TY - GEN
T1 - Robustness analysis of cellular systems for in silico drug discovery
AU - Perumal, Thanneer Malai
AU - Wu, Yan
AU - Gunawan, Rudiyanto
PY - 2008
Y1 - 2008
N2 - Biological robustness has been recognized as a fundamental organizational principle in cellular behavior. The understanding of robustness trade-off in biology has significant implications in the drug discovery research. Some diseases such as cancer can hijack cellular robustness complicating their treatment. Most of the published robustness analyses in systems biology relate this property to the output parametric sensitivity. A new analysis is proposed in which the sensitivities are evaluated for perturbations on the system states rather than on the model parameters. The result of this analysis can be directly validated in experiments, and further used in the drug discovery research to understand drug effects, to optimize drug dosing and timing, and to identify potential molecules as drug targets. The application to a model of cell death regulation shows the biological insights offered by this analysis.
AB - Biological robustness has been recognized as a fundamental organizational principle in cellular behavior. The understanding of robustness trade-off in biology has significant implications in the drug discovery research. Some diseases such as cancer can hijack cellular robustness complicating their treatment. Most of the published robustness analyses in systems biology relate this property to the output parametric sensitivity. A new analysis is proposed in which the sensitivities are evaluated for perturbations on the system states rather than on the model parameters. The result of this analysis can be directly validated in experiments, and further used in the drug discovery research to understand drug effects, to optimize drug dosing and timing, and to identify potential molecules as drug targets. The application to a model of cell death regulation shows the biological insights offered by this analysis.
KW - Cellular, metabolic, cardiovascular, neurosystems
KW - Dynamics and control
KW - Kinetic modelling and control of biological systems
UR - https://www.scopus.com/pages/publications/79961017716
U2 - 10.3182/20080706-5-KR-1001.1365
DO - 10.3182/20080706-5-KR-1001.1365
M3 - Conference contribution
AN - SCOPUS:79961017716
SN - 9783902661005
T3 - IFAC Proceedings Volumes (IFAC-PapersOnline)
BT - Proceedings of the 17th World Congress, International Federation of Automatic Control, IFAC
T2 - 17th World Congress, International Federation of Automatic Control, IFAC
Y2 - 6 July 2008 through 11 July 2008
ER -