期刊
JOURNAL OF COMPUTATIONAL BIOLOGY
卷 17, 期 3, 页码 325-336出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/cmb.2009.0172
关键词
algorithms; computational molecular biology; stochastic processes
类别
资金
- NSF [CNS 0926181]
The dynamics of biological processes are often modeled as systems of nonlinear ordinary differential equations (ODE). An important feature of nonlinear ODEs is that seemingly minor changes in initial conditions or parameters can lead to radically different behaviors. This is problematic because in general it is never possible to know/measure the precise state of any biological system due to measurement errors. The parameter synthesis problem is to identify sets of parameters (including initial conditions) for which a given system of nonlinear ODEs does not reach a given set of undesirable states. We present an efficient algorithm for solving this problem that combines sensitivity analysis with an efficient search over initial conditions. It scales to high-dimensional models and is exact if the given model is affine. We demonstrate our method on different models of the acute inflammatory response to bacterial infection, and identify initial conditions consistent with three biologically relevant outcomes.
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