Biomedical Engineering Reference
In-Depth Information
the repair of DNA. Having a complete model would open very interesting
avenues for health care. For instance, it would allow personalized treatment
planning taking into account the patient's genomic data. But it involves diffi -
cult challenges:
• Interaction of ionizing particles with DNA takes place through direct and
indirect processes which are too complex to describe and simulate.
• An accurate multiscale model of the living organism is needed. The mul-
tiscale approach is needed because damage to DNA takes place at a
molecular level on an extremely short time scale while DNA repair is a
global response of the organism.
• DNA repair mechanisms are still poorly understood.
Finally, accurate modeling is very computationally intensive because mul-
tiscale approaches involve handling large and complex images describing the
geometry of the medium in which the interaction of ionizing particles has to
be tracked down to very low energies to correctly describe indirect damage
to DNA.
Since 2002, our research groups have been building the software pieces
relevant to this global task of modeling living organisms under radiation expo-
sure. Our modeling efforts have been mostly deployed on grid infrastructures
and driven by experimental evidence. The choice of deploying our computa-
tions on grids was driven by opportunity.
It is well known that building a model involving all the biological levels
cannot be achieved, but the current challenge is to provide a fully integrative
framework on the various levels of a whole organism to understand the con-
nections between them. So, as a fi rst step, we have decided to split a radiobiol-
ogy study in three parts: the irradiation of the real organism, the simulation
of the radiation process and its impact on biological structures, and fi nally the
simulation of organism development after radiation exposure.
The Geant4/GATE [37, 38] toolkit will be used to simulate physical interac-
tions between particles and organisms down to the cellular and DNA levels.
The specifi c goal of the Geant4-DNA project started in 2010 is to provide
probabilistic damage onto the DNA structure after radiation exposure of
several particle types [39] .
Simulating the development of an organism is a great challenge. One mod-
eling approach is to use the most common models for the various biological
processes. However, this will lead to a set of unlinked models. The complexity
can be tackled by several means: using a few common modeling concepts that
are valid through scales, using a biologylike process such as morphogenesis
principles to simulate growth and evolving, and using coupling schemes to
make the various models work together [40, 41].
Our approach is to use cellular automata [42] as a common framework, but
by relaxing it from the classic defi nition to a more suitable one for biological
applications and by proposing a multiscale model. In order to follow as much
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