, feel free to change the looks of your results (e.g. the colors). The menu Systems Medicine  Flashes CaSyM form Gennaro Piccialli:  Towards Precision Biology and Medicine – Replica models, virtual human – Chemical drug design – Lipitor best selling drug: 14 billion$ – Most drugs promiscuous (7 targets) – Decorated nanoparticles Which disease was the first blockbuster drug for? A. Tuberculosis B. Spanish flue C. Syphillis The question will open when you start your session and slideshow. Internet Go to shakeq.com and log in with Wff TXT Send to +316 4250 0030: Wff <space> your choice (e.g. Wff b) # Votes: 0 Closed Which disease was the first blockbuster drug for? A. B. C. Tuberculosis Spanish flue Syphillis 33.3% 66.7% 100.0% Closed We will set these example results to zero once you've started your session and your slide show. In the meantime, feel free to change the looks of your results (e.g. the colors). The menu Systems Medicine  Flashes CaSyM form
  11. 11. Como Systems Medicine course 30/09/2016 Westerhoff et al: closure Page 11 Hans Lehrach:  Towards Precision Biology and Medicine – Replica models, virtual human – Broken arm as example of personalized medicine – Health care in Europe 1 Trillion €/year – Genome sequence, deep sequencing mRNA,  somatic  variants. – After training linear kinetic model: predictive success – Reverse engineering of parameters rather than Monte  Carlo approach – Pharma and personalized medicine: greatly reduced  attrition  rate will pay for it Why are European physicians against the use of virtual patient? A. Cannot get sued by patient for giving wrong, first-line treatment B. Better medical ethical code C. Because it is more expensive The question will open when you start your session and slideshow. Internet Go to shakeq.com and log in with Wff TXT Send to +316 4250 0030: Wff <space> your choice (e.g. Wff b) # Votes: 0 Closed Why are European physicians against the use of virtual patient? Closed A. B. C. Cannot get sued by  patient for giving  wrong, first‐line  treatment Better medical ethical  code Because it is more  expensive 33.3% 66.7% 100.0% We will set these example results to zero once you've started your session and your slide show. In the meantime, feel free to change the looks of your results (e.g. the colors). The menu Systems Medicine  Flashes CaSyM form Lilia Alberghina:  Towards Precision Biology and Medicine – Replica models, virtual human – K‐Ras effect on cancer is really due to uncoupling of gln and glucose metabolism – Cancer metabolic rewiring: due to limited, but non zero  oxygen; partical gln oxidation to lactate, glucose to  lactate – Branched anti‐TCA cycle Should primary approach to cancer target signalling, gene expression or metabolism? A. signalling B. transcription C. metabolism The question will open when you start your session and slideshow. Internet Go to shakeq.com and log in with Wff TXT Send to +316 4250 0030: Wff <space> your choice (e.g. Wff b) # Votes: 0 Closed
  12. 12. Como Systems Medicine course 30/09/2016 Westerhoff et al: closure Page 12 Should primary approach to cancer target signalling, gene expression or metabolism? A. B. C. signalling transcription metabolism 33.3% 66.7% 100.0% Closed We will set these example results to zero once you've started your session and your slide show. In the meantime, feel free to change the looks of your results (e.g. the colors). The menu Systems Medicine  Flashes CaSyM form Chiara Damiani:  Towards Precision Biology and Medicine – Replica models, virtual human – Flux balance analysis – ATP cost biomass due to fitting – Results depend on assumed maintenance – Sampling of solutions with random objective functions – Natural segregation into +/‐ Warburg, +/‐ growth  phenotypes Is growth rate the only objective to be considered? A. Yes, cancer cells outgrow others B. No, other solutions may arise because of drizzle of mutations The question will open when you start your session and slideshow. Internet Go to shakeq.com and log in with Wff TXT Send to +316 4250 0030: Wff <space> your choice (e.g. Wff b) # Votes: 0 Closed Is growth rate the only objective to be considered? Closed A. B. Yes, cancer cells  outgrow others No, other solutions  may arise because  of drizzle of  mutations 50.0% 100.0% We will set these example results to zero once you've started your session and your slide show. In the meantime, feel free to change the looks of your results (e.g. the colors). The menu Systems Medicine  Flashes CaSyM form
  13. 13. Como Systems Medicine course 30/09/2016 Westerhoff et al: closure Page 13 Matteo Barberis:  Towards Precision Biology and Medicine – Replica models, virtual human – Cyclins direct cyclin dependent kinases – Some with dual function Marco Vanoni:  Towards Precision Biology and Medicine – Replica models, virtual human – Computational model, versus – Avatars in mouse – Cell type important for disease Is a model of the human cell good enough to understand disease? A. Yes B. No The question will open when you start your session and slideshow. Internet Go to shakeq.com and log in with Wff TXT Send to +316 4250 0030: Wff <space> your choice (e.g. Wff b) # Votes: 0 Closed Is a model of the human cell good enough to understand disease? A. B. Yes No 50.0% 100.0% Closed We will set these example results to zero once you've started your session and your slide show. In the meantime, feel free to change the looks of your results (e.g. the colors). The menu Systems Medicine  Flashes CaSyM form Marco Viceconti:  Towards Precision Biology and Medicine – Replica models, virtual human – Bone and skeletal modelling possible – Multi‐scale modelling from hip to cell – Existing molecular data not good enough – Virtual Physiological Human  – VPH to the society
  14. 14. Como Systems Medicine course 30/09/2016 Westerhoff et al: closure Page 14 Is systems biology enough to understand disease? A. Yes, because drugs are molecules B. No, because all is decided at tissue level C. No, because it is also decided at tissue level The question will open when you start your session and slideshow. Internet Go to shakeq.com and log in with Wff TXT Send to +316 4250 0030: Wff <space> your choice (e.g. Wff b) # Votes: 0 Closed Is systems biology enough to understand disease? Closed A. B. C. Yes, because drugs are  molecules No, because all is decided at  tissue level No, because it is also decided  at tissue level 33.3% 66.7% 100.0% We will set these example results to zero once you've started your session and your slide show. In the meantime, feel free to change the looks of your results (e.g. the colors). The menu Systems Medicine  Flashes CaSyM form Anneke Koster:  Towards Precision Biology and Medicine – Replica models, virtual human – Forensics is developing like systems medicine – Much integration of heterogeneous data required – Learning from thousands of other cases (retrospective  data in repository) Each crime scene is different. Can they learn from each other? A. Yes, because criminals repeat themselves B. No, it is a can of worms (all different) C. Yes, because crimes can only be committed according to a limited set of models The question will open when you start your session and slideshow. Internet Go to shakeq.com and log in with Wff TXT Send to +316 4250 0030: Wff <space> your choice (e.g. Wff b) # Votes: 0 Closed Each crime scene is different. Can they learn from each other? Closed A. B. C. Yes, because criminals  repeat themselves No, it is a can of worms (all  different) Yes, because crimes can  only be committed  according to a limited set  of models 33.3% 66.7% 100.0% We will set these example results to zero once you've started your session and your slide show. In the meantime, feel free to change the looks of your results (e.g. the colors).
  15. 15. Como Systems Medicine course 30/09/2016 Westerhoff et al: closure Page 15 Thanks • The Alessandro Volta Foundation and Prof Giulio  Casati for generous support and the beautiful  accommodation • The centers (SysBio.IT) for support • Prof Alberghina: organization planning • Max: Organization • Speakers, tutors: tremendous effort in making  things debatable • You: active participation See you in  Stockholm, Como Or other places

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