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Jeudi 3 Février, Elisabetta De Maria, INRIA Rocquencourt |
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Written by Pierre PETERLONGO
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Computer Science Logic for Structure Prediction, String
Comparison, and Model Coupling.
10h30 Salle Aurigny
Formal methods of Computer Science are more and more applied
to the study of biological issues. In literature, they are extensively
used to model and simulate biological systems and to express formal
properties of such systems. In the talk I'll show how model checking,
game theory, and the combination of temporal logic and parameter
learning techniques can be exploited to develop effective solutions to
three relevant classes of biological problems: the protein structure
prediction and protein folding problems, the sequence comparison
problems, and the problems of coupling biological models and validating
the resulting model.
As for the protein structure prediction and protein folding problems, we
model the space of protein conformations as a finite transition system
whose states are all the possible conformations of a protein and whose
transitions represent admissible transformations of conformations. Then,
we show how meaningful properties of such a transition system can be
expressed in temporal logic and we use the model checking machinery to
algorithmically check them.
As for the sequence comparison problems, we model biological sequences
as labeled structures with a "limited order" relation and we define a
criterion which allows one to measure their degree of similarity in
terms of the number of remaining rounds in an Ehrenfeucht-Fraissé game
played on such structures.
Finally, as for the last issue is concerned, we study the coupling of
different models playing a role in the mammalian cell cycle and in
cancer therapies. We show how the formalization of experimental
observations in temporal logic with numerical constraints can be used to
automatically validate a coupled model and optimize unknown parameter
values with respect to experimental data. We illustrate this
constraint-based approach through the coupling of existing biochemical
models of the mammalian cell cycle, the circadian clock, the p53/Mdm2
DNA-damage repair system, and irinotecan metabolism.
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