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Research article
Modelling the effect of subcellular mutations on the migration of cells in the colorectal crypt
James Osborne
University Of Melbourne
Corresponding Author
ORCiD: https://orcid.org/0000-0002-5622-0104
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at BMC Bioinformatics.
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.
Keywords
Colorectal Cancer; Crypt; Multicellular Modelling; SBML; Chaste
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CURRENT STATUS: Published
Published
On 03 Mar, 2020
No community comments so far
Editorial decision: Accept
On 21 Jan, 2020
Review #1 received
Received 19 Jan, 2020
Reviewer #1 agreed
On 17 Jan, 2020
Editor assigned
On 15 Jan, 2020
Reviewers invited
Invitations sent on 15 Jan, 2020
Submission checks complete
On 14 Jan, 2020
Editor invited
On 14 Jan, 2020
Version 2
Posted 19 Nov, 2019
No comments provided
Editorial decision: Major revision
On 20 Dec, 2019
Review #2 received
Received 19 Dec, 2019
Review #1 received
Received 29 Nov, 2019
Reviewer #2 agreed
On 20 Nov, 2019
Reviewer #1 agreed
On 16 Nov, 2019
Reviewers invited
Invitations sent on 15 Nov, 2019
Editor assigned
On 13 Nov, 2019
Submission checks complete
On 12 Nov, 2019
Editor invited
On 12 Nov, 2019
No comments provided
Editorial decision: Major revision
On 16 Sep, 2019
Review #1 received
Received 26 Aug, 2019
Review #2 received
Received 26 Aug, 2019
Reviewer #1 agreed
On 21 Aug, 2019
Reviewer #2 agreed
On 21 Aug, 2019
Reviewers invited
Invitations sent on 12 Aug, 2019
Submission checks complete
On 04 Jun, 2019
Editor invited
On 29 May, 2019
Editor assigned
On 29 May, 2019
First submitted
On 28 May, 2019
Metrics
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HTML Views: ...
Subject Areas
Bioinformatics
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This preprint is under consideration at BMC Bioinformatics. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Modelling the effect of subcellular mutations on the migration of cells in the colorectal crypt
James Osborne
University Of Melbourne
Corresponding Author
ORCiD: https://orcid.org/0000-0002-5622-0104
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Published
On 03 Mar, 2020
No community comments so far
Editorial decision: Accept
On 21 Jan, 2020
Review #1 received
Received 19 Jan, 2020
Reviewer #1 agreed
On 17 Jan, 2020
Editor assigned
On 15 Jan, 2020
Reviewers invited
Invitations sent on 15 Jan, 2020
Submission checks complete
On 14 Jan, 2020
Editor invited
On 14 Jan, 2020
Version 2
Posted 19 Nov, 2019
No comments provided
Editorial decision: Major revision
On 20 Dec, 2019
Review #2 received
Received 19 Dec, 2019
Review #1 received
Received 29 Nov, 2019
Reviewer #2 agreed
On 20 Nov, 2019
Reviewer #1 agreed
On 16 Nov, 2019
Reviewers invited
Invitations sent on 15 Nov, 2019
Editor assigned
On 13 Nov, 2019
Submission checks complete
On 12 Nov, 2019
Editor invited
On 12 Nov, 2019
No comments provided
Editorial decision: Major revision
On 16 Sep, 2019
Review #1 received
Received 26 Aug, 2019
Review #2 received
Received 26 Aug, 2019
Reviewer #1 agreed
On 21 Aug, 2019
Reviewer #2 agreed
On 21 Aug, 2019
Reviewers invited
Invitations sent on 12 Aug, 2019
Submission checks complete
On 04 Jun, 2019
Editor invited
On 29 May, 2019
Editor assigned
On 29 May, 2019
First submitted
On 28 May, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Bioinformatics
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at BMC Bioinformatics.
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.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Due to technical limitations, full-text HTML conversion of this manuscript could not be completed. However, the manuscript can be downloaded and accessed as a PDF.