Basins of Attraction, Commitment Sets and Phenotypes of Boolean Networks

Abstract

The attractors of Boolean networks and their basins have been shown to be highly relevant for model validation and predictive modeling, e.g., in systems biology. Yet, there are currently very few tools available that are able to compute and visualize 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 elements 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 generalized to sets that are equivalent w.r.t. the long-term behaviors 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 capable of computing the respective sets. All notions are fully integrated as three new modules in our Python package PyBoolNet, including functions for visualizing the basins, commitment sets, and phenotypes as quotient graphs and pie charts.