Skip to main content
SpringerLink
Log in

Anatomy and Physiology of Multiscale Modeling and Simulation in Systems Medicine

  • Protocol
Book cover Systems Medicine

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1386))

Abstract

Systems medicine is the application of systems biology concepts, methods, and tools to medical research and practice. It aims to integrate data and knowledge from different disciplines into biomedical models and simulations for the understanding, prevention, cure, and management of complex diseases. Complex diseases arise from the interactions among disease-influencing factors across multiple levels of biological organization from the environment to molecules. To tackle the enormous challenges posed by complex diseases, we need a modeling and simulation framework capable of capturing and integrating information originating from multiple spatiotemporal and organizational scales. Multiscale modeling and simulation in systems medicine is an emerging methodology and discipline that has already demonstrated its potential in becoming this framework. The aim of this chapter is to present some of the main concepts, requirements, and challenges of multiscale modeling and simulation in systems medicine.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Craig J (2008) Complex diseases: research and applications. Nat Educ 1(1):184

    Google Scholar 

  2. Bousquet J, Anto JM, Sterk PJ, Adock IM, Chung KF, Roca J et al (2011) Systems medicine and integrated care to combat chronic noncommunicable diseases. Genome Med 3(7):43

    Article  PubMed Central  PubMed  Google Scholar 

  3. Hood L, Friend SH (2012) Predictive, personalized, preventive, participatory (P4) cancer medicine. Nat Rev Clin Oncol 8(3):184–187

    Article  Google Scholar 

  4. Capobianco E (2012) Ten challenges for systems medicine. Front Genet 3(193):1–4

    Google Scholar 

  5. Calzolari D, Bruschi S, Coquin L, Schofield J, Feala JD, Reed JC, McCulloch AD, Paternostro G (2008) Search algorithms as a framework for the optimization of drug combinations. PLoS Comput Biol 4(12):e1000249

    Article  PubMed Central  PubMed  Google Scholar 

  6. Von Bertalanffy L (1969) General systems theory. Braziller, New York

    Google Scholar 

  7. Sloot PMA, Hoekstra AG (2010) Multi-scale modelling in computational biomedicine. Brief Bioinform 11(1):142–152

    Article  PubMed  Google Scholar 

  8. Hunter PJ, Borg TK (2003) Integration from proteins to organs: the Physiome Project. Nat Rev Mol Cell Biol 4:237–243

    Article  CAS  PubMed  Google Scholar 

  9. Hunter P, Nielsen P (2005) A strategy for integrative computational physiology. Physiology (Bethesda) 20(5):316–325

    Article  CAS  Google Scholar 

  10. Noble D (2002) Modeling the heart – from genes to cells to the whole organ. Science 295(5560):1678–1682

    Article  CAS  PubMed  Google Scholar 

  11. Dada JO, Mendes P (2011) Multi-scale modelling and simulation in systems biology. Integr Biol 2011(3):86–96

    Article  Google Scholar 

  12. Machado D, Costa RS, Rocha M, Ferreira EC, Tidor B, Rocha I (2011) Modeling formalisms in systems biology. AMB Express 1:45

    Article  PubMed Central  PubMed  Google Scholar 

  13. Hoops S, Sahle S, Gauges R, Lee C, Pahle J, Simus N, Singhal M, Xu L, Mendes P, Kummer U (2006) COPASI – a Complex Pathway Simulator. Bioinformatics 22(24):3067–3074

    Article  CAS  PubMed  Google Scholar 

  14. Bois FY (2009) GNU MCSim: Bayesian statistical inference for SBML-coded systems biology models. Bioinformatics 25(11):1453–1454

    Article  CAS  PubMed  Google Scholar 

  15. Adams R, Clark A, Yamaguchi A, Hanlon N, Tsorman B, Ali S, Lebedeva G, Goltsov A, Sorokin A, Akman OE, Troein C, Millar AJ, Goryanin I, Gilmore S (2013) SBSI: an extensible distributed software infrastructure for parameter estimation in systems biology. Bioinformatics 29(5):664–665

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Butterworth E, Jardine BE, Raymond GM, Neal ML, Bassingthwaighte JB (2014) JSim, an open-source modeling system for data analysis. F1000Res 2:288

    Google Scholar 

  17. Barlas Y (1994) Model validation in systems dynamics. Int’l systems dynamics conference, p 1–10

    Google Scholar 

  18. Chopard B, Borgdorff J, Hoekstra AG (2014) A framework for multi-scale modelling. Phil Trans R Soc A 372(2021):20130378

    Article  PubMed Central  PubMed  Google Scholar 

  19. Borgdorff J, Falcone J-L, Eric Lorenz E, Bona-Casas C, Chopard B, Hoekstra AG (2013) Foundations of distributed multiscale computing: Formalization, specification, and analysis. J Parallel Distrib Comput 73:465–483

    Article  Google Scholar 

  20. Borgdorff J, Mamonski M, Bosak B, Kurowski K, Ben Belgacem M, Chopard B, Groen D, Coveney PV, Hoekstra AG (2014) Distributed multiscale computing with MUSCLE 2, the multiscale coupling library and environment. J Comput Sci 2014(5):719–731

    Article  Google Scholar 

  21. Walker D, Southgate JS, Hill G, Holcombe M, Hose D, Wood S, MacNeil S, Smallwood R (2009) The epitheliome: modelling the social behavior of cells. Biosystems 76:89–100

    Article  Google Scholar 

  22. Noble D (2006) The music of life: biology beyond the genome. Oxford University Press, Oxford

    Google Scholar 

  23. An G, Mi Q, Dutta-Moscato J, Vodovotz Y (2009) Agent-based models in translational systems biology. Wiley Interdiscip Rev Syst Biol Med 1(2):159–171

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Evans DJW, Lawford PV, Gunn J, Walker E, Hose DR, Smallwood RH, Chopard B, Krafczyk M, Bernsdorf J, Hoekstra A (2008) The application of multiscale modelling to the process of development and prevention of stenosis in a stented coronary artery. Philos Trans A Math Phys Eng Sci 366:3343–3360

    Article  CAS  PubMed  Google Scholar 

  25. Groen D, Borgdorff J, Bona-Casas C, Hetherington J, Nash RW, Zasada SJ, Saverchenko I, Mamonski M, Kurowski K, Bernabeu MO, Hoekstra AG, Coveney PV (2013) Flexible composition and execution of high performance, high fidelity multiscale biomedical simulations. Interface Focus 3(2):2013

    Article  Google Scholar 

  26. Tahir H, Hoekstra AG, Lorenz E, Lawford PV, Hose DR, Gunn J, Evans DJW (2011) Multi-scale simulations of the dynamics of in-stent restenosis: impact of stent deployment and design. Interface Focus 1(3):365–373

    Article  PubMed Central  PubMed  Google Scholar 

  27. Tahir H, Bona-Casas C, Hoekstra AG (2013) Modelling the effect of a functional endothelium on the development of in-stent restenosis. PLoS One 8(6):e66138

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Amatruda CM, Casas CB, Keller BK, Tahir H, Dubini G, Hoekstra AG, Hose DR, Lawford P, Migliavacca F, Narracott AJ, Gunn J (2014) From histology and imaging data to models for in-stent restenosis. Int J Artif Organs 37(10):786–800

    Article  PubMed  Google Scholar 

  29. Tahir H, Bona-Casas C, Narracott AJ, Iqbal J, Gunn J, Lawford P, Hoekstra AG (2014) Endothelial repair process and its relevance to longitudinal neointimal tissue patterns: comparing histology with in silico modelling. J R Soc Interface 11(94):20140022

    Article  PubMed Central  PubMed  Google Scholar 

  30. Groen D, Zasada SJ, Coveney PV (2014) Survey of multiscale and multiphysics applications and communities. Comput Sci Eng 16(2):34–43

    Article  Google Scholar 

  31. Schnell S, Grima R, Maini PK (2007) Multiscale modeling in biology: new insights into cancer illustrate how mathematical tools are enhancing the understanding of life from the smallest scale to the grandest. Am Sci 95:134–142

    Article  Google Scholar 

  32. Hoekstra AG, Chopard B, Coveney P (2014) Multiscale modelling and simulation: a position paper. Phil Trans R Soc A 372(2021):20130377

    Article  PubMed  Google Scholar 

  33. Yang A, Marquardt W (2009) An ontological conceptualization of multiscale models. Comput Chem Eng 2009(33):822–837

    Article  Google Scholar 

  34. Damle S, Davidson E (2012) Synthetic in vivo validation of gene network circuitry. Proc Natl Acad Sci 109(5):1548–1553

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Borgdorff J, Belgacem MB, Bona-Casas C, Fazendeiro L, Groen D, Hoenen O, Mizeranschi A, Suter JL, Coster D, Coveney PV, Dubitzky W, Hoekstra AG, Strand P, Chopard B (2014) Performance of distributed multiscale simulations. Phil Trans A 372(2021):20130407

    Article  Google Scholar 

  36. Ciepiela E, Wilk B, Harężlak D, Kasztelnik M, Pawlik M, Bubak M (2014) Towards provisioning of reproducible, reviewable and reusable in-silico experiments with the GridSpace2 Platform. In: Bubak M, Kitowski J, Wiatr K (eds) eScience on distributed computing infrastructure, LNCS, vol 8500. Springer, Switzerland. p 118–129. http://link.springer.com/chapter/10.1007%2F978-3-319-10894-0_9

    Google Scholar 

  37. Piacentini A, Morel T, Thevenin A, Duchaine F (2011) Open-PALM: an open source dynamic parallel coupler. Proceedings of the 4th International conference on computational methods for coupled problems in science and engineering, Kos, Greece, p 20–22

    Google Scholar 

  38. Mitha F, Lucas TA, Feng F, Kepler TB, Chan C (2008) The Multiscale Systems Immunology project: software for cell-based immunological simulation. Source Code Biol Med 3:6

    Article  PubMed Central  PubMed  Google Scholar 

  39. Collier N, North M (2012) Repast HPC: a platform for large-scale agent-based modeling. In: Dubitzky W, Kurowski K, Schott B (eds) Large-scale computing techniques for complex system simulations. John Wiley, and Sons, Inc., Hoboken, NJ, pp 81–110

    Chapter  Google Scholar 

  40. Falcone J-L, Chopard B, Hoekstra A (2012) MML: towards a Multiscale Modeling Language. Procedia Comput Sci 1(2012):819–826

    Google Scholar 

  41. Carson JS (2002) Model verification and validation. In: Yücesan E, Chen CH, Snowdon J, Charnes J (eds) The 2002 winter simulation conference, p 52–58

    Google Scholar 

  42. Davison AP (2010) Challenges and solutions in replicability and provenance tracking for simulation projects. BMC Neurosci 11(Supp. 1):P76

    Article  PubMed Central  Google Scholar 

  43. Mark V (2013) Biology: the big challenges of big data. Nature 498:255–260

    Article  Google Scholar 

  44. Krauter K, Buyya R, Maheswaran M (2002) A taxonomy and survey of grid resource management systems for distributed computing. Softw Pract Exp 32:135–164

    Article  Google Scholar 

  45. Castillo C, Rouskas G, Harfoush K (2011) Online algorithms for advance resource reservations. J Parallel Distrib Comput 71(7):963–973

    Article  Google Scholar 

  46. Barabási A-L, Gulbahce N, Loscalzo J (2011) Network medicine: a network-based approach to human disease. Nat Rev Genet 12:56–68

    Article  PubMed Central  PubMed  Google Scholar 

  47. Martone ME, Zaslavsky I, Gupta A, Memon A, Tran J, Wong W, Fong L, Larson SD, Ellisman MH (2008) The Smart Atlas: spatial and semantic strategies for multiscale integration of brain data. In: Burger A, Davidson D, Baldock R (eds) Anatomy ontologies for bioinformatics, p 267–286

    Google Scholar 

  48. Fish J (2009) Multiscale methods: bridging the scales in science and engineering. Oxford University Press, Oxford

    Book  Google Scholar 

  49. Hoekstra AG, Copard B, Lawford P (2013) Multiscale modelling. In: Coveney P, Díaz-Zuccarini V, Hunter P, Viceconti M (eds) Computational biomedicine. Oxford University Press, Oxford, pp 138–159

    Google Scholar 

  50. Viceconti M (2012) Multiscale modeling of the skeletal system. Cambridge University Press, New York

    Google Scholar 

  51. Hunter P, Chapman T, Coveney PV, de Bono B, Diaz V, Fenner J, Frangi AF, Harris P, Hose R, Kohl P, Lawford P, McCormack K, Mendes M, Omholt S, Quarteroni A, Shublaq N, Skår J, Stroetmann K, Tegner J, Thomas SR, Tollis I, Tsamardinos I, van Beek JHGM, Viceconti M (2013) A vision and strategy for the virtual physiological human: 2012 update. Interface Focus 3:20130004

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgements

A.G. Hoekstra acknowledges partial funding by Russian Scientific Foundation, grant # 14-11-00826.

Author information

Authors and Affiliations

  1. Biomedical Sciences Research Institute, University of Ulster, Cromore Road, Coleraine, Co. Londonderry, BT52 1SA, UK

    Alexandru Mizeranschi & Werner Dubitzky

  2. Chemistry Department, Centre for Computational Science, University College London, 20 Gordon Street, WC1H 0AJ, London, UK

    Derek Groen

  3. Netherlands eScience Center, Science Park 140, 1098 XG, Amsterdam, The Netherlands

    Joris Borgdorff

  4. Computational Science Lab, Institute for Informatics, Faculty of Science, University of Amsterdam, Sciencepark 904, 1098 XH, Amsterdam, The Netherlands

    Alfons G. Hoekstra

  5. Advanced Computing Lab, ITMO University, 197101, 49 Kronverkskiy av., St. Petersburg, Russia

    Alfons G. Hoekstra

  6. Computer Science Department, University of Geneva, 7 route de Drize, 1227, Carouge, Switzerland

    Bastien Chopard

  7. School of Biomedical Sciences, University of Ulster, Coleraine campus, Cromore Road, Coleraine, Co. Londonderry, BT52 1SA, UK

    Werner Dubitzky

Authors
  1. Alexandru Mizeranschi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Derek Groen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joris Borgdorff
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alfons G. Hoekstra
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bastien Chopard
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Werner Dubitzky
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Werner Dubitzky .

Editor information

Editors and Affiliations

  1. Dept of Systems Biology & Bioinformatics, University of Rostock, Rostock, Germany

    Ulf Schmitz

  2. Dept of Systems Biology & Bioinformatics, University of Rostock, Rostock, Germany

    Olaf Wolkenhauer

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media New York

About this protocol

Cite this protocol

Mizeranschi, A., Groen, D., Borgdorff, J., Hoekstra, A.G., Chopard, B., Dubitzky, W. (2016). Anatomy and Physiology of Multiscale Modeling and Simulation in Systems Medicine. In: Schmitz, U., Wolkenhauer, O. (eds) Systems Medicine. Methods in Molecular Biology, vol 1386. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3283-2_17

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-3283-2_17

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3282-5

  • Online ISBN: 978-1-4939-3283-2

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation