title: Relationship between cancer mutations and parameter sensitivity in Rb pathway.
abstract: It has long been known that formation of all sorts of tumors is largely owing to the genomic variations. Oncogenic mutations are often found focused on one or more important pathways which indicate that it is meaningful to investigate oncogenic mutations and oncogenic mechanisms from the point of view of biological network. Recently, we found that in apoptosis pathway of mammalian cell, mutations that cause large variations on the bifurcation point are more probably oncogenic mutations. Here, we used the Rb-E2F pathway in mammalian cell in response to growth factor as another example to verify this correlation. To conduct this study, nonlinear dynamics equations that describe the behavior of the Rb-E2F pathway was first constructed. Then we identified sensitive parameters which have a great influence on the system's bifurcation point. And we found that the sensitive parameters are highly related to high-frequency oncogenic mutations after comparing the results of parameter sensitivity analysis with profile of known cancer mutations. Moreover, the position of bifurcation point rather than concentration of a certain protein is a better measurement to determine biological network's function. Our results further confirm that nonlinear dynamics analysis of biological networks is an important way to understand oncogenesis. And the analysis method can become a powerful tool to understand and analyze the function of biological network.
authors.affiliation: Condensed Matter Physics, School of Physics, Peking University, Beijing 100871, China.
authors.forename: Xianli
authors.initials: X
authors.lastname: Chen
authors.affiliation: Center for Quantitative Biology and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.affiliation: Center for Quantitative Biology and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Shao
authors.affiliation: Condensed Matter Physics, School of Physics, Peking University, Beijing 100871, China.
authors.forename: Linjie
authors.initials: L
authors.lastname: Zhao
authors.affiliation: The State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing 100871, China.
authors.forename: Haicen
authors.initials: H
authors.lastname: Yue
authors.affiliation: Condensed Matter Physics, School of Physics, Peking University, Beijing 100871, China; Center for Quantitative Biology and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. Electronic address: qi@pku.edu.cn.
authors.forename: Qi
authors.initials: Q
authors.lastname: Ouyang
mesh_terms: D019927:Cyclin E / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D050684:E2F Transcription Factors / Q000378:metabolism; D016193:G1 Phase / Q000235:genetics; D052138:Genes, Neoplasm; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000378:metabolism*; D016196:S Phase / Q000235:genetics; D015398:Signal Transduction
chemical_list: D019927:Cyclin E; D050684:E2F Transcription Factors; D016160:Retinoblastoma Protein; D051357:Cyclin-Dependent Kinase 2
keywords: Oncogenic mutations; Parameters sensitivity analysis