Parameter sensitivity analysis for a stochastic model of mitochondrial apoptosis pathway.
Understanding how gene alterations induce oncogenesis plays an important role in cancer research and may be instructive for cancer prevention and treatment. We conducted a parameter sensitivity analysis to the mitochondrial apoptosis model. Both a nonlinear bifurcation analysis of the deterministic...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0198579&type=printable |
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| _version_ | 1849715558859145216 |
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| author | Xianli Chen Xiaoguang Li Wei Zhao Tiejun Li Qi Ouyang |
| author_facet | Xianli Chen Xiaoguang Li Wei Zhao Tiejun Li Qi Ouyang |
| author_sort | Xianli Chen |
| collection | DOAJ |
| description | Understanding how gene alterations induce oncogenesis plays an important role in cancer research and may be instructive for cancer prevention and treatment. We conducted a parameter sensitivity analysis to the mitochondrial apoptosis model. Both a nonlinear bifurcation analysis of the deterministic dynamics and energy barrier analysis of the corresponding stochastic models were performed. We found that the parameter sensitivity ranking according to the change of the bifurcation-point locations in deterministic models and the change of the barrier heights from a living to death state of the cell in stochastic models are highly correlated. For the model we considered, in combination with previous knowledge that the parameters significantly affecting the system's bifurcation point are strongly associated with frequently mutated oncogenic genes, we conclude that the energy barrier height can be used as indicator of oncogenesis as well as bifurcation point. We provide a possible mechanism that may help elucidate the logic of cancer initiation from the view of stochastic dynamics and energy landscape. And we show the equivalence of energy barrier height and bifurcation-point location in determining the parameter sensitivity spectrum for the first time. |
| format | Article |
| id | doaj-art-1f812c16c25f4042bf0b2d3acea582f0 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-1f812c16c25f4042bf0b2d3acea582f02025-08-20T03:13:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01136e019857910.1371/journal.pone.0198579Parameter sensitivity analysis for a stochastic model of mitochondrial apoptosis pathway.Xianli ChenXiaoguang LiWei ZhaoTiejun LiQi OuyangUnderstanding how gene alterations induce oncogenesis plays an important role in cancer research and may be instructive for cancer prevention and treatment. We conducted a parameter sensitivity analysis to the mitochondrial apoptosis model. Both a nonlinear bifurcation analysis of the deterministic dynamics and energy barrier analysis of the corresponding stochastic models were performed. We found that the parameter sensitivity ranking according to the change of the bifurcation-point locations in deterministic models and the change of the barrier heights from a living to death state of the cell in stochastic models are highly correlated. For the model we considered, in combination with previous knowledge that the parameters significantly affecting the system's bifurcation point are strongly associated with frequently mutated oncogenic genes, we conclude that the energy barrier height can be used as indicator of oncogenesis as well as bifurcation point. We provide a possible mechanism that may help elucidate the logic of cancer initiation from the view of stochastic dynamics and energy landscape. And we show the equivalence of energy barrier height and bifurcation-point location in determining the parameter sensitivity spectrum for the first time.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0198579&type=printable |
| spellingShingle | Xianli Chen Xiaoguang Li Wei Zhao Tiejun Li Qi Ouyang Parameter sensitivity analysis for a stochastic model of mitochondrial apoptosis pathway. PLoS ONE |
| title | Parameter sensitivity analysis for a stochastic model of mitochondrial apoptosis pathway. |
| title_full | Parameter sensitivity analysis for a stochastic model of mitochondrial apoptosis pathway. |
| title_fullStr | Parameter sensitivity analysis for a stochastic model of mitochondrial apoptosis pathway. |
| title_full_unstemmed | Parameter sensitivity analysis for a stochastic model of mitochondrial apoptosis pathway. |
| title_short | Parameter sensitivity analysis for a stochastic model of mitochondrial apoptosis pathway. |
| title_sort | parameter sensitivity analysis for a stochastic model of mitochondrial apoptosis pathway |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0198579&type=printable |
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