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* Corresponding author 1 LBBE - Laboratoire de Biométrie et Biologie Evolutive 2 Novadiscovery Lyon

Abstract : Quantitative modeling in systems biology can be difficult due to the scarcity of quantitative details about biological phenomenons, especially at the subcellular scale. An alternative to escape this difficulty is qualitative modeling since it requires few to no quantitative information. Among the qualitative modeling approaches, the Boolean network formalism is one of the most popular. However, Boolean models allow variables to be valued at only true or false, which can appear too simplistic when modeling biological processes. Consequently, this work proposes a modeling approach derived from Boolean networks where fuzzy operators are used and where edges are tuned. Fuzzy operators allow variables to be continuous and then to be more finely valued than with discrete modeling approaches, such as Boolean networks, while remaining qualitative. Moreover, to consider that in a given biological network some interactions are slower and-or weaker relative to other ones, edge states are computed in order to modulate in speed and strength the signal they convey. The proposed formalism is illustrated through its implementation on a tiny sample of the epidermal growth factor receptor signaling pathway. The obtained simulations show that continuous results are produced, thus allowing finer analysis, and that modulating the signal conveyed by the edges allows their tuning according to knowledge about the modeled interactions, thus incorporating more knowledge. The proposed modeling approach is expected to bring enhancements in the ability of qualitative models to simulate the dynamics of biological networks while not requiring quantitative information.

Keywords : qualitative modeling logic-based modeling Boolean networks biological networks fuzzy logic edge tuning in silico

Author: Arnaud Poret - Claudio Monteiro Sousa - Jean-Pierre Boissel -

Source: https://hal.archives-ouvertes.fr/


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