April 26, 2017, Wednesday

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CABERNET

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".

Contents

CABERNET

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                  

  • Random networks with specified structural properties. Given the key parameters, CABERNET can generate and simulate ensembles of random networks with shared features.
  • Import of characterized GRNs. GRNs that are characterized with respect to both the topology and the regulatory functions, either fetched from public datasets via Cytoscape or loaded via input textual file, can be processed with CABeRNET.
  • Augmentation of partial networks. Given partially defined networks as input, e.g., from publicly available dataset or known GRNs, CABERNET can augment the networks according to key structural and topological parameters.

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.


Screenshot of CABERNET app   Screenshot of CABERNET app: ATM and TES views

Manual and Tutorial

The manual of the plugin can be downloaded at this link.
A complete tutorial can be found here.

Licence

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.

  1. Download the file at this link.
  2. Open the Apps —> App Manager dialog (of Cytoscape).
  3. Unzip CABERNET-1.1.jar.zip file and than import CABERNET-1.1.jar using the “Install from file” button in the “Install Apps” tab.
  4. You will find the item CABERNET in the Apps menu.
  5. Run the App.

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. 

Example differentiation tree. The descendent of a unique stem cell type are two distinct differentiated cell types. 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.

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.