MOTIVATION: Parameter estimation is a cornerstone of data-driven modeling in systems biology. Yet, constructing such problems in a reproducible and accessible manner remains challenging. The PEtab format has established itself as a powerful community standard to encode parameter estimation problems, promoting interoperability and reusability. However, its reliance on multiple interlinked files-often edited manually-can introduce inconsistencies, and new users often struggle to navigate them. Here, we present PEtab-GUI, an open-source Python application designed to streamline the creation, editing, and validation of PEtab problems through an intuitive graphical user interface. PEtab-GUI integrates all PEtab components, including SBML models and tabular files, into a single environment with live error checking and customizable defaults. Interactive visualization and simulation capabilities enable users to inspect the relationship between the model and the data. PEtab-GUI lowers the barrier to entry for specifying standardized parameter estimation problems, making dynamic modeling more accessible, especially in educational and interdisciplinary settings. AVAILABILITY AND IMPLEMENTATION: PEtab-GUI is implemented in Python, open-source under a 3-Clause BSD license. The code, designed to be modular and extensible, is hosted on https://github.com/PEtab-dev/PEtab-GUI, available as a Zenodo repository at https://doi.org/10.5281/zenodo.15355752, and can be installed from PyPI.

MOTIVATION: COPASI is a biochemical simulator and model analyzer which has found widespread use in academic research, teaching and beyond. One of COPASI's strengths is its graphical user interface, and this is what most users work with. COPASI also provides a command-line tool. So far, an intuitive scripting interface that allows the creation and documentation of systems biology workflows was missing though. RESULTS: We have developed CoRC, the COPASI R Connector, an R package which provides a high-level scripting interface for COPASI. It closely mirrors the thought process of a (graphical interface) user and should therefore be very easy to use. This allows for complex workflows to be reproducibly scripted, utilizing COPASI's powerful analytic toolset in combination with R's extensive analysis and package ecosystem. AVAILABILITY AND IMPLEMENTATION: CoRC is a free and open-source R package, available via GitHub at https://jpahle.github.io/CoRC/ under the Artistic-2.0 license. SUPPLEMENTARY INFORMATION: We provide tutorial articles as well as several example scripts on the project's website.

Reproducibility and reusability of the results of data-based modeling studies are essential. Yet, there has been-so far-no broadly supported format for the specification of parameter estimation problems in systems biology. Here, we introduce PEtab, a format which facilitates the specification of parameter estimation problems using Systems Biology Markup Language (SBML) models and a set of tab-separated value files describing the observation model and experimental data as well as parameters to be estimated. We already implemented PEtab support into eight well-established model simulation and parameter estimation toolboxes with hundreds of users in total. We provide a Python library for validation and modification of a PEtab problem and currently 20 example parameter estimation problems based on recent studies.

Summary: The Simulation Experiment Description Markup Language (SED-ML) is a standardized format for exchanging simulation studies independently of software tools. We present the SED-ML Web Tools, an online application for creating, editing, simulating and validating SED-ML documents. The Web Tools implement all current SED-ML specifications and, thus, support complex modifications and co-simulation of models in SBML and CellML formats. Ultimately, the Web Tools lower the bar on working with SED-ML documents and help users create valid simulation descriptions. Availability and Implementation: http://sysbioapps.dyndns.org/SED-ML_Web_Tools/ . Contact: [email protected] .

MOTIVATION: Computational modeling is widely used for deepening the understanding of biological processes. Parameterizing models to experimental data needs computationally efficient techniques for parameter estimation. Challenges for parameter estimation include in general the high dimensionality of the parameter space with local minima and in specific for stochastic modeling the intrinsic stochasticity. RESULTS: We implemented the recently suggested multiple shooting for stochastic systems (MSS) objective function for parameter estimation in stochastic models into COPASI. This MSS objective function can be used for parameter estimation in stochastic models but also shows beneficial properties when used for ordinary differential equation models. The method can be applied with all of COPASI's optimization algorithms, and can be used for SBML models as well. AVAILABILITY AND IMPLEMENTATION: The methodology is available in COPASI as of version 4.15.95 and can be downloaded from http://www.copasi.org CONTACT: [email protected] or [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

UNLABELLED: : SBtab is a table-based data format for Systems Biology, designed to support automated data integration and model building. It uses the structure of spreadsheets and defines conventions for table structure, controlled vocabularies and semantic annotations. The format comes with predefined table types for experimental data and SBML-compliant model structures and can easily be customized to cover new types of data. AVAILABILITY AND IMPLEMENTATION: SBtab documents can be created and edited with any text editor or spreadsheet tool. The website www.sbtab.net provides online tools for syntax validation and conversion to SBML and HTML, as well as software for using SBtab in MS Excel, MATLAB and R. The stand-alone Python code contains functions for file parsing, validation, conversion to SBML and HTML and an interface to SQLite databases, to be integrated into Systems Biology workflows. A detailed specification of SBtab, including examples and descriptions of table types and available tools, can be found at www.sbtab.net CONTACT: : [email protected].

BACKGROUND: With the ever increasing use of computational models in the biosciences, the need to share models and reproduce the results of published studies efficiently and easily is becoming more important. To this end, various standards have been proposed that can be used to describe models, simulations, data or other essential information in a consistent fashion. These constitute various separate components required to reproduce a given published scientific result. RESULTS: We describe the Open Modeling EXchange format (OMEX). Together with the use of other standard formats from the Computational Modeling in Biology Network (COMBINE), OMEX is the basis of the COMBINE Archive, a single file that supports the exchange of all the information necessary for a modeling and simulation experiment in biology. An OMEX file is a ZIP container that includes a manifest file, listing the content of the archive, an optional metadata file adding information about the archive and its content, and the files describing the model. The content of a COMBINE Archive consists of files encoded in COMBINE standards whenever possible, but may include additional files defined by an Internet Media Type. Several tools that support the COMBINE Archive are available, either as independent libraries or embedded in modeling software. CONCLUSIONS: The COMBINE Archive facilitates the reproduction of modeling and simulation experiments in biology by embedding all the relevant information in one file. Having all the information stored and exchanged at once also helps in building activity logs and audit trails. We anticipate that the COMBINE Archive will become a significant help for modellers, as the domain moves to larger, more complex experiments such as multi-scale models of organs, digital organisms, and bioengineering.

MOTIVATION: LibSBGN is a software library for reading, writing and manipulating Systems Biology Graphical Notation (SBGN) maps stored using the recently developed SBGN-ML file format. The library (available in C++ and Java) makes it easy for developers to add SBGN support to their tools, whereas the file format facilitates the exchange of maps between compatible software applications. The library also supports validation of maps, which simplifies the task of ensuring compliance with the detailed SBGN specifications. With this effort we hope to increase the adoption of SBGN in bioinformatics tools, ultimately enabling more researchers to visualize biological knowledge in a precise and unambiguous manner. AVAILABILITY AND IMPLEMENTATION: Milestone 2 was released in December 2011. Source code, example files and binaries are freely available under the terms of either the LGPL v2.1+ or Apache v2.0 open source licenses from http://libsbgn.sourceforge.net. CONTACT: [email protected].

This FAIRsharing record describes: The MIASE Guidelines, initiated by the BioModels.net effort, are a community effort to identify the Minimal Information About a Simulation Experiment, necessary to enable the reproducible simulation experiments. Consequently, the MIASE Guidelines list the information that a modeller needs to provide to enable the execution and reproduction of a numerical simulation experiment, derived from a given set of quantitative models. MIASE is a set of guidelines suitable for use with any structured format for simulation experiments. As such, MIASE is designed to help modelers and software tools to exchange their simulation settings and to foster collaboration.

MOTIVATION: The SBML Render Extension enables coloring and shape information of biochemical models to be stored in the Systems Biology Markup Language (SBML). Rendering of this stored graphical information in a portable and well supported system such as TeX would be useful for researchers preparing documentation and presentations. In addition, since the Render Extension is not yet supported by many applications, it is helpful for such rendering functionality be extended to the more popular CellDesigner annotation as well. RESULTS: SBML2TikZ supports automatic generation of graphics for biochemical models in the popular TeX typesetting system. The library generates a script of TeX macro commands for the vector graphics languages PGF/TikZ that can be compiled into scalable vector graphics described in a model. AVAILABILITY: Source code, documentation and compiled binaries for the SBML2TikZ library can be found at http://www.sbml2tikz.org. In addition, a web application is available at http://www.sys-bio.org/layout

MOTIVATION: Model exchange in systems and synthetic biology has been standardized for computers with the Systems Biology Markup Language (SBML) and CellML, but specialized software is needed for the generation of models in these formats. Text-based model definition languages allow researchers to create models simply, and then export them to a common exchange format. Modular languages allow researchers to create and combine complex models more easily. We saw a use for a modular text-based language, together with a translation library to allow other programs to read the models as well. SUMMARY: The Antimony language provides a way for a researcher to use simple text statements to create, import, and combine biological models, allowing complex models to be built from simpler models, and provides a special syntax for the creation of modular genetic networks. The libAntimony library allows other software packages to import these models and convert them either to SBML or their own internal format. AVAILABILITY: The Antimony language specification and the libAntimony library are available under a BSD license from http://antimony.sourceforge.net/.

MOTIVATION: Simulations are an essential tool when analyzing biochemical networks. Researchers and developers seeking to refine simulation tools or develop new ones would benefit greatly from being able to compare their simulation results. SUMMARY: We present an approach to compare simulation results between several SBML capable simulators and provide a website for the community to share simulation results. AVAILABILITY: The website with simulation results and additional material can be found under: http://sys-bio.org/sbwWiki/compare. The software used to generate the simulation results is available on the website for download.

MOTIVATION: Researchers studying large or complex biochemical networks would benefit from the ability to automatically create lucid visualizations and store them in a portable and widely accepted format. SUMMARY: Two modules, SBMLSupportLayout and SBWAutoLayout, support reading, creating, manipulating and writing layout information for biochemical models. SBMLSupportLayout can read, update, add and render model layout information. SBWAutoLayout can automatically layout models, graphically manipulate model layout and generate layout information for models without layout information. AVAILABILITY: SBMLSupportLayout and SBWAutoLayout are distributed with the Systems Biology Workbench (SBW), which can be downloaded from http://www.sys-bio.org. Additionally, their visualization and layout capabilities are available online at http://www.sys-bio.org/Layout. Both modules run on Win32, Linux and the Mac OS X version is forthcoming.

MOTIVATION: Biochemical networks often yield interesting behavior such as switching, oscillation and chaotic dynamics. This article describes a tool that is capable of searching for bifurcation points in arbitrary ODE-based reaction networks by directing the user to regions in the parameter space, where such interesting dynamical behavior can be observed. RESULTS: We have implemented a genetic algorithm that searches for Hopf bifurcations, turning points and bistable switches. The software is implemented as a Systems Biology Workbench (SBW) enabled module and accepts the standard SBML model format. The interface permits a user to choose the parameters to be searched, admissible parameter ranges, and the nature of the bifurcation to be sought. The tool will return the parameter values for the model for which the particular behavior is observed. AVAILABILITY: The software, tutorial manual and test models are available for download at the following website: http:/www.sys-bio.org/ under the bifurcation link. The software is an open source and licensed under BSD.