Name:
s12918-015-0222-7-s1.png
Size:
568.6Kb
Format:
PNG image
Description:
Supplemental files
Type
ArticleDate
2015-11-21Online Publication Date
2015-11-21Print Publication Date
2015-12Permanent link to this record
http://hdl.handle.net/10754/583063
Metadata
Show full item recordAbstract
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 BiologyPublisher
Springer NatureJournal
BMC Systems BiologyPubMed ID
26589144arXiv
1507.08504Additional Links
http://www.biomedcentral.com/1752-0509/9/85Relations
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
Related articles
- Large-scale parameter studies of cell-based models of tissue morphogenesis using CompuCell3D or VirtualLeaf.
- Authors: Palm MM, Merks RM
- Issue date: 2015
- Cellular Potts modeling of complex multicellular behaviors in tissue morphogenesis.
- Authors: Hirashima T, Rens EG, Merks RMH
- Issue date: 2017 Jun
- Computational energetic model of morphogenesis based on multi-agent Cellular Potts Model.
- Authors: Tripodi S, Ballet P, Rodin V
- Issue date: 2010
- Cell-based computational modeling of vascular morphogenesis using Tissue Simulation Toolkit.
- Authors: Daub JT, Merks RM
- Issue date: 2015
- A Julia set model of field-directed morphogenesis: developmental biology and artificial life.
- Authors: Levin M
- Issue date: 1994 Apr