Prediction of Mutations to Control Pathways Enabling Tumour Cell Invasion with the CoLoMoTo Interactive Notebook (Tutorial)

Abstract

Boolean and multi-valued logical formalisms are increasingly used to model complex cellular networks. To ease the development and analysis of logical models, a series of software tools have been proposed, often with specific assets. However, combining these tools typically implies a series of cumbersome software installation and model conversion steps. In this respect, the CoLoMoTo Interactive Notebook provides a joint distribution of several logical modelling software tools, along with an interactive web Python interface easing the chaining of complementary analyses. In this protocol, we demonstrate the assets of this approach through the analysis of a computational model of biological network. Our computational workflow combines (1) the importation of a GINsim model and its display, (2) its format conversion using the Java library BioLQM, (3) the formal prediction of mutations using the OCaml software Pint, (4) the model checking using the C++ software NuSMV, (5) quantitative stochastic simulations using the C++ software MaBoSS, and (6) the visualisation of results using the Python library matplotlib. Starting with a recent Boolean model of the signalling network controlling tumour cell invasion and migration, our model analysis culminates with the prediction of sets of mutations presumably involved in a metastatic phenotype.