Robust filtering for gene expression time series data with variance constraints

This is the post print version of the article. The official published version can be obtained from the link below - Copyright 2007 Taylor & Francis Ltd.In this paper, an uncertain discrete-time stochastic system is employed to represent a model for gene regulatory networks from time series data. A robust variance-constrained filtering problem is investigated for a gene expression model with stochastic disturbances and norm-bounded parameter uncertainties, where the stochastic perturbation is in the form of a scalar Gaussian white noise with constant variance and the parameter uncertainties enter both the system matrix and the output matrix. The purpose of the addressed robust filtering problem is to design a linear filter such that, for the admissible bounded uncertainties, the filtering error system is Schur stable and the individual error variance is less than a prespecified upper bound. By using the linear matrix inequality (LMI) technique, sufficient conditions are first derived for ensuring the desired filtering performance for the gene expression model. Then the filter gain is characterized in terms of the solution to a set of LMIs, which can easily be solved by using available software packages. A simulation example is exploited for a gene expression model in order to demonstrate the effectiveness of the proposed design procedures.This work was supported in part by the Engineering and Physical Sciences Research Council (EPSRC) of the UK under Grants GR/S27658/01 and EP/C524586/1, the Biotechnology and Biological Sciences Research Council (BBSRC) of the UK under Grants BB/C506264/1 and 100/EGM17735, the Nuffield Foundation of the UK under Grant NAL/00630/G, and the Alexander von Humboldt Foundation of Germany

Filtering for nonlinear genetic regulatory networks with stochastic disturbances

In this paper, the filtering problem is investigated for nonlinear genetic regulatory networks with stochastic disturbances and time delays, where the nonlinear function describing the feedback regulation is assumed to satisfy the sector condition, the stochastic perturbation is in the form of a scalar Brownian motion, and the time delays exist in both the translation process and the feedback regulation process. The purpose of the addressed filtering problem is to estimate the true concentrations of the mRNA and protein. Specifically, we are interested in designing a linear filter such that, in the presence of time delays, stochastic disturbances as well as sector nonlinearities, the filtering dynamics of state estimation for the stochastic genetic regulatory network is exponentially mean square stable with a prescribed decay rate lower bound beta. By using the linear matrix inequality (LMI) technique, sufficient conditions are first derived for ensuring the desired filtering performance for the gene regulatory model, and the filter gain is then characterized in terms of the solution to an LMI, which can be easily solved by using standard software packages. A simulation example is exploited in order to illustrate the effectiveness of the proposed design procedures

Gain-constrained recursive filtering with stochastic nonlinearities and probabilistic sensor delays

This is the post-print of the Article. The official published version can be accessed from the link below - Copyright @ 2013 IEEE.This paper is concerned with the gain-constrained recursive filtering problem for a class of time-varying nonlinear stochastic systems with probabilistic sensor delays and correlated noises. The stochastic nonlinearities are described by statistical means that cover the multiplicative stochastic disturbances as a special case. The phenomenon of probabilistic sensor delays is modeled by introducing a diagonal matrix composed of Bernoulli distributed random variables taking values of 1 or 0, which means that the sensors may experience randomly occurring delays with individual delay characteristics. The process noise is finite-step autocorrelated. The purpose of the addressed gain-constrained filtering problem is to design a filter such that, for all probabilistic sensor delays, stochastic nonlinearities, gain constraint as well as correlated noises, the cost function concerning the filtering error is minimized at each sampling instant, where the filter gain satisfies a certain equality constraint. A new recursive filtering algorithm is developed that ensures both the local optimality and the unbiasedness of the designed filter at each sampling instant which achieving the pre-specified filter gain constraint. A simulation example is provided to illustrate the effectiveness of the proposed filter design approach.This work was supported in part by the National Natural Science Foundation of China by Grants 61273156, 61028008, 60825303, 61104125, and 11271103, National 973 Project by Grant 2009CB320600, the Fok Ying Tung Education Fund by Grant 111064, the Special Fund for the Author of National Excellent Doctoral Dissertation of China by Grant 2007B4, the State Key Laboratory of Integrated Automation for the Process Industry (Northeastern University) of China, the Engineering and Physical Sciences Research Council (EPSRC) of the U.K. by Grant GR/S27658/01, the Royal Society of the U.K., and the Alexander von Humboldt Foundation of Germany

Robust filtering for stochastic genetic regulatory networks with time-varying delay

This is the post print version of the article. The official published version can be obtained from the link - Copyright 2009 Elsevier LtdThis paper addresses the robust filtering problem for a class of linear genetic regulatory networks (GRNs) with stochastic disturbances, parameter uncertainties and time delays. The parameter uncertainties are assumed to reside in a polytopic region, the stochastic disturbance is state-dependent described by a scalar Brownian motion, and the time-varying delays enter into both the translation process and the feedback regulation process. We aim to estimate the true concentrations of mRNA and protein by designing a linear filter such that, for all admissible time delays, stochastic disturbances as well as polytopic uncertainties, the augmented state estimation dynamics is exponentially mean square stable with an expected decay rate. A delay-dependent linear matrix inequality (LMI) approach is first developed to derive sufficient conditions that guarantee the exponential stability of the augmented dynamics, and then the filter gains are parameterized in terms of the solution to a set of LMIs. Note that LMIs can be easily solved by using standard software packages. A simulation example is exploited in order to illustrate the effectiveness of the proposed design procedures.This work was supported in part by the Biotechnology and Biological Sciences Research Council (BBSRC) of the U.K. under Grants BB/C506264/1 and 100/EGM17735, an International Joint Project sponsored by the Royal Society of the U.K., the Research Grants Council of Hong Kong under Grant HKU 7031/06P, the National Natural Science Foundation of China under Grant 60804028, and the Alexander von Humboldt Foundation of Germany

Network estimation in State Space Model with L1-regularization constraint

Biological networks have arisen as an attractive paradigm of genomic science ever since the introduction of large scale genomic technologies which carried the promise of elucidating the relationship in functional genomics. Microarray technologies coupled with appropriate mathematical or statistical models have made it possible to identify dynamic regulatory networks or to measure time course of the expression level of many genes simultaneously. However one of the few limitations fall on the high-dimensional nature of such data coupled with the fact that these gene expression data are known to include some hidden process. In that regards, we are concerned with deriving a method for inferring a sparse dynamic network in a high dimensional data setting. We assume that the observations are noisy measurements of gene expression in the form of mRNAs, whose dynamics can be described by some unknown or hidden process. We build an input-dependent linear state space model from these hidden states and demonstrate how an incorporated $L_{1}$ regularization constraint in an Expectation-Maximization (EM) algorithm can be used to reverse engineer transcriptional networks from gene expression profiling data. This corresponds to estimating the model interaction parameters. The proposed method is illustrated on time-course microarray data obtained from a well established T-cell data. At the optimum tuning parameters we found genes TRAF5, JUND, CDK4, CASP4, CD69, and C3X1 to have higher number of inwards directed connections and FYB, CCNA2, AKT1 and CASP8 to be genes with higher number of outwards directed connections. We recommend these genes to be object for further investigation. Caspase 4 is also found to activate the expression of JunD which in turn represses the cell cycle regulator CDC2.Comment: arXiv admin note: substantial text overlap with arXiv:1308.359

Extended Kalman filtering with stochastic nonlinearities and multiple missing measurements

Copyright @ 2012 ElsevierIn this paper, the extended Kalman filtering problem is investigated for a class of nonlinear systems with multiple missing measurements over a finite horizon. Both deterministic and stochastic nonlinearities are included in the system model, where the stochastic nonlinearities are described by statistical means that could reflect the multiplicative stochastic disturbances. The phenomenon of measurement missing occurs in a random way and the missing probability for each sensor is governed by an individual random variable satisfying a certain probability distribution over the interval [0,1]. Such a probability distribution is allowed to be any commonly used distribution over the interval [0,1] with known conditional probability. The aim of the addressed filtering problem is to design a filter such that, in the presence of both the stochastic nonlinearities and multiple missing measurements, there exists an upper bound for the filtering error covariance. Subsequently, such an upper bound is minimized by properly designing the filter gain at each sampling instant. It is shown that the desired filter can be obtained in terms of the solutions to two Riccati-like difference equations that are of a form suitable for recursive computation in online applications. An illustrative example is given to demonstrate the effectiveness of the proposed filter design scheme.This work was supported in part by the National 973 Project under Grant 2009CB320600, National Natural Science Foundation of China under Grants 61028008, 61134009 and 60825303, the State Key Laboratory of Integrated Automation for the Process Industry (Northeastern University) of China, the Engineering and Physical Sciences Research Council (EPSRC) of the U.K. under Grant GR/S27658/01, the Royal Society of the U.K., and the Alexander von Humboldt Foundation of Germany

Inference of nonlinear state-space models for sandwich-type lateral flow immunoassay using extended Kalman filtering

Copyright [2011] IEEE. This material is posted here with permission of the IEEE. Such permission of the IEEE does not in any way imply IEEE endorsement of any of Brunel University's products or services. Internal or personal use of this material is permitted. However, permission to reprint/republish this material for advertising or promotional purposes or for creating new collective works for resale or redistribution must be obtained from the IEEE by writing to [email protected]. By choosing to view this document, you agree to all provisions of the copyright laws protecting it.In this paper, a mathematical model for sandwichtype lateral flow immunoassay is developed via short available time series. A nonlinear dynamic stochastic model is considered that consists of the biochemical reaction system equations and the observation equation. After specifying the model structure, we apply the extend Kalman filter (EKF) algorithm for identifying both the states and parameters of the nonlinear state-space model. It is shown that the EKF algorithm can accurately identify the parameters and also predict the system states in the nonlinear dynamic stochastic model through an iterative procedure by using a small number of observations. The identified mathematical model provides a powerful tool for testing the system hypotheses and also inspecting the effects from various design parameters in a both rapid and inexpensive way. Furthermore, by means of the established model, the dynamic changes of the concentration of antigens and antibodies can be predicted, thereby making it possible for us to analyze, optimize and design the properties of lateral flow immunoassay devices.This work was supported in part by the International Science and Technology Cooperation Project of China under Grant 2009DFA32050, Natural Science Foundation of Fujian Province of China under Grants 2009J01280 and 2009J01281

A hybrid EKF and switching PSO algorithm for joint state and parameter estimation of lateral flow immunoassay models

This is the post-print version of the Article. The official published can be accessed from the link below - Copyright @ 2012 IEEEIn this paper, a hybrid extended Kalman filter (EKF) and switching particle swarm optimization (SPSO) algorithm is proposed for jointly estimating both the parameters and states of the lateral flow immunoassay model through available short time-series measurement. Our proposed method generalizes the well-known EKF algorithm by imposing physical constraints on the system states. Note that the state constraints are encountered very often in practice that give rise to considerable difficulties in system analysis and design. The main purpose of this paper is to handle the dynamic modeling problem with state constraints by combining the extended Kalman filtering and constrained optimization algorithms via the maximization probability method. More specifically, a recently developed SPSO algorithm is used to cope with the constrained optimization problem by converting it into an unconstrained optimization one through adding a penalty term to the objective function. The proposed algorithm is then employed to simultaneously identify the parameters and states of a lateral flow immunoassay model. It is shown that the proposed algorithm gives much improved performance over the traditional EKF method.This work was supported in part by the International Science and Technology Cooperation Project of China under Grant 2009DFA32050, Natural Science Foundation of China under Grants 61104041, International Science and Technology Cooperation Project of Fujian Province of China under Grant 2009I0016

Optimal signal processing in small stochastic biochemical networks

We quantify the influence of the topology of a transcriptional regulatory network on its ability to process environmental signals. By posing the problem in terms of information theory, we may do this without specifying the function performed by the network. Specifically, we study the maximum mutual information between the input (chemical) signal and the output (genetic) response attainable by the network in the context of an analytic model of particle number fluctuations. We perform this analysis for all biochemical circuits, including various feedback loops, that can be built out of 3 chemical species, each under the control of one regulator. We find that a generic network, constrained to low molecule numbers and reasonable response times, can transduce more information than a simple binary switch and, in fact, manages to achieve close to the optimal information transmission fidelity. These high-information solutions are robust to tenfold changes in most of the networks' biochemical parameters; moreover they are easier to achieve in networks containing cycles with an odd number of negative regulators (overall negative feedback) due to their decreased molecular noise (a result which we derive analytically). Finally, we demonstrate that a single circuit can support multiple high-information solutions. These findings suggest a potential resolution of the "cross-talk" dilemma as well as the previously unexplained observation that transcription factors which undergo proteolysis are more likely to be auto-repressive.Comment: 41 pages 7 figures, 5 table