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    A global sensitivity analysis approach for morphogenesis models

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    Type
    Article
    Authors
    Boas, Sonja E. M.
    Navarro, María
    Merks, Roeland M. H.
    Blom, Joke G.
    KAUST Department
    Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
    Date
    2015-11-21
    Online Publication Date
    2015-11-21
    Print Publication Date
    2015-12
    Permanent link to this record
    http://hdl.handle.net/10754/583063
    
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    Show full item record
    Abstract
    Background Morphogenesis is a developmental process in which cells organize into shapes and patterns. Complex, non-linear and multi-factorial models with images as output are commonly used to study morphogenesis. It is difficult to understand the relation between the uncertainty in the input and the output of such ‘black-box’ models, giving rise to the need for sensitivity analysis tools. In this paper, we introduce a workflow for a global sensitivity analysis approach to study the impact of single parameters and the interactions between them on the output of morphogenesis models. Results To demonstrate the workflow, we used a published, well-studied model of vascular morphogenesis. The parameters of this cellular Potts model (CPM) represent cell properties and behaviors that drive the mechanisms of angiogenic sprouting. The global sensitivity analysis correctly identified the dominant parameters in the model, consistent with previous studies. Additionally, the analysis provided information on the relative impact of single parameters and of interactions between them. This is very relevant because interactions of parameters impede the experimental verification of the predicted effect of single parameters. The parameter interactions, although of low impact, provided also new insights in the mechanisms of in silico sprouting. Finally, the analysis indicated that the model could be reduced by one parameter. Conclusions We propose global sensitivity analysis as an alternative approach to study the mechanisms of morphogenesis. Comparison of the ranking of the impact of the model parameters to knowledge derived from experimental data and from manipulation experiments can help to falsify models and to find the operand mechanisms in morphogenesis. The workflow is applicable to all ‘black-box’ models, including high-throughput in vitro models in which output measures are affected by a set of experimental perturbations.
    Citation
    A global sensitivity analysis approach for morphogenesis models 2015, 9 (1) BMC Systems Biology
    Publisher
    Springer Nature
    Journal
    BMC Systems Biology
    DOI
    10.1186/s12918-015-0222-7
    PubMed ID
    26589144
    arXiv
    1507.08504
    Additional Links
    http://www.biomedcentral.com/1752-0509/9/85
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    Is Supplemented By:
    • [Dataset]
      Boas, S., Jimenez, M. N., Merks, R., & Blom, J. (2015). A global sensitivity analysis approach for morphogenesis models. Figshare. https://doi.org/10.6084/m9.figshare.c.3611270. DOI: 10.6084/m9.figshare.c.3611270 HANDLE: 10754/624129
    ae974a485f413a2113503eed53cd6c53
    10.1186/s12918-015-0222-7
    Scopus Count
    Collections
    Articles; Computer, Electrical and Mathematical Science and Engineering (CEMSE) Division

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