Global parameter identification of stochastic reaction networks from single trajectories

We consider the problem of inferring the unknown parameters of a stochastic biochemical network model from a single measured time-course of the concentration of some of the involved species. Such measurements are available, e.g., from live-cell fluorescence microscopy in image-based systems biology. In addition, fluctuation time-courses from, e.g., fluorescence correlation spectroscopy provide additional information about the system dynamics that can be used to more robustly infer parameters than when considering only mean concentrations. Estimating model parameters from a single experimental trajectory enables single-cell measurements and quantification of cell--cell variability. We propose a novel combination of an adaptive Monte Carlo sampler, called Gaussian Adaptation, and efficient exact stochastic simulation algorithms that allows parameter identification from single stochastic trajectories. We benchmark the proposed method on a linear and a non-linear reaction network at steady state and during transient phases. In addition, we demonstrate that the present method also provides an ellipsoidal volume estimate of the viable part of parameter space and is able to estimate the physical volume of the compartment in which the observed reactions take place.Comment: Article in print as a book chapter in Springer's "Advances in Systems Biology

Tensor Computation: A New Framework for High-Dimensional Problems in EDA

Many critical EDA problems suffer from the curse of dimensionality, i.e. the very fast-scaling computational burden produced by large number of parameters and/or unknown variables. This phenomenon may be caused by multiple spatial or temporal factors (e.g. 3-D field solvers discretizations and multi-rate circuit simulation), nonlinearity of devices and circuits, large number of design or optimization parameters (e.g. full-chip routing/placement and circuit sizing), or extensive process variations (e.g. variability/reliability analysis and design for manufacturability). The computational challenges generated by such high dimensional problems are generally hard to handle efficiently with traditional EDA core algorithms that are based on matrix and vector computation. This paper presents "tensor computation" as an alternative general framework for the development of efficient EDA algorithms and tools. A tensor is a high-dimensional generalization of a matrix and a vector, and is a natural choice for both storing and solving efficiently high-dimensional EDA problems. This paper gives a basic tutorial on tensors, demonstrates some recent examples of EDA applications (e.g., nonlinear circuit modeling and high-dimensional uncertainty quantification), and suggests further open EDA problems where the use of tensor computation could be of advantage.Comment: 14 figures. Accepted by IEEE Trans. CAD of Integrated Circuits and System