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

Nicolas Levy (1, 2) , Aurélien Naldi (3) , Céline Hernandez (3) , Gautier Stoll (4) , Denis Thieffry (3) , Andrei Zinovyev (5) , Laurence Calzone (5) , Loïc Paulevé (1, 6)

1 BioInfo - LRI - Bioinformatique (LRI)
2 ENS de Lyon - École normale supérieure de Lyon
3 IBENS - Institut de biologie de l'ENS Paris
4 CRC - Centre de Recherche des Cordeliers
5 Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe
6 Inria Saclay - Ile de France

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. We rely on the CoLoMoTo Interactive Notebook to provide a thoroughly documented and executable notebook of our computational analysis. 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. Beyond the specific application considered here, the resulting Jupyter notebook constitutes a tutorial for the use and combination of several logical modelling tools, which can be easily adapted to analyse other models. Furthermore, the notebook web interface and the companion Docker distribution of logical modelling tools greatly facilitate the production of accessible and reproducible model analysis workflows.

Mots clés: Boolean networks; stochastic simulations; model verification; software tools; reproducibility

Domaines: Bio-informatique [q-bio.QM]

Nicolas Levy, Aurélien Naldi, Céline Hernandez, Gautier Stoll, Denis Thieffry, et al.. Prediction of Mutations to Control Pathways Enabling Tumour Cell Invasion with the CoLoMoTo Interactive Notebook (Tutorial). Frontiers in Physiology, 2018, 9, pp.787. ⟨10.1101/319780⟩. ⟨hal-01809081⟩