A toolbox for discrete modelling of cell signalling dynamics

Abstract

In an age where the volume of data regarding biological systems exceeds our ability to analyse it, many researchers are looking towards systems biology and computational modelling to help unravel the complexities of gene and protein regulatory networks. In particular, the use of discrete modelling allows generation of signalling networks in the absence of full quantitative descriptions of systems, which are necessary for ordinary differential equation (ODE) models. In order to make such techniques more accessible to mainstream researchers, tools such as the BioModelAnalyzer (BMA) have been developed to provide a user-friendly graphical interface for discrete modelling of biological systems. Here we use the BMA to build a library of discrete target functions of known canonical molecular interactions, translated from ordinary differential equations (ODEs). We then show that these BMA target functions can be used to reconstruct complex networks, which can correctly predict many known genetic perturbations. This new library supports the accessibility ethos behind the creation of BMA, providing a toolbox for the construction of complex cell signalling models without the need for extensive experience in computer programming or mathematical modelling, and allows for construction and simulation of complex biological systems with only small amounts of quantitative data.

HOXA9 has the hallmarks of a biological switch with implications in blood cancers

“…To address this question, we constructed a computational network model in a multistep process. In order to reproduce the branching in MPN patients, the underlying network of gene interactions must include genes that are sensitive to the mutation order 29 . This requires that parts of the network act a switch, capable of storing “memory” of previous events.…”

Verifiable biology

“…BIOMODELANALYZER [159] is a web-based toolset developed for the modelling and analysis of gene and protein interaction networks. Based on the Qualitative Networks formalism, users can graphically draw biological models manually or using a built-in library.…”

Constructing and Analyzing Computational Models of Cell Signaling with BioModelAnalyzer

“…Tyson, Chen, and Novak (2003) characterized these models for continuous modeling in detail. Subsequently, we established that executable models were similarly expressive, and integrated a set of motifs into the tool itself (Paterson et al, 2018). Such motifs aid the construction of complex networks by providing a set of fundamental cellular patterns that can be directly integrated into the network.…”

“…In this tutorial, we will revisit the cell cycle model from Paterson et al (2018), demonstrating how a simplified version can be constructed out of available motifs. Here you should follow the instructions to build the model using the steps described.…”

“…construct and analyze models while avoiding use of the CLI as much as possible. The tutorials introduce key, distinguishing features of the approach and tool-developing models and specifications of varying complexity using the graphical linear temporal logic (LTL) editor (Ahmed et al, 2017;Claessen et al, 2013) and the motif library (a collection of pre-built mini-networks, encoding key biological functions; Paterson et al, 2018). BMA is open source (MIT license) and is run as a publicly available web service for all users.…”