Geant4-DNA simulations using complex DNA geometries generated by the DnaFabric tool

Meylan, Sylvain; Vimont, Ulysse; Incerti, S.; Clairand, I.; Villagrasa, C.

doi:10.1016/j.cpc.2016.02.019

Cited by 45 publications

(62 citation statements)

References 24 publications

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“…Geant4‐DNA can already be used to study the production and transportation of chemical species, although only in liquid water . It will be interesting to perform simulations of the physico‐chemical and chemical stages of radiation in detailed DNA geometries when the processes will be available for the public in Geant4 . Finally, systematic in vitro and in vivo experimental measurements would be required to validate the therapeutic benefit of these promising MBRT modalities.…”

Section: Discussionmentioning

confidence: 99%

Minibeam radiation therapy: A micro‐ and nano‐dosimetry Monte Carlo study

et al. 2020

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Purpose Minibeam radiation therapy (MBRT) is an innovative strategy based on a distinct dose delivery method that is administered using a series of narrow (submillimetric) parallel beams. To shed light on the biological effects of MBRT irradiation, we explored the micro‐ and nanodosimetric characteristics of three promising MBRT modalities (photon, electron, and proton) using Monte Carlo (MC) calculations. Methods Irradiation with proton (100 MeV), electron (300 MeV), and photon (effective energy of 69 keV) minibeams were simulated using Geant4 MC code and the Geant4‐DNA extension, which allows the simulation of energy transfer points with nanometric accuracy. As the target of the simulations, cells containing spherical nuclei with or without a detailed description of the DNA (deoxyribonucleic acid) geometry were placed at different depths in peak and valley regions in a water phantom. The energy deposition and number of events in the cell nuclei were recorded in the microdosimetry study, and the number of DNA breaks and their complexity were determined in the nanodosimetric study, where a multi‐scale simulation approach was used for the latter. For DNA damage assessment, an adapted DBSCAN clustering algorithm was used. To compare the photon MBRT (xMBRT), electron MBRT (eMBRT), and proton MBRT (pMBRT) approaches, we considered the treatment of a brain tumor located at a depth of 75 mm. Results Both mean energy deposition at micrometric scale and DNA damage in the “valley” cell nuclei were very low as compared with these parameters in the peak region at all depths for xMBRT and at depths of 0 to 30 mm and 0 to 50 mm for eMBRT and pMBRT, respectively. Only the charged minibeams were favorable for tumor control by producing similar effects in peak and valley cells after 70 mm. At the micrometer scale, the energy deposited per event pointed to a potential advantage of proton beams for tumor control, as more aggressive events could be expected at the end of their tracks. At the nanometer scale, all three MBRT modalities produced direct clustered DNA breaks, although the majority of damage (>93%) was composed of isolated single strand breaks. The pMBRT led to a significant increase in the proportion of clustered single strand breaks and double‐strand breaks at the end of its range as compared to the entrance (7% at 75 mm vs 3% at 10 mm) in contrast to eMBRT and xMBRT. In the latter cases, the proportions of complex breaks remained constant, irrespective of the depth and region (peak or valley). Conclusions Enhanced normal tissue sparing can be expected with these three MBRT techniques. Among the three modalities, pMBRT offers an additional gain for radioresistant tumors, as it resulted in a higher number of complex DNA damage clusters in the tumor region. These results can aid understanding of the biological mechanisms of MBRT.

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Section: Discussionmentioning

confidence: 99%

Minibeam radiation therapy: A micro‐ and nano‐dosimetry Monte Carlo study

et al. 2020

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“…In our previous work, new software called DnaFabric was used to build the geometrical structure of the DNA contained in a fibroblast nucleus. DnaFabric is a stand‐alone software which enables three‐dimensional (3D) geometries to be generated, in particular, DNA structures from the molecular level to the whole genome representation.…”

Section: Methodsmentioning

confidence: 99%

Influence of chromatin compaction on simulated early radiation‐induced DNA damage using Geant4‐DNA

Tang

Bueno

Meylan³

et al. 2019

Medical Physics

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Purpose In this work, we present simulated double‐strand breaks (DSBs) obtained for two human cell nucleus geometries. The first cell nucleus represents fibroblasts, filled with DNA molecules in different compaction forms: heterochromatin or euchromatin only. The second one represents an endothelial cell nucleus, either filled with heterochromatin only or with a uniform distribution of 48% of heterochromatin and 52% of euchromatin, obtained from measurements carried out at IRSN. Protons and alpha particles of different energies were used as projectiles. Each cell nucleus model includes a multi‐scale description of the DNA target from the molecular level to the whole human genome representation. Methods The cell nucleus models were generated using an extended version of the DnaFabric software in which a new model of euchromatin was implemented in addition to the existing model of heterochromatin. Thus, each nucleus model contains the complete human genome (a total of 6 Gbp) in the G0/G1 phase of the cycle, filled with a continuous chromatin fiber per chromosome that can take into account the heterochromatin and the euchromatin compaction. These geometries were then exported to a simulation chain using the Monte Carlo toolkit Geant4‐DNA to perform computations of the physical, physicochemical, and chemical stages, in order to evaluate the influence of chromatin compaction on DSB induction and the contribution of direct and indirect damage, as well as DSB complexity. Results More direct damage and less indirect damage were observed in the heterochromatin than in the euchromatin. Nevertheless, no difference in terms of DSB complexity was observed between those formed in the heterochromatin or the euchromatin models. Yields of DSB/Gy/Gbp show an increase when both heterochromatin and euchromatin models are taken into account, compared to when only heterochromatin is considered. Conclusions The results presented indicate that the chromatin compaction decreases DNA damage generated by ionizing radiation and thus, DNA compaction should be considered for the simulation of DNA repair and other cellular outcomes.

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“…Users can however also model single chromatin fibers or single double helix strands. TOPAS-nBio can read in geometries from the Protein Data Bank (PDB) [13] as well as DNAFabric [14] (see Figure 1c). Although nuclear DNA is a primary radiation target, TOPAS-nBio allows other non-nuclear target sites to be modeled (e.g., mitochondria [15, 16]).…”

Section: Methodsmentioning

confidence: 99%

Validation of the radiobiology toolkit TOPAS-nBio in simple DNA geometries

et al. 2017

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Computational simulations offer a powerful tool for quantitatively investigating radiation interactions with biological tissue and can help bridge the gap between physics, chemistry and biology. The TOPAS collaboration is tackling this challenge by extending the current Monte Carlo tool to allow for sub-cellular in silico simulations in a new extension, TOPAS-nBio. TOPAS wraps and extends the Geant4 Monte Carlo simulation toolkit and the new extension allows the modeling of particles down to vibrational energies (~ 2 eV) within realistic biological geometries. Here we present a validation of biological geometries available in TOPAS-nBio, by comparing our results to two previously published studies. We compare the prediction of strand breaks in a simple linear DNA strand from TOPAS-nBio to a published Monte Carlo track structure simulation study. While TOPAS-nBio confirms the trend in strand break generation, it predicts a higher frequency of events below an energy of 17.5 eV compared to the alternative Monte Carlo track structure study. This is due to differences in the physics models used by each code. We also compare the experimental measurement of strand breaks from incident protons in DNA plasmids to TOPAS-nBio simulations. Our results show good agreement of single and double strand breaks predicting a similar increase in the strand break yield with increasing LET.

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Geant4-DNA simulations using complex DNA geometries generated by the DnaFabric tool

Cited by 45 publications

References 24 publications

Minibeam radiation therapy: A micro‐ and nano‐dosimetry Monte Carlo study

Minibeam radiation therapy: A micro‐ and nano‐dosimetry Monte Carlo study

Influence of chromatin compaction on simulated early radiation‐induced DNA damage using Geant4‐DNA

Validation of the radiobiology toolkit TOPAS-nBio in simple DNA geometries

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