Translation from the Quantified Implicit Process Flow Abstraction in SBGN-PD Diagrams to Bio-PEPA Illustrated on the Cholesterol Pathway

Abstract

For a long time biologists have used visual representations of biochemical networks to gain a quick overview of important structural properties. Recently SBGN, the Systems Biology Graphical Notation, has been developed to standardise the way in which such graphical maps are drawn in order to facilitate the exchange of information. Its qualitative Process Description (SBGN-PD) diagrams are based on an implicit Process Flow Abstraction (PFA) that can also be used to construct quantitative representations, which facilitate automated analyses of the system. Here we explicitly describe the PFA that underpins SBGN-PD and define attributes for SBGN-PD glyphs that make it possible to capture the quantitative details of a biochemical reaction network. Such quantitative details can be used to automatically generate an executable model. To facilitate this, we developed a textual representation for SBGN-PD called "SBGNtext" and implemented SBGNtext2BioPEPA, a tool that demonstrates how Bio-PEPA models can be generated automatically from SBGNtext. Bio-PEPA is a process algebra that was designed for implementing quantitative models of concurrent biochemical reaction systems. The scheme developed here is general and can be easily adapted to other output formalisms. To illustrate the intended workflow, we model the metabolic pathway of the cholesterol synthesis. We use this to compute the statin dosage response of the flux through the cholesterol pathway for different concentrations of the enzyme HMGCR that is inhibited by statin.