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Correlation between oncogenic mutations and parameter sensitivity of the apoptosis pathway model.
Jia Chen1, Haicen Yue2, Qi Ouyang2
1Center for Quantitative Biology and Peking-Tsinghua Center for Life Sciences at Peking University, Beijing, China.
Plos Computational Biology
|January 28, 2014
Summary
Cancer mutations concentrate in key biological pathways, suggesting a link to regulatory network dynamics. This study links oncogenic mutations to parameter sensitivity in DNA damage-induced apoptosis networks, identifying critical network points associated with cancer development.
Area of Science:
- Oncogenesis research
- Systems biology
- Cancer genomics
Background:
- Oncogenic mutations are concentrated in a few core biological pathways.
- Oncogenic mechanisms are linked to the dynamics of biological regulatory networks.
Purpose of the Study:
- To investigate the relationship between oncogenic mutations in different biological pathways and the parameter sensitivity of corresponding regulatory networks.
- To test the hypothesis that parameter sensitivity is a key factor in oncogenesis.
Main Methods:
- Construction of the regulatory network governing the DNA damage-induced apoptotic pathway.
- Translation of the network into dynamic equations.
- Sensitivity analysis of network parameters and comparison with cancer gene mutation spectra.
Main Results:
- Parameters significantly affecting the bifurcation point of the apoptosis network correspond to high-frequency oncogenic mutations.
- The position of the bifurcation point is a more effective measure of biological network functionality than gene expression levels.
Conclusions:
- Parameter sensitivity analysis of biological networks provides insights into oncogenesis.
- Systems-level analysis is more suitable for understanding biological networks in cancer research than studying individual genes or proteins.
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