320 research outputs found
Reachability in Biochemical Dynamical Systems by Quantitative Discrete Approximation (extended abstract)
In this paper, a novel computational technique for finite discrete
approximation of continuous dynamical systems suitable for a significant class
of biochemical dynamical systems is introduced. The method is parameterized in
order to affect the imposed level of approximation provided that with
increasing parameter value the approximation converges to the original
continuous system. By employing this approximation technique, we present
algorithms solving the reachability problem for biochemical dynamical systems.
The presented method and algorithms are evaluated on several exemplary
biological models and on a real case study.Comment: In Proceedings CompMod 2011, arXiv:1109.104
Analysis of parametric biological models with non-linear dynamics
In this paper we present recent results on parametric analysis of biological
models. The underlying method is based on the algorithms for computing
trajectory sets of hybrid systems with polynomial dynamics. The method is then
applied to two case studies of biological systems: one is a cardiac cell model
for studying the conditions for cardiac abnormalities, and the second is a
model of insect nest-site choice.Comment: In Proceedings HSB 2012, arXiv:1208.315
Analysis of the lactose metabolism in E. coli using sum-of-squares decomposition
We provide a system-theoretic analysis of the mathematical model of lactose induction in E.coli which predicts the level of lactose induction into the cell for specified values of external lactose. Depending on the levels of external lactose and other parameters, the Lac operon is known to have a low steady state in which it is said to be turned off and high steady state where it is said to be turned on. Furthermore, the model has been shown experimentally to exhibit a bi-stable behavior. Using ideas from Lyapunov stability theory and sum-of-squares decomposition, we characterize the reachable state
space for different sets of initial conditions, calculating estimates of the regions of attraction of the biologically relevant equilibria of this system. The changes in the basins of attraction with changes in model parameters can be used to provide biological insight. Specifically, we explain the crucial role played by a small basal transcription rate in the Lac operon. We show that if the basal rate is below a threshold, the region of attraction of the low steady state grows significantly, indicating that system is trapped in the (off) mode, showing the importance of the basal rate of transcription
Towards Personalized Prostate Cancer Therapy Using Delta-Reachability Analysis
Recent clinical studies suggest that the efficacy of hormone therapy for
prostate cancer depends on the characteristics of individual patients. In this
paper, we develop a computational framework for identifying patient-specific
androgen ablation therapy schedules for postponing the potential cancer
relapse. We model the population dynamics of heterogeneous prostate cancer
cells in response to androgen suppression as a nonlinear hybrid automaton. We
estimate personalized kinetic parameters to characterize patients and employ
-reachability analysis to predict patient-specific therapeutic
strategies. The results show that our methods are promising and may lead to a
prognostic tool for personalized cancer therapy.Comment: HSCC 201
Systems Biology of Cancer: A Challenging Expedition for Clinical and Quantitative Biologists
A systems-biology approach to complex disease (such as cancer) is now complementing traditional experience-based approaches, which have typically been invasive and expensive. The rapid progress in biomedical knowledge is enabling the targeting of disease with therapies that are precise, proactive, preventive, and personalized. In this paper, we summarize and classify models of systems biology and model checking tools, which have been used to great success in computational biology and related fields. We demonstrate how these models and tools have been used to study some of the twelve biochemical pathways implicated in but not unique to pancreatic cancer, and conclude that the resulting mechanistic models will need to be further enhanced by various abstraction techniques to interpret phenomenological models of cancer progression
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