Skip to main content
SpringerLink
Log in
Book cover

Italian Workshop on Artificial Life and Evolutionary Computation

WIVACE 2018: Artificial Life and Evolutionary Computation pp 127–137Cite as

Dynamic DNA Damage and Repair Modeling: Bridging the Gap Between Experimental Damage Readout and Model Structure

  • Conference paper
  • First Online:

Part of the book series: Communications in Computer and Information Science ((CCIS,volume 900))

Abstract

In this work, a method is presented to map a set of experimentally obtained, time-resolved distributions to a dynamic model. Specifically, time-resolved comet assay readouts of cancer cells after application of ionizing radiation are mapped to the Multi-Hit-Repair model, a radiobiologically motivated dynamic model used to predict DNA damage and repair. Differential evolution is used for parameter-search to showcase the potential of this method, producing a prediction close to the experimental measurement. The results obtained from the parameter search are used to characterize aspects of the repair process. The method is compared to prior attempts of finding model parameters from dose-response curves, revealing that calibration is required to render the two comparable.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   49.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   64.99
Price excludes VAT (USA)
  • Compact, lightweight 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

Learn about institutional subscriptions

References

  1. Albert, C., Künsch, H.R., Scheidegger, A.: A simulated annealing approach to approximate Bayes computations. Stat. Comput. 25(6), 1217–1232 (2015)

    Article  MathSciNet  Google Scholar 

  2. Barnard, S., Bouffler, S., Rothkamm, K.: The shape of the radiation dose response for DNA double-strand break induction and repair. Genome Integr. 4(1), 1 (2013)

    Article  Google Scholar 

  3. Besserer, J., Schneider, U.: A track-event theory of cell survival. Zeitschrift fuer Medizinische Physik 25(2), 168–175 (2015)

    Article  Google Scholar 

  4. Dale, R.G.: The application of the linear-quadratic dose-effect equation to fractionated and protracted radiotherapy. Br. J. Radiol. 58(690), 515–528 (1985)

    Article  Google Scholar 

  5. Guerrero, M., Li, X.A.: Extending the linear-quadratic model for large fraction doses pertinent to stereotactic radiotherapy. Phys. Med. Biol. 49(20), 4825 (2004)

    Article  Google Scholar 

  6. Hartmann, A., et al.: Recommendations for conducting the in vivo alkaline comet assay. Mutagenesis 18(1), 45–51 (2003)

    Article  Google Scholar 

  7. Kinner, A., Wu, W., Staudt, C., Iliakis, G.: \(\gamma \)-h2ax in recognition and signaling of dna double-strand breaks in the context of chromatin. Nucleic acids research 36(17), 5678–5694 (2008)

    Article  Google Scholar 

  8. Kumaravel, T., Jha, A.N.: Reliable comet assay measurements for detecting dna damage induced by ionising radiation and chemicals. Mutat. Res./Genet. Toxicol. Environ. Mutagen. 605(1), 7–16 (2006)

    Article  Google Scholar 

  9. Kuo, L.J., Yang, L.X.: \(\gamma \)-h2ax-a novel biomarker for dna double-strand breaks. In vivo 22(3), 305–309 (2008)

    MathSciNet  Google Scholar 

  10. Lea, D.E.: Actions of Radiations on Living Cells. Cambridge University Press, Cambridge (1946)

    Google Scholar 

  11. Mariotti, L.G., et al.: Use of the \(\gamma \)-h2ax assay to investigate DNA repair dynamics following multiple radiation exposures. PloS ONE 8(11), e79541 (2013)

    Article  Google Scholar 

  12. Mori, R., Matsuya, Y., Yoshii, Y., Date, H.: Estimation of the radiation-induced DNA double-strand breaks number by considering cell cycle and absorbed dose per cell nucleus. J. Radiat. Res. 59(3), 253–260 (2018)

    Article  Google Scholar 

  13. Olive, P.L., Banáth, J.P.: The comet assay: a method to measure DNA damage in individual cells. Nat. Protoc. 1, 23–29 (2006)

    Article  Google Scholar 

  14. Scheidegger, S., Fuchs, H.U., Zaugg, K., Bodis, S., Füchslin, R.M.: Using state variables to model the response of tumour cells to radiation and heat: a novel multi-hit-repair approach. Comput. Math. Methods Med. 2013, 15 (2013). https://www.hindawi.com/journals/cmmm/2013/587543/

  15. Schulz, N., et al.: Dynamic in vivo profiling of DNA damage and repair after radiotherapy using canine patients as a model. Int. J. Mol. Sci. 18(6), 1176 (2017)

    Article  Google Scholar 

  16. Storn, R., Price, K.: Differential evolution–a simple and efficient heuristic for global optimization over continuous spaces. J. Glob. Optim. 11(4), 341–359 (1997)

    Article  MathSciNet  Google Scholar 

  17. Wang, Y., et al.: Evaluation of the comet assay for assessing the dose-response relationship of DNA damage induced by ionizing radiation. Int. J. Mol. Sci. 14(11), 22:449–22:461 (2013)

    Article  Google Scholar 

  18. Weyland, M., Thumser-Henner, P., Nytko, K., Rohrer Bley, C., Füchslin, R., Scheidegger, S.: Proceedings: extracting information about cellular repair processes after hyperthermia - radiotherapy by model-based data analysis - ambiguities in survival prediction as a challenge? Strahlenther Onkol 194(5), 503–504 (2018)

    Google Scholar 

  19. Zaider, M., Hanin, L.: Tumor control probability in radiation treatment. Med. Phys. 38(2), 574–583 (2011)

    Article  Google Scholar 

Download references

Funding

This work was supported by the Swiss National Foundation (grant number 320030_163435) – Stephan Scheidegger; Carla Rohrer Bley.

Author information

Authors and Affiliations

  1. Zurich University of Applied Sciences, Winterthur, Switzerland

    Mathias S. Weyland, Simone Ulzega, Stephan Scheidegger & Rudolf M. Füchslin

  2. Division of Radiation Oncology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland

    Pauline Thumser-Henner & Carla Rohrer Bley

  3. Center for Applied Biotechnology and Molecular Medicine (CABMM), University of Zurich, Zurich, Switzerland

    Pauline Thumser-Henner & Carla Rohrer Bley

  4. Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland

    Pauline Thumser-Henner

  5. BioNanomaterials Group, Adolphe Merkle Institute, University of Fribourg, Fribourg, Switzerland

    Mathias S. Weyland & Alke Petri-Fink

  6. Department of Chemistry, University of Fribourg, Fribourg, Switzerland

    Alke Petri-Fink & Marco Lattuada

Authors
  1. Mathias S. Weyland
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pauline Thumser-Henner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carla Rohrer Bley
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Simone Ulzega
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alke Petri-Fink
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marco Lattuada
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Stephan Scheidegger
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rudolf M. Füchslin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mathias S. Weyland .

Editor information

Editors and Affiliations

  1. University of Parma, Parma, Italy

    Stefano Cagnoni

  2. University of Parma, Parma, Italy

    Monica Mordonini

  3. Università degli Studi eCampus, Novedrate, Italy

    Riccardo Pecori

  4. University of Bologna, Cesena, Italy

    Andrea Roli

  5. University of Modena and Reggio Emilia, Modena, Italy

    Marco Villani

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this paper

Check for updates. Verify currency and authenticity via CrossMark

Cite this paper

Weyland, M.S. et al. (2019). Dynamic DNA Damage and Repair Modeling: Bridging the Gap Between Experimental Damage Readout and Model Structure. In: Cagnoni, S., Mordonini, M., Pecori, R., Roli, A., Villani, M. (eds) Artificial Life and Evolutionary Computation. WIVACE 2018. Communications in Computer and Information Science, vol 900. Springer, Cham. https://doi.org/10.1007/978-3-030-21733-4_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-21733-4_10

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-21732-7

  • Online ISBN: 978-3-030-21733-4

  • eBook Packages: Computer ScienceComputer Science (R0)

Publish with us

Policies and ethics

Search

Navigation