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A Modular Workflow for Model Building, Analysis, and Parameter Estimation in Systems Biology and Neuroscience
Department of Neuroscience, Karolinska Institute, 17165, Stockholm, Sweden Graduate Program in Areas of Basic and Applied Biology, Abel Salazar Institute of Biomedical Sciences, University of Porto, Rua Jorge de Viterbo Ferreira 228, 4050-313, Porto, Portugal.
Department of Neuroscience, Karolinska Institute, 17165, Stockholm, Sweden.
KTH, Centra, Science for Life Laboratory, SciLifeLab.
Blue Brain Project, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
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2022 (Engelska)Ingår i: Neuroinformatics, ISSN 1539-2791, E-ISSN 1559-0089, Vol. 20, nr 1, s. 241-259Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Neuroscience incorporates knowledge from a range of scales, from single molecules to brain wide neural networks. Modeling is a valuable tool in understanding processes at a single scale or the interactions between two adjacent scales and researchers use a variety of different software tools in the model building and analysis process. Here we focus on the scale of biochemical pathways, which is one of the main objects of study in systems biology. While systems biology is among the more standardized fields, conversion between different model formats and interoperability between various tools is still somewhat problematic. To offer our take on tackling these shortcomings and by keeping in mind the FAIR (findability, accessibility, interoperability, reusability) data principles, we have developed a workflow for building and analyzing biochemical pathway models, using pre-existing tools that could be utilized for the storage and refinement of models in all phases of development. We have chosen the SBtab format which allows the storage of biochemical models and associated data in a single file and provides a human readable set of syntax rules. Next, we implemented custom-made MATLAB® scripts to perform parameter estimation and global sensitivity analysis used in model refinement. Additionally, we have developed a web-based application for biochemical models that allows simulations with either a network free solver or stochastic solvers and incorporating geometry. Finally, we illustrate convertibility and use of a biochemical model in a biophysically detailed single neuron model by running multiscale simulations in NEURON. Using this workflow, we can simulate the same model in three different simulators, with a smooth conversion between the different model formats, enhancing the characterization of different aspects of the model.

Ort, förlag, år, upplaga, sidor
Springer Nature , 2022. Vol. 20, nr 1, s. 241-259
Nyckelord [en]
Global sensitivity analysis, Interoperability, Multiscale modeling, Parameter estimation, SBtab, Systems biology
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Identifikatorer
URN: urn:nbn:se:kth:diva-312939DOI: 10.1007/s12021-021-09546-3ISI: 000712212400001PubMedID: 34709562Scopus ID: 2-s2.0-85118138813OAI: oai:DiVA.org:kth-312939DiVA, id: diva2:1661839
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QC 20250508

Tillgänglig från: 2022-05-30 Skapad: 2022-05-30 Senast uppdaterad: 2025-05-08Bibliografiskt granskad

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Trpevski, DanielEriksson, OliviaNair, Anu G.Hellgren Kotaleski, JeanetteKramer, Andrei

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Trpevski, DanielEriksson, OliviaNair, Anu G.Hellgren Kotaleski, JeanetteKramer, Andrei
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Science for Life Laboratory, SciLifeLabSeRC - Swedish e-Science Research CentreBeräkningsvetenskap och beräkningsteknik (CST)
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