PyBioNetFit and the Biological Property Specification Language

Eshan D. Mitra; Ryan Suderman; Joshua Colvin; Alexander Ionkov; Andrew Hu; Herbert M. Sauro; Richard G. Posner; William S. Hlavacek

iScience (Sep 2019)

PyBioNetFit and the Biological Property Specification Language

Eshan D. Mitra,
Ryan Suderman,
Joshua Colvin,
Alexander Ionkov,
Andrew Hu,
Herbert M. Sauro,
Richard G. Posner,
William S. Hlavacek

Affiliations

Eshan D. Mitra: Theoretical Biology and Biophysics Group, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM, USA
Ryan Suderman: Theoretical Biology and Biophysics Group, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM, USA
Joshua Colvin: Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ, USA
Alexander Ionkov: Theoretical Biology and Biophysics Group, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM, USA
Andrew Hu: Department of Bioengineering, University of Washington, Seattle, WA, USA
Herbert M. Sauro: Department of Bioengineering, University of Washington, Seattle, WA, USA
Richard G. Posner: Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ, USA
William S. Hlavacek: Theoretical Biology and Biophysics Group, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM, USA; Corresponding author

Journal volume & issue: Vol. 19
pp. 1012 – 1036

Abstract

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Summary: 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, which in addition supports checking models against known system properties and solving design problems. PyBioNetFit introduces 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. PyBioNetFit performs parameterization with parallelized metaheuristic optimization algorithms that work directly with existing model definition standards: BioNetGen Language (BNGL) and Systems Biology Markup Language (SBML). We demonstrate PyBioNetFit's capabilities by solving various example problems, including the challenging problem of parameterizing a 153-parameter model of cell cycle control in yeast based on both quantitative and qualitative data. We demonstrate the model checking and design applications of PyBioNetFit and BPSL by analyzing a model of targeted drug interventions in autophagy signaling. : Biological Sciences; Bioinformatics; Systems Biology; Complex Systems; Computer Science; Parallel System Subject Areas: Biological Sciences, Bioinformatics, Systems Biology, Complex Systems, Computer Science, Parallel System

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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