Basins of Attraction, Commitment Sets and Phenotypes of Boolean Networks

TL;DR

This paper introduces new methods and software tools for analyzing the basins of attraction and long-term behaviors in Boolean networks, especially in asynchronous and non-deterministic models, with applications in systems biology.

Contribution

It proposes the concepts of commitment sets, markers, and phenotypes for Boolean networks, along with CTL model checking queries and an extension to NuSMV for computing these sets.

Findings

Effective partitioning of state space into commitment sets.

Integration of new modules into PyBoolNet for visualization.

Case study on bladder tumorigenesis demonstrating practical application.

Abstract

The attractors of Boolean networks and their basins have been shown to be highly relevant for model validation and predictive modelling, e.g., in systems biology. Yet there are currently very few tools available that are able to compute and visualise not only attractors but also their basins. In the realm of asynchronous, non-deterministic modeling not only is the repertoire of software even more limited, but also the formal notions for basins of attraction are often lacking. In this setting, the difficulty both for theory and computation arises from the fact that states may be ele- ments of several distinct basins. In this paper we address this topic by partitioning the state space into sets that are committed to the same attractors. These commitment sets can easily be generalised to sets that are equivalent w.r.t. the long-term behaviours of pre-selected nodes which leads us to the notions of markers and phenotypes which we illustrate in a case study on bladder tumorigenesis. For every concept we propose equivalent CTL model checking queries and an extension of the state of the art model checking software NuSMV is made available that is capa- ble of computing the respective sets. All notions are fully integrated as three new modules in our Python package PyBoolNet, including functions for visualising the basins, commitment sets and phenotypes as quotient graphs and pie charts.