A Cytoscape 3 app for augmented boolean models of gene regulatory networks
CABERNET - Cytoscape app for Augmented Boolean modEls of gene Regulatory NETwork - is an App for Cytoscape, based on a dynamical model of cell differentiation originally described in "Villani M, Barbieri A, Serra R (2011) A Dynamical Model of Genetic Networks for Cell Differentiation. PLoS ONE 6(3): e17703. doi:10.1371/journal.pone.0017703".
CABERNET is a Cytoscape 3.2.0 app for the generation, the simulation, the analysis and the visualization of Boolean models of gene regulatory networks, particularly focused on the investigation of their robustness. CABERNET introduces a series of innovative simulation and analysis features, which can be divided in six main stages:
1. Network generation
2. Network simulation. The attractor landscape and the properties of the steady states (i.e., attractors) of the networks can be extensively investigated.
3. Network selection. Given an input differentiation tree, the app allows to search for NRBNs whose emergent behaviour is in accordance with the input tree (in terms of the expected stability and dynamical trajectory). The app is based on a generative approach, i.e., NRBNs are randomly created according to user-defined features such as statistical properties and topologies, and a batch process accepts/discard the GRNs matching the input lineage commitment tree.
4. Robustness analysis. Different kind of perturbations can be performed on the networks and the relative stability can be subsequently assessed via robustness analyses, for instance by analyzing measures such as avalanches and sensitivity.
5. Network analyses. A wide range of statical and dynamical properties of the simulated network can be analyzed with CABERNET.
6. Visualization. The powerful visualization capabilities of Cytoscape can be used to analyze the topological and dynamical properties of the simulated networks.
Manual and Tutorial
The plugin is release under a BSD-like license which can be found in the COPYING file.
How to install
IMPORTANT NOTE: CABERNET is compatible with Cytoscape 3.2.0, it has not been tested with other versions of the application.
Example differentiation trees
At the following links you can find the txt file of two example differentiation trees, a trivial one and the real differentiation tree of intestinal crypts (see the relative figures below):
Note. We remark that given the high complexity of the differentiation tree of intestinal crypts the computation time can accordingly be very large.
Left figure: Example differentiation tree. The descendent of a unique stem cell type are two distinct differentiated cell types. Right figure: Schematic representation of the crypt differentiation tree. Stem cells are the root of the tree, while the 4 differentiated cell types (i.e. Paneth, Goblet, enteroendocrine, absorptive or enterocyte) are the leaves. TA stands for transit amplifying stage, which is known to be the intermediate state between stem and fully differentiated stages.
Credits and contacts
CABERNET was developed by Andrea Paroni, under the supervision of Alex Graudenzi, Giulio Caravagna, Giancarlo Mauri and Marco Antoniotti. For any question, comment, suggestion please write to: marco.antoniotti [a] disco.unimib.it.