Modelling the effect of subcellular mutations on the migration of cells in the colorectal crypt
Abstract Background Many cancers arise from mutations in cells within epithelial tissues. Mutations manifesting at the subcellular level influence the structure and function of the tissue resulting in cancer. Previous work has proposed how cell level properties can lead to mutant cell invasion, but...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-03-01
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| Series: | BMC Bioinformatics |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12859-020-3391-3 |
| _version_ | 1828483391514738688 |
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| author | Lotte B. Romijn Axel A. Almet Chin Wee Tan James M. Osborne |
| author_facet | Lotte B. Romijn Axel A. Almet Chin Wee Tan James M. Osborne |
| author_sort | Lotte B. Romijn |
| collection | DOAJ |
| description | Abstract Background Many cancers arise from mutations in cells within epithelial tissues. Mutations manifesting at the subcellular level influence the structure and function of the tissue resulting in cancer. Previous work has proposed how cell level properties can lead to mutant cell invasion, but has not incorporated detailed subcellular modelling Results We present a framework that allows the straightforward integration and simulation of SBML representations of subcellular dynamics within multiscale models of epithelial tissues. This allows us to investigate the effect of mutations in subcellular pathways on the migration of cells within the colorectal crypt. Using multiple models we find that mutations in APC, a key component in the Wnt signalling pathway, can bias neutral drift and can also cause downward invasion of mutant cells in the crypt. Conclusions Our framework allows us to investigate how subcellular mutations, i.e. knockouts and knockdowns, affect cell-level properties and the resultant migration of cells within epithelial tissues. In the context of the colorectal crypt, we see that mutations in APC can lead directly to mutant cell invasion. |
| first_indexed | 2024-12-11T08:35:48Z |
| format | Article |
| id | doaj.art-008e73f8b8f049b8940c276d4482b8c5 |
| institution | Directory Open Access Journal |
| issn | 1471-2105 |
| language | English |
| last_indexed | 2024-12-11T08:35:48Z |
| publishDate | 2020-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Bioinformatics |
| spelling | doaj.art-008e73f8b8f049b8940c276d4482b8c52022-12-22T01:14:21ZengBMCBMC Bioinformatics1471-21052020-03-0121111610.1186/s12859-020-3391-3Modelling the effect of subcellular mutations on the migration of cells in the colorectal cryptLotte B. Romijn0Axel A. Almet1Chin Wee Tan2James M. Osborne3School of Mathematics and Statistics, University of MelbourneWolfson Centre for Mathematical Biology, Mathematical Institute, University of OxfordPersonalised Oncology Division, The Walter and Eliza Hall Institute of Medical ResearchSchool of Mathematics and Statistics, University of MelbourneAbstract Background Many cancers arise from mutations in cells within epithelial tissues. Mutations manifesting at the subcellular level influence the structure and function of the tissue resulting in cancer. Previous work has proposed how cell level properties can lead to mutant cell invasion, but has not incorporated detailed subcellular modelling Results We present a framework that allows the straightforward integration and simulation of SBML representations of subcellular dynamics within multiscale models of epithelial tissues. This allows us to investigate the effect of mutations in subcellular pathways on the migration of cells within the colorectal crypt. Using multiple models we find that mutations in APC, a key component in the Wnt signalling pathway, can bias neutral drift and can also cause downward invasion of mutant cells in the crypt. Conclusions Our framework allows us to investigate how subcellular mutations, i.e. knockouts and knockdowns, affect cell-level properties and the resultant migration of cells within epithelial tissues. In the context of the colorectal crypt, we see that mutations in APC can lead directly to mutant cell invasion.http://link.springer.com/article/10.1186/s12859-020-3391-3Colorectal cancerCryptMulticellular modellingSBMLChaste |
| spellingShingle | Lotte B. Romijn Axel A. Almet Chin Wee Tan James M. Osborne Modelling the effect of subcellular mutations on the migration of cells in the colorectal crypt BMC Bioinformatics Colorectal cancer Crypt Multicellular modelling SBML Chaste |
| title | Modelling the effect of subcellular mutations on the migration of cells in the colorectal crypt |
| title_full | Modelling the effect of subcellular mutations on the migration of cells in the colorectal crypt |
| title_fullStr | Modelling the effect of subcellular mutations on the migration of cells in the colorectal crypt |
| title_full_unstemmed | Modelling the effect of subcellular mutations on the migration of cells in the colorectal crypt |
| title_short | Modelling the effect of subcellular mutations on the migration of cells in the colorectal crypt |
| title_sort | modelling the effect of subcellular mutations on the migration of cells in the colorectal crypt |
| topic | Colorectal cancer Crypt Multicellular modelling SBML Chaste |
| url | http://link.springer.com/article/10.1186/s12859-020-3391-3 |
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