Scalable reaction network modeling with automatic validation of consistency in Event-B

Usman Sanwal,Ion Petre,Luigia Petre,Thai Son Hoang

doi:10.1038/s41598-022-05308-6

Abstract

Constructing a large biological model is a difficult, error-prone process. Small errors in writing a part of the model cascade to the system level and their sources are difficult to trace back. In this paper we extend a recent approach based on Event-B, a state-based formal method with refinement as its central ingredient, allowing us to validate for model consistency step-by-step in an automated way. We demonstrate this approach on a model of the heat shock response in eukaryotes and its scalability on a model of the mathsf {ErbB} signaling pathway. All consistency properties of the model were proved automatically with computer support.

Highlights

Constructing a large biological model is a difficult, error-prone process
Event-B19 is a formal method for system modeling, with its original motivations rooted in the specifications of complex software systems
We show that a model of the heat shock response can be described through 17 events, instead of the 57 events in an earlier m odel[18]

Summary

Introduction

Constructing a large biological model is a difficult, error-prone process. Small errors in writing a part of the model cascade to the system level and their sources are difficult to trace back. In this paper we extend a recent approach based on Event-B, a state-based formal method with refinement as its central ingredient, allowing us to validate for model consistency step-by-step in an automated way. We demonstrate this approach on a model of the heat shock response in eukaryotes and its scalability on a model of the ErbB signaling pathway. Event-B19 is a formal method for system modeling, with its original motivations rooted in the specifications of complex software systems It is based on set theory, with refinement at its core, and with a focus on mathematical proofs that the different refinement levels of a model are consistent. All Event-B models discussed in the paper are available at[21]

Methods

Results

Conclusion