Reconstruction and logical modeling of glucose repression signaling pathways in Saccharomyces cerevisiae
Background: In the yeast Saccharomyces cerevisiae, the presence of high levels of glucose leads to an array of down-regulatory effects known as glucose repression. This process is complex due to the presence of feedback loops and crosstalk between different pathways, complicating the use of intuitiv...
| Main Authors: | , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
BioMed Central Ltd
2010
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| Online Access: | http://hdl.handle.net/1721.1/58761 |
| _version_ | 1826210042644267008 |
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| author | Oliveira, Ana Paula Nielsen, Jens Kromann Christensen, Tobias S. |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Oliveira, Ana Paula Nielsen, Jens Kromann Christensen, Tobias S. |
| author_sort | Oliveira, Ana Paula |
| collection | MIT |
| description | Background: In the yeast Saccharomyces cerevisiae, the presence of high levels of glucose leads to an array of down-regulatory effects known as glucose repression. This process is complex due to the presence of feedback loops and crosstalk between different pathways, complicating the use of intuitive approaches to analyze the system. Results: We established a logical model of yeast glucose repression, formalized as a hypergraph. The model was constructed based on verified regulatory interactions and it includes 50 gene transcripts, 22 proteins, 5 metabolites and 118 hyperedges. We computed the logical steady states of all nodes in the network in order to simulate wildtype and deletion mutant responses to different sugar availabilities. Evaluation of the model predictive power was achieved by comparing changes in the logical state of gene nodes with transcriptome data. Overall, we observed 71% true predictions, and analyzed sources of errors and discrepancies for the remaining. Conclusion: Though the binary nature of logical (Boolean) models entails inherent limitations, our model constitutes a primary tool for storing regulatory knowledge, searching for incoherencies in hypotheses and evaluating the effect of deleting regulatory elements involved in glucose repression. |
| first_indexed | 2024-09-23T14:40:35Z |
| format | Article |
| id | mit-1721.1/58761 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:40:35Z |
| publishDate | 2010 |
| publisher | BioMed Central Ltd |
| record_format | dspace |
| spelling | mit-1721.1/587612022-10-01T21:59:35Z Reconstruction and logical modeling of glucose repression signaling pathways in Saccharomyces cerevisiae Oliveira, Ana Paula Nielsen, Jens Kromann Christensen, Tobias S. Massachusetts Institute of Technology. Department of Chemical Engineering Christensen, Tobias S. Background: In the yeast Saccharomyces cerevisiae, the presence of high levels of glucose leads to an array of down-regulatory effects known as glucose repression. This process is complex due to the presence of feedback loops and crosstalk between different pathways, complicating the use of intuitive approaches to analyze the system. Results: We established a logical model of yeast glucose repression, formalized as a hypergraph. The model was constructed based on verified regulatory interactions and it includes 50 gene transcripts, 22 proteins, 5 metabolites and 118 hyperedges. We computed the logical steady states of all nodes in the network in order to simulate wildtype and deletion mutant responses to different sugar availabilities. Evaluation of the model predictive power was achieved by comparing changes in the logical state of gene nodes with transcriptome data. Overall, we observed 71% true predictions, and analyzed sources of errors and discrepancies for the remaining. Conclusion: Though the binary nature of logical (Boolean) models entails inherent limitations, our model constitutes a primary tool for storing regulatory knowledge, searching for incoherencies in hypotheses and evaluating the effect of deleting regulatory elements involved in glucose repression. Fundação para a Ciência e a Tecnologia Portuguese Ministry of Science and Technology (grant no. SFRH/BD/12435/2003) 2010-09-29T18:15:42Z 2010-09-29T18:15:42Z 2009-01 2008-09 2010-09-03T16:22:47Z Article http://purl.org/eprint/type/JournalArticle 1752-0509 http://hdl.handle.net/1721.1/58761 BMC Systems Biology. 2009 Jan 14;3(1):7 19144179 en http://dx.doi.org/10.1186/1752-0509-3-7 BMC Systems Biology Creative Commons Attribution http://creativecommons.org/licenses/by/2.0 Christensen et al.; licensee BioMed Central Ltd. application/pdf BioMed Central Ltd BioMed Central Ltd |
| spellingShingle | Oliveira, Ana Paula Nielsen, Jens Kromann Christensen, Tobias S. Reconstruction and logical modeling of glucose repression signaling pathways in Saccharomyces cerevisiae |
| title | Reconstruction and logical modeling of glucose repression signaling pathways in Saccharomyces cerevisiae |
| title_full | Reconstruction and logical modeling of glucose repression signaling pathways in Saccharomyces cerevisiae |
| title_fullStr | Reconstruction and logical modeling of glucose repression signaling pathways in Saccharomyces cerevisiae |
| title_full_unstemmed | Reconstruction and logical modeling of glucose repression signaling pathways in Saccharomyces cerevisiae |
| title_short | Reconstruction and logical modeling of glucose repression signaling pathways in Saccharomyces cerevisiae |
| title_sort | reconstruction and logical modeling of glucose repression signaling pathways in saccharomyces cerevisiae |
| url | http://hdl.handle.net/1721.1/58761 |
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