Logical Modelling, Some Recent Methodological Advances Illustrated

Logical modelling is a popular mathematical framework for assessing the behaviour of regulatory and signalling networks. Despite its qualitative nature, it allows disclosing crucial dynamical properties. Here we briefly present the modelling formalism and recent challenges arising when building models and analysing them. We then introduce a few methodological advances for model synthesis and analysis, and illustrate their effectiveness with two applications. The first deals with a Boolean model explaining the early differentiation of Hematopoietic Stem Cells and biases that appear during ageing. This case study demonstrates a successful procedure for model synthesis from biological data as well as a method for model revision. The second application concerns the role of the micro-environment in the Epithelial to Mesenchymal Transition, a process by which epithelial cells lose their adhesive properties to gain migration ability. This case study illustrates the capacity of developed methods to handle networks with a few dozens components and to conclude on relevant dynamical properties. The paper ends with a discussion, pointing to open challenges that need to be tackled to further increase logical modelling applicability to disease networks.