Section: Application Domains

Models of mechanistic interactions between proteins

Computer Science takes a more and more important role in the design and the understanding of biological systems such as signaling pathways, self assembly systems, DNA repair mechanisms. Biology has gathered large data-bases of facts about mechanistic interactions between proteins, but struggles to draw an overall picture of how these systems work as a whole. High level languages designed in Computer Science allow one to collect these interactions in integrative models, and provide formal definitions (i.e., semantics) for the behavior of these models. This way, modelers can encode their knowledge, following a bottom-up discipline, without simplifying a priori the models at the risk of damaging the key properties of the system. Yet, the systems that are obtained this way suffer from combinatorial explosion (in particular, in the number of different kinds of molecular components, which can arise at run-time), which prevents from a naive computation of their behavior.

We develop various analyses based on abstract interpretation, and tailored to different phases of the modeling process. We propose automatic static analyses in order to detect inconsistencies in the early phases of the modeling process. These analyses are similar to the analysis of classical safety properties of programs. They involve both forward and backward reachability analyses as well as causality analyses, and can be tuned at different levels of abstraction. We also develop automatic static analyses in order to identify key elements in the dynamics of these models. The results of these analyses are sent to another tool, which is used to automatically simplify models. The correctness of this simplification process is proved by the means of abstract interpretation: this ensures formally that the simplification preserves the quantitative properties that have been specified beforehand by the modeler. The whole pipeline is parameterized by a large choice of abstract domains which exploits different features of the high level description of models.