Skip to main content

Validation of Modeling and Simulation Methods in Computational Biology

  • Conference paper
  • First Online:
GeNeDis 2018

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1194))

Abstract

In recent years, a highly sophisticated array of modeling and simulation tools in all areas of biological and biomedical research has been developed. These tools have the potential to provide new insights into biological mechanisms integrating subcellular, cellular, tissue, organ, and potentially whole organism levels. Current research is focused on how to use these methods for translational medical research, such as for disease diagnosis and understanding, as well as drug discovery. In addition, these approaches enhance the ability to use human-derived data and to contribute to the refinement of high-cost experimental-based research. Additionally, the conflicting conceptual frameworks and conceptions of modeling and simulation methods from the broad public of users could have a significant impact on the successful implementation of aforementioned applications. This in turn could result in successful collaborations across academic, clinical, and industrial sectors. To that end, this study provides an overview of the frameworks and disciplines used for validation of computational methodologies in biomedical sciences.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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

Similar content being viewed by others

References

  • Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002) The compartmentalization of cells. Garland Science; Ch 12

    Google Scholar 

  • Althoff M (2015) An introduction to cora 2015. In Proc. of the workshop on applied verification for continuous and hybrid systems, 34:120–151

    Google Scholar 

  • Althoff M, Stursberg O, Buss M (2008) Reachability analysis of nonlinear systems with uncertain parameters using conservative linearization. 47th IEEE conference on decision and control. IEEE, pp 4042–4048

    Google Scholar 

  • Bartocci E, Lio P (2016) Computational modeling, formal analysis, and tools for systems biology. PLoS Comput Biol 12(1):e1004591

    Article  Google Scholar 

  • Batt G, Ropers D, De Jong H, Geiselmann J, Mateescu R, Page M, Schneider D, et al (2005) Analysis and verification of qualitative models of genetic regulatory networks: a model-checking approach. IJCAI’05 Proceedings of the 19th international joint conference on Artificial intelligence, pp 370–375

    Google Scholar 

  • Batt G, Belta C, Weiss R (2007a) Model checking genetic regulatory networks with parameter uncertainty. HSCC 7:61–75. Springer

    Google Scholar 

  • Batt G, Belta C, Weiss R (2007b) Model checking liveness properties of genetic regulatory networks. Tools and algorithms for the construction and analysis of systems. pp 323–338

    Google Scholar 

  • Batt G, De Jong H, Page M, Geiselmann J (2008a) Symbolic reachability analysis of genetic regulatory networks using discrete abstractions. Automatica 44(4):982–989

    Article  Google Scholar 

  • Batt G, Belta C, Weiss R (2008b) Temporal logic analysis of gene networks under parameter uncertainty. IEEE Trans Automatic Control 53(Special Issue):215–229

    Article  Google Scholar 

  • Berman S, Halasz A, Kumar V (2007) Marco: areachability algorithm for multi-affine systems with applications to biological systems. In: International workshop on hybrid systems: computation and control. Springer, Berlin, Heidelberg, pp 76–89

    Google Scholar 

  • Bernot G, Comet JP, Snoussi EH (2014) Formal methods applied to gene network modelling, pp 245–289. https://doi.org/10.1002/9781119005223.ch7

  • Brim L, ÄŒeÅ¡ka M, Å afránek D (2013) Model checking of biological systems. In: Formal methods for dynamical systems. Springer, Berlin, Heidelberg, pp 63–112

    Google Scholar 

  • Burrage K, Hancock J, Leier A, Nicolau DV Jr (2007) Modelling and simulation techniques for membrane biology. Brief Bioinform 8:234–244

    Article  CAS  Google Scholar 

  • Calzone L, Fages F, Soliman S (2006) Biocham: an environment for modeling biological systems and formalizing experimental knowledge. Bioinformatics 22(14):1805–1807

    Article  CAS  Google Scholar 

  • Carson JS (2002) Verification validation: model verification and validation. In Proceedings of the 34th conference on Winter simulation: exploring new frontiers (WSC ‘02). Winter Simulation Conference, pp 52–58

    Google Scholar 

  • Chicone C (2016) An invitation to applied mathematics: differential equations. Modeling and Computation, Academic Press, San Diego

    Google Scholar 

  • Dang T, Le Guernic C, Maler O (2011) Computing reachable states for nonlinear biological models. Theor Comput Sci 412(21):2095–2107

    Article  Google Scholar 

  • Dreossi T (2017) Sapo: reachability computation and parameter synthesis of polynomial dynamical systems. In: Proceedings of the 20th international conference on hybrid systems: computation and control. (HSCC ‘17). ACM, New York, NY, USA, pp 29–34

    Google Scholar 

  • Drulhe S, Ferrari-Trecate G, De Jong H (2008) The switching threshold reconstruction problem for piecewise-affine models of genetic regulatory networks. IEEE Trans Automatic Control 53(Special Issue):153–165

    Article  Google Scholar 

  • Fages F, Soliman S (2008) Abstract interpretation and types for systems biology. Theor Comput Sci 403(1):52–70

    Article  Google Scholar 

  • Fang FC, Casadevall A (2011) Reductionistic and holistic science. Infect Immun 79:1401–1404

    Article  CAS  Google Scholar 

  • FDA (2011) Advancing regulatory science at FDA: a strategic plan. U.S. Food and Drug Administration, Silver Spring

    Google Scholar 

  • Frehse G, Le Guernic C, Donze A, Cotton S, Ray R, Lebeltel O, Ripado R, Girard A, Dang T, Maler O (2011) Spaceex: scalable verification of hybrid systems. In: Computer aided verification. Springer, Berlin, Heidelberg, pp 379–395

    Google Scholar 

  • Haddad T, Himes A, Thompson L, Irony T, Nair R, MDIC Computer Modeling and Simulation Working Group Participants (2017) Incorporation of stochastic engineering models as prior information in Bayesian Medical Device Trials. J Biopharm Stat 27(6):1089–1103

    Google Scholar 

  • Janes KA, Lauffenburger DA (2006) A biological approach to computational models of proteomic networks. Curr Opin Chem Biol 10(1):73–80

    Article  CAS  Google Scholar 

  • Kitano H (2002) Computational systems biology. Nature 420(6912):206–210

    Article  CAS  Google Scholar 

  • Le Novere N (2015) Quantitative and logic modelling of molecular and gene networks. Nat Rev Genet 16:146–158

    Article  Google Scholar 

  • Macklin DN, Ruggero NA, Covert MW (2014) The future of whole-cell modeling. Curr Opin Biotechnol 28:111–115

    Article  CAS  Google Scholar 

  • Miguel CM, Góngora PA, Rosenblueth DA (2012) An overview of existing modeling tools making use of model checking in the analysis of biochemical networks. Front Plant Sci 3:2012

    Google Scholar 

  • Moraru II, Schaff JC, Slepchenko BM, Blinov M et al (2008) The virtual cell modeling and simulation software environment. IET Syst Biol 2:352–362

    Article  CAS  Google Scholar 

  • Novikoff AB (1945) The concept of integrative levels and biology. Science 101:209–215

    Article  CAS  Google Scholar 

  • Oulas A, et al (2017) Systems bioinformatics: increasing precision of computational diagnostics and therapeutics through network-based approaches. Brief Bioinform 20(3):806–824

    Google Scholar 

  • Oyama S (2000) The ontogeny of information: developmental systems and evolution. Duke University Press, 296 p, ISBN-13: 978-0822324669

    Google Scholar 

  • Pardini G (2011) Formal modelling and simulation of biological systems with spatiality. PhD thesis. Universita di Pisa

    Google Scholar 

  • Patterson EA, Whelan MP (2017) A framework to establish credibility of computational models in biology. Prog Biophys Mol Biol 129:13–19

    Article  Google Scholar 

  • Pearson O (2014) Epigenetics: linking genotype and phenotype in development and evolution. In: Hallgrímsson B, Hall BK (eds) University of California Press, Berkeley, 472 pp., ISBN: 978-0-520-26709-1. HOMO – Journal of Comparative Human Biology. https://doi.org/10.1016/j.jchb.2013.11.002.

  • Piazza C, Antoniotti M, Mysore V, Policriti A, Winkler F, Mishra B (2005) Algorithmic algebraic model checking I: challenges from systems biology. In: Etessami K, Rajamani SK (eds) Computer aided verification. CAV 2005. Lecture Notes in Computer Science, vol 3576. Springer, Berlin, Heidelberg

    Google Scholar 

  • Platzer A (2007) Differential dynamic logic for verifying parametric hybrid systems. In: Tableaux, vol 4548. Springer, Berlin, Heidelberg, pp 216–232

    Google Scholar 

  • Platzer A (2008) Differential dynamic logic for hybrid systems. J Autom Reason 41(2):143–189

    Article  Google Scholar 

  • Platzer A, Quesel JD (2008) Keymaera: a hybrid theorem prover for hybrid systems (system description). In: International joint conference on automated reasoning. Springer, Berlin, Heidelberg, pp 171–178

    Google Scholar 

  • Rahmandad H, Sterman JD (2012) Reporting guidelines for simulation-based research in social sciences. Syst Dyn Rev 28(4):396–411

    Article  Google Scholar 

  • Ramdani N, Meslem N, Candau Y (2008) Reachability of uncertain nonlinear systems using a nonlinear hybridization. Lecture Notes Comput Sci 4981:415–428

    Article  Google Scholar 

  • Regev A, Panina EM, Silverman W, Cardelli L, Shapiro E (2004) Bioambients: an abstraction for biological compartments. Theor Comput Sci 325(1):141–167

    Article  Google Scholar 

  • Samaga R, Klamt S (2013) Modeling approaches for qualitative and semi-quantitative analysis of cellular signaling networks. Cell Commun Signal 11(1):43

    Article  Google Scholar 

  • Slepchenko BM, Schaff JC, Carson JH, Loew LM (2002) Computational cell biology: spatiotemporal simulation of cellular events. Annu Rev Biophys Biomol Struct 31:423–441

    Article  CAS  Google Scholar 

  • Snyder A (1986) Encapsulation and inheritance in object-oriented programming languages. ACM SIGPLAN Not 21. ACM:38–45

    Article  Google Scholar 

  • Testylier R, Dang T (2012) Analysis of parametric biological models with non-linear dynamics. arXiv preprint arXiv:1208.3849

    Google Scholar 

  • Vanlier J, Tiemann CA, Hilbers PAJ, Van Riel NAW (2013) Parameter uncertainty in biochemical models described by ordinary differential equations. Math Biosci 246(2):305–314

    Article  CAS  Google Scholar 

  • Viceconti M, Henney A, Morley-Fletcher E (2016) In silico clinical trials: how computer simulation will transform the biomedical industry. Int J Clin Trials 3(2):37–46

    Article  Google Scholar 

  • Wilkinson DJ (2011) Stochastic modelling for systems biology. Chapman & Hall, CRC Press, 384 p, ISBN 9781138549289

    Google Scholar 

  • Winslow RL, Trayanova N, Geman D, Miller MI (2012) Computational medicine: translating models to clinical care. Sci Transl Med 4(158):158rv111

    Article  Google Scholar 

  • Yang XS (2017) Engineering mathematics with examples and applications. Academic Press, San Diego

    Google Scholar 

Download references

Acknowledgdment

Τhe research work was supported by the Hellenic Foundation for Research and Innovation (HFRI) and the General Secretariat for Research and Technology (GSRT), under the HFRI PhD Fellowship grant (GA. no. 2096).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Antigoni Avramouli .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this paper

Check for updates. Verify currency and authenticity via CrossMark

Cite this paper

Avramouli, A. (2020). Validation of Modeling and Simulation Methods in Computational Biology. In: Vlamos, P. (eds) GeNeDis 2018. Advances in Experimental Medicine and Biology, vol 1194. Springer, Cham. https://doi.org/10.1007/978-3-030-32622-7_30

Download citation

Publish with us

Policies and ethics