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A scalable, open-source implementation of a large-scale mechanistic model for single cell proliferation and death signaling
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Department of Chemical & Biomolecular Engineering, Clemson University, Clemson, SC, USA.ORCID iD: 0000-0003-3663-3646
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2022 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 13, no 1, article id 3555Article in journal (Refereed) Published
Abstract [en]

Abstract Mechanistic models of how single cells respond to different perturbations can help integrate disparate big data sets or predict response to varied drug combinations. However, the construction and simulation of such models have proved challenging. Here, we developed a python-based model creation and simulation pipeline that converts a few structured text files into an SBML standard and is high-performance- and cloud-computing ready. We applied this pipeline to our large-scale, mechanistic pan-cancer signaling model (named SPARCED) and demonstrate it by adding an IFNγ pathway submodel. We then investigated whether a putative crosstalk mechanism could be consistent with experimental observations from the LINCS MCF10A Data Cube that IFNγ acts as an anti-proliferative factor. The analyses suggested this observation can be explained by IFNγ-induced SOCS1 sequestering activated EGF receptors. This work forms a foundational recipe for increased mechanistic model-based data integration on a single-cell level, an important building block for clinically-predictive mechanistic models.

Place, publisher, year, edition, pages
Nature Publishing Group, 2022. Vol. 13, no 1, article id 3555
National Category
Bioinformatics and Systems Biology
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URN: urn:nbn:se:umu:diva-218249DOI: 10.1038/s41467-022-31138-1ISI: 000814343700004PubMedID: 35729113Scopus ID: 2-s2.0-85132312886OAI: oai:DiVA.org:umu-218249DiVA, id: diva2:1820885
Available from: 2023-12-19 Created: 2023-12-19 Last updated: 2024-04-16Bibliographically approved

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Erdem, Cemal

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CiteExportLink to record
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Citation style
  • apa
  • ieee
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More styles
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  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
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  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf