In silico evolution of signaling networks using rule-based models: bistable response dynamics

TL;DR

This paper demonstrates the use of in silico evolution and rule-based modeling via BioJazz to explore and design cellular signaling networks with bistable response dynamics, providing insights into their structural principles.

Contribution

It introduces BioJazz, a platform for evolving complex signaling networks, and shows how it can be used to design networks with specific bistable response behaviors.

Findings

BioJazz can evolve signaling networks with bistable responses.

Designed networks reveal structural features linked to bistability.

The platform has potential for guiding biological network engineering.

Abstract

One of the ultimate goals in biology is to understand the design principles of biological systems. Such principles, if they exist, can help us better understand complex, natural biological systems and guide the engineering of de novo ones. Towards deciphering design principles, in silico evolution of biological systems with proper abstraction is a promising approach. Here, we demonstrate the application of in silico evolution combined with rule-based modelling for exploring design principles of cellular signaling networks. This application is based on a computational platform, called BioJazz, which allows in silico evolution of signaling networks with unbounded complexity. We provide a detailed introduction to BioJazz architecture and implementation and describe how it can be used to evolve and/or design signaling networks with defined dynamics. For the latter, we evolve signaling networks with switch-like response dynamics and demonstrate how BioJazz can result in new biological insights on network structures that can endow bistable response dynamics. This example also demonstrated both the power of BioJazz in evolving and designing signaling networks and its limitations at the current stage of development.