Repairing Boolean logical models from time-series data using Answer Set Programming

Abstract

Abstract Background Boolean models of biological signalling-regulatory networks are increasingly used to formally describe and understand complex biological processes. These models may become inconsistent as new data become available and need to be repaired. In the past, the focus has been shed on the inference of (classes of) models given an interaction network and time-series data sets. However, repair of existing models against new data is still in its infancy, where the process is still manually performed and therefore slow and prone to errors. Results In this work, we propose a method with an associated tool to suggest repairs over inconsistent Boolean models, based on a set of atomic repair operations. Answer Set Programming is used to encode the minimal repair problem as a combinatorial optimization problem. In particular, given an inconsistent model, the tool provides the minimal repairs that render the model capable of generating dynamics coherent with a (set of) time-series data set(s), considering either a synchronous or an asynchronous updating scheme. Conclusions The method was validated using known biological models from different species, as well as synthetic models obtained from randomly generated networks. We discuss the method’s limitations regarding each of the updating schemes and the considered minimization algorithm.

Keywords

• Biological regulatory networks
• Boolean functions
• Model repair
• (A)synchronous dynamics
• Answer Set Programming