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"Antelope": a hybrid-logic model checker for branching-time Boolean GRN analysis.

Gustavo Arellano¹, Julián Argil, Eugenio Azpeitia

¹Instituto de Investigaciones en Matemáticas Aplicadas y en Sistemas, Universidad Nacional Autónoma de México, 01000 México D.F., México.

BMC Bioinformatics

|December 24, 2011

Summary

We developed Antelope, a model checker for gene regulatory networks (GRNs), that uses branching time to model complex behaviors like incompletely specified networks and environment interactions. Antelope identifies all states with desired properties, enhancing GRN analysis beyond traditional methods.

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Area of Science:

Computational Biology
Systems Biology
Bioinformatics

Background:

Gene regulatory networks (GRNs) are often modeled using formalisms that incorporate branching time to represent unpredictability.
Branching time in GRN models accounts for phenomena such as asynchrony, incompletely specified behavior, and environmental interactions.
Traditional simulators struggle with the infinite paths generated by branching time, limiting analysis to statistical conclusions.

Purpose of the Study:

To develop a model checker, Antelope, for analyzing and constructing Boolean GRNs.
To extend the application of branching time in GRN modeling beyond asynchrony to include incompletely specified behavior and environment interaction.
To overcome limitations of existing model checkers by reporting all states with a desired property and expressing more complex GRN properties.

Main Methods:

Developed Antelope, a model checker for Boolean GRNs, incorporating branching time for asynchrony, incomplete specifications, and environment interaction.
Utilized a logic extending Computation-Tree Logic (CTL) with hybrid-logic operators to enhance expressiveness.
Applied Antelope to model the Boolean GRN of the Arabidopsis thaliana root stem cell niche.

Main Results:

Antelope successfully models incompletely specified GRNs and environment interactions.
The model checker identifies and reports the complete set of states exhibiting a given property.
Demonstrated the utility of hybrid CTL for expressing complex Boolean GRN properties.

Conclusions:

Antelope offers advantages in modeling incomplete networks and environment interactions in GRNs.
The tool provides comprehensive state-space analysis by reporting all states with desired properties.
Hybrid CTL is effective for representing sophisticated properties of Boolean GRNs.