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MPI
for Molecular Genetics -
Computational
Molecular Biology
Model Expansion Experimental Design
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A set of scripts for logical modeling, the MEEDalg program, and the exp package provide tools for different components of a common systems biology framework [Szczurek et al.]. The framework proceeds in three steps:
- Building a logical model of the signaling pathway under study, and using it to provide predictions for a set of candidate experiments
- Selecting perturbation experiments on the pathway
- Learning transcriptional regulation downstream of the pathway
A User Guide to application of the framework using our tools provides an example of the yeast signaling model and perturbation microarray data.
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Download
Download the whole set of tools with documentation. It contains software facilitating ALL the particular components of the framework that are described and available for separate downloads below (so all the downloadable links on this site are gathered here).
Logical modeling
The available prior knowledge about the signaling network under study needs to be formalized in a form of a logical model. Logical modeling step involves building the model and using it to provide predictions about the response of possible targets in a set of candidate experiments.
The logical model can be built and saved in a set of files using a MetaReg GUI interface (go to http://acgt.cs.tau.ac.il/metareg/ for download of the MetaReg software, its documentation and references about the theory of logical modeling. There is an application note and links to publications on this website). A set of command-line scripts needs to be run including a prediction engine to get a final set of input files for MEEDalg.
MEED algorithm
We provide a C++ source code for the MEEDalg tool. MEEDalg takes as input the set of files generated in the previous step (using the MetaReg application and command-line scripts) and provides on output selected perturbation experiments and model predictions for those experiments, which are utilized by the expansion procedure (exp package) for learning gene regulation.
Model expansion
  exp is an R package for model expansion. It allows to identify target genes, their regulators in a given pathway and the mechanism of regulation (activation/repression).
It takes as input (i) predictions from the pathway model, and (ii) gene expression data in the same set of pathway perturbations (designed by MEEDalg). The output are regulatory modules of the genes assigned to different regulatory programs.
References
- Ewa Szczurek, Irit Gat-Viks, Jerzy Tiuryn and Martin Vingron. Elucidating Regulatory Mechanisms Downstream of a Signaling Pathway Using Informative Experiments. Molecular Systems Biology 5, 257, Epub 2009 Jul 7.
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