# PyBioNetFit and the Biological Property Specification Language

## TL;DR

PyBioNetFit is a software tool that facilitates parameterization, uncertainty quantification, model checking, and design in systems biology, featuring a novel language for specifying system properties and supporting standard modeling formats.

## Contribution

The paper introduces PyBioNetFit and BPSL, enabling formal property specification and integrated model analysis in systems biology modeling.

## Key findings

- Successfully solved 31 modeling problems including yeast cell cycle
- Demonstrated efficient parallelization on up to 288 cores
- Applied to analyze therapeutic interventions in autophagy signaling

## Abstract

In systems biology modeling, important steps include model parameterization, uncertainty quantification, and evaluation of agreement with experimental observations. To help modelers perform these steps, we developed the software PyBioNetFit. PyBioNetFit is designed for parameterization, and also supports uncertainty quantification, checking models against known system properties, and solving design problems. PyBioNetFit introduces the Biological Property Specification Language (BPSL) for the formal declaration of system properties. BPSL allows qualitative data to be used alone or in combination with quantitative data for parameterization model checking, and design. PyBioNetFit performs parameterization with parallelized metaheuristic optimization algorithms (differential evolution, particle swarm optimization, scatter search) that work directly with existing model definition standards: BioNetGen Language (BNGL) and Systems Biology Markup Language (SBML). We demonstrate PyBioNetFit's capabilities by solving 31 example problems, including the challenging problem of parameterizing a model of cell cycle control in yeast. We benchmark PyBioNetFit's parallelization efficiency on computer clusters, using up to 288 cores. Finally, we demonstrate the model checking and design applications of PyBioNetFit and BPSL by analyzing a model of therapeutic interventions in autophagy signaling.