Parameter-free methods distinguish Wnt pathway models and guide design of experiments
The canonical Wnt signaling pathway, mediated by β-catenin, is crucially involved in development, adult stem cell tissue maintenance, and a host of diseases including cancer. We analyze existing mathematical models of Wnt and compare them to a new Wnt signaling model that targets spatial localizatio...
| Main Authors: | , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
National Academy of Sciences
2015
|
| _version_ | 1797093822221516800 |
|---|---|
| author | MacLean, A Rosen, Z Byrne, H Harrington, H |
| author_facet | MacLean, A Rosen, Z Byrne, H Harrington, H |
| author_sort | MacLean, A |
| collection | OXFORD |
| description | The canonical Wnt signaling pathway, mediated by β-catenin, is crucially involved in development, adult stem cell tissue maintenance, and a host of diseases including cancer. We analyze existing mathematical models of Wnt and compare them to a new Wnt signaling model that targets spatial localization; our aim is to distinguish between the models and distill biological insight from them. Using Bayesian methods we infer parameters for each model from mammalian Wnt signaling data and find that all models can fit this time course. We appeal to algebraic methods (concepts from chemical reaction network theory and matroid theory) to analyze the models without recourse to specific parameter values. These approaches provide insight into aspects of Wnt regulation: the new model, via control of shuttling and degradation parameters, permits multiple stable steady states corresponding to stem-like vs. committed cell states in the differentiation hierarchy. Our analysis also identifies groups of variables that should be measured to fully characterize and discriminate between competing models, and thus serves as a guide for performing minimal experiments for model comparison. |
| first_indexed | 2024-03-07T04:05:42Z |
| format | Journal article |
| id | oxford-uuid:c611a3d1-fd8b-4cee-ab03-ecd1be304338 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:05:42Z |
| publishDate | 2015 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | oxford-uuid:c611a3d1-fd8b-4cee-ab03-ecd1be3043382022-03-27T06:35:37ZParameter-free methods distinguish Wnt pathway models and guide design of experimentsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c611a3d1-fd8b-4cee-ab03-ecd1be304338EnglishSymplectic Elements at OxfordNational Academy of Sciences2015MacLean, ARosen, ZByrne, HHarrington, HThe canonical Wnt signaling pathway, mediated by β-catenin, is crucially involved in development, adult stem cell tissue maintenance, and a host of diseases including cancer. We analyze existing mathematical models of Wnt and compare them to a new Wnt signaling model that targets spatial localization; our aim is to distinguish between the models and distill biological insight from them. Using Bayesian methods we infer parameters for each model from mammalian Wnt signaling data and find that all models can fit this time course. We appeal to algebraic methods (concepts from chemical reaction network theory and matroid theory) to analyze the models without recourse to specific parameter values. These approaches provide insight into aspects of Wnt regulation: the new model, via control of shuttling and degradation parameters, permits multiple stable steady states corresponding to stem-like vs. committed cell states in the differentiation hierarchy. Our analysis also identifies groups of variables that should be measured to fully characterize and discriminate between competing models, and thus serves as a guide for performing minimal experiments for model comparison. |
| spellingShingle | MacLean, A Rosen, Z Byrne, H Harrington, H Parameter-free methods distinguish Wnt pathway models and guide design of experiments |
| title | Parameter-free methods distinguish Wnt pathway models and guide design of experiments |
| title_full | Parameter-free methods distinguish Wnt pathway models and guide design of experiments |
| title_fullStr | Parameter-free methods distinguish Wnt pathway models and guide design of experiments |
| title_full_unstemmed | Parameter-free methods distinguish Wnt pathway models and guide design of experiments |
| title_short | Parameter-free methods distinguish Wnt pathway models and guide design of experiments |
| title_sort | parameter free methods distinguish wnt pathway models and guide design of experiments |
| work_keys_str_mv | AT macleana parameterfreemethodsdistinguishwntpathwaymodelsandguidedesignofexperiments AT rosenz parameterfreemethodsdistinguishwntpathwaymodelsandguidedesignofexperiments AT byrneh parameterfreemethodsdistinguishwntpathwaymodelsandguidedesignofexperiments AT harringtonh parameterfreemethodsdistinguishwntpathwaymodelsandguidedesignofexperiments |