A global sensitivity analysis approach for morphogenesis models

Handle URI:
http://hdl.handle.net/10754/583063
Title:
A global sensitivity analysis approach for morphogenesis models
Authors:
Boas, Sonja E. M.; Navarro, María; Merks, Roeland M. H.; Blom, Joke G.
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.
KAUST Department:
Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Citation:
A global sensitivity analysis approach for morphogenesis models 2015, 9 (1) BMC Systems Biology
Publisher:
Springer Science + Business Media
Journal:
BMC Systems Biology
Issue Date:
21-Nov-2015
DOI:
10.1186/s12918-015-0222-7
Type:
Article
ISSN:
1752-0509
Is Supplemented By:
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:http://hdl.handle.net/10754/624129
Additional Links:
http://www.biomedcentral.com/1752-0509/9/85
Appears in Collections:
Articles; Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorBoas, Sonja E. M.en
dc.contributor.authorNavarro, Maríaen
dc.contributor.authorMerks, Roeland M. H.en
dc.contributor.authorBlom, Joke G.en
dc.date.accessioned2015-12-01T13:46:45Zen
dc.date.available2015-12-01T13:46:45Zen
dc.date.issued2015-11-21en
dc.identifier.citationA global sensitivity analysis approach for morphogenesis models 2015, 9 (1) BMC Systems Biologyen
dc.identifier.issn1752-0509en
dc.identifier.doi10.1186/s12918-015-0222-7en
dc.identifier.urihttp://hdl.handle.net/10754/583063en
dc.description.abstractBackground 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.en
dc.language.isoenen
dc.publisherSpringer Science + Business Mediaen
dc.relation.urlhttp://www.biomedcentral.com/1752-0509/9/85en
dc.rightsThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.en
dc.subjectMorphogenesisen
dc.subjectVascular network developmenten
dc.subjectComputational modelingen
dc.subjectCellular Potts modelen
dc.subjectGlobal sensitivity analysisen
dc.subjectSobol’ indicesen
dc.subjectPolynomial chaos expansionen
dc.titleA global sensitivity analysis approach for morphogenesis modelsen
dc.typeArticleen
dc.contributor.departmentComputer, Electrical and Mathematical Sciences and Engineering (CEMSE) Divisionen
dc.identifier.journalBMC Systems Biologyen
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionLife Sciences, CWI, Science Park 123, Amsterdam 1098XG, The Netherlandsen
dc.contributor.institutionMathematical Institute, University of Leiden, Niels Bohrweg 1, Leiden 2333CA, The Netherlandsen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorNavarro, Maríaen
dc.relation.isSupplementedByBoas, 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.3611270en
dc.relation.isSupplementedByDOI:10.6084/m9.figshare.c.3611270en
dc.relation.isSupplementedByHANDLE:http://hdl.handle.net/10754/624129en
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