A compartmental model of the cAMP/PKA/MAPK pathway in Bio-PEPA

TL;DR

This paper models the cAMP/PKA/MAPK pathway using Bio-PEPA, emphasizing the importance of compartments in biochemical systems, and validates the model through stochastic simulations and analysis of feedback mechanisms.

Contribution

It introduces a multi-compartmental Bio-PEPA model of the pathway, validated against ODE models, and explores pathway regulation through computational experiments.

Findings

Model accurately reproduces known pathway dynamics.

Feedback loop modifications significantly affect pathway behavior.

Compartmental modeling enhances understanding of biochemical regulation.

Abstract

The vast majority of biochemical systems involve the exchange of information between different compartments, either in the form of transportation or via the intervention of membrane proteins which are able to transmit stimuli between bordering compartments. The correct quantitative handling of compartments is, therefore, extremely important when modelling real biochemical systems. The Bio-PEPA process algebra is equipped with the capability of explicitly defining quantitative information such as compartment volumes and membrane surface areas. Furthermore, the recent development of the Bio-PEPA Eclipse Plug-in allows us to perform a correct stochastic simulation of multi-compartmental models. Here we present a Bio-PEPA compartmental model of the cAMP/PKA/MAPK pathway. We analyse the system using the Bio-PEPA Eclipse Plug-in and we show the correctness of our model by comparison with an existing ODE model. Furthermore, we perform computational experiments in order to investigate certain properties of the pathway. Specifically, we focus on the system response to the inhibition and strengthening of feedback loops and to the variation in the activity of key pathway reactions and we observe how these modifications affect the behaviour of the pathway. These experiments are useful to understand the control and regulatory mechanisms of the system.