Constrained expectation-maximization (EM), dynamic analysis, linear quadratic tracking, and nonlinear constrained expectation-maximation (EM) for the analysis of genetic regulatory networks and signal transduction networks

Despite the immense progress made by molecular biology in cataloging andcharacterizing molecular elements of life and the success in genome sequencing, therehave not been comparable advances in the functional study of complex phenotypes.This is because isolated study of one molecule, or one gene, at a time is not enough byitself to characterize the complex interactions in organism and to explain the functionsthat arise out of these interactions. Mathematical modeling of biological systems isone way to meet the challenge.My research formulates the modeling of gene regulation as a control problem andapplies systems and control theory to the identification, analysis, and optimal controlof genetic regulatory networks. The major contribution of my work includes biologicallyconstrained estimation, dynamical analysis, and optimal control of genetic networks.In addition, parameter estimation of nonlinear models of biological networksis also studied, as a parameter estimation problem of a general nonlinear dynamicalsystem. Results demonstrate the superior predictive power of biologically constrainedstate-space models, and that genetic networks can have differential dynamic propertieswhen subjected to different environmental perturbations. Application of optimalcontrol demonstrates feasibility of regulating gene expression levels. In the difficultproblem of parameter estimation, generalized EM algorithm is deployed, and a set of explicit formula based on extended Kalman filter is derived. Application of themethod to synthetic and real world data shows promising results

Evolutionary-based sparse regression for the experimental identification of duffing oscillator

In this paper, an evolutionary-based sparse regression algorithm is proposed and applied onto experimental data collected from a Duffing oscillator setup and numerical simulation data. Our purpose is to identify the Coulomb friction terms as part of the ordinary differential equation of the system. Correct identification of this nonlinear system using sparse identification is hugely dependent on selecting the correct form of nonlinearity included in the function library. Consequently, in this work, the evolutionary-based sparse identification is replacing the need for user knowledge when constructing the library in sparse identification. Constructing the library based on the data-driven evolutionary approach is an effective way to extend the space of nonlinear functions, allowing for the sparse regression to be applied on an extensive space of functions. The results show that the method provides an effective algorithm for the purpose of unveiling the physical nature of the Duffing oscillator. In addition, the robustness of the identification algorithm is investigated for various levels of noise in simulation. The proposed method has possible applications to other nonlinear dynamic systems in mechatronics, robotics, and electronics

An extended Kalman filtering approach to modeling nonlinear dynamic gene regulatory networks via short gene expression time series

Copyright [2009] 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, the extended Kalman filter (EKF) algorithm is applied to model the gene regulatory network from gene time series data. The gene regulatory network is considered as a nonlinear dynamic stochastic model that consists of the gene measurement equation and the gene regulation equation. After specifying the model structure, we apply the EKF algorithm for identifying both the model parameters and the actual value of gene expression levels. It is shown that the EKF algorithm is an online estimation algorithm that can identify a large number of parameters (including parameters of nonlinear functions) through iterative procedure by using a small number of observations. Four real-world gene expression data sets are employed to demonstrate the effectiveness of the EKF algorithm, and the obtained models are evaluated from the viewpoint of bioinformatics

Quantitative model for inferring dynamic regulation of the tumour suppressor gene p53

Background: The availability of various "omics" datasets creates a prospect of performing the study of genome-wide genetic regulatory networks. However, one of the major challenges of using mathematical models to infer genetic regulation from microarray datasets is the lack of information for protein concentrations and activities. Most of the previous researches were based on an assumption that the mRNA levels of a gene are consistent with its protein activities, though it is not always the case. Therefore, a more sophisticated modelling framework together with the corresponding inference methods is needed to accurately estimate genetic regulation from "omics" datasets. Results: This work developed a novel approach, which is based on a nonlinear mathematical model, to infer genetic regulation from microarray gene expression data. By using the p53 network as a test system, we used the nonlinear model to estimate the activities of transcription factor (TF) p53 from the expression levels of its target genes, and to identify the activation/inhibition status of p53 to its target genes. The predicted top 317 putative p53 target genes were supported by DNA sequence analysis. A comparison between our prediction and the other published predictions of p53 targets suggests that most of putative p53 targets may share a common depleted or enriched sequence signal on their upstream non-coding region. Conclusions: The proposed quantitative model can not only be used to infer the regulatory relationship between TF and its down-stream genes, but also be applied to estimate the protein activities of TF from the expression levels of its target genes

Nonlinear system identification and control using state transition algorithm

By transforming identification and control for nonlinear system into optimization problems, a novel optimization method named state transition algorithm (STA) is introduced to solve the problems. In the proposed STA, a solution to a optimization problem is considered as a state, and the updating of a solution equates to a state transition, which makes it easy to understand and convenient to implement. First, the STA is applied to identify the optimal parameters of the estimated system with previously known structure. With the accurate estimated model, an off-line PID controller is then designed optimally by using the STA as well. Experimental results have demonstrated the validity of the methodology, and comparisons to STA with other optimization algorithms have testified that STA is a promising alternative method for system identification and control due to its stronger search ability, faster convergence rate and more stable performance.Comment: 20 pages, 18 figure

Robust control of room temperature and relative humidity using advanced nonlinear inverse dynamics and evolutionary optimisation

A robust controller is developed, using advanced nonlinear inverse dynamics (NID) controller design and genetic algorithm optimisation, for room temperature control. The performance is evaluated through application to a single zone dynamic building model. The proposed controller produces superior performance when compared to the NID controller optimised with a simple optimisation algorithm, and classical PID control commonly used in the buildings industry. An improved level of thermal comfort is achieved, due to fast and accurate tracking of the setpoints, and energy consumption is shown to be reduced, which in turn means carbon emissions are reduced

GA-tuning of nonlinear observers for sensorless control of automotive power steering IPMSMs

The paper considers two observer-based rotor position estimation schemes for sensorless control of interior permanent magnet synchronous motors (IPMSMs) for use in future automotive power steering systems. Specifically, emphasis is given to techniques based on feedback-linearisation followed by classical Luenberger observer design, and direct design of non-linear observers. Genetic algorithms (GAs), using the principles of evolution, natural selection and genetic mutation, are introduced to address difficulties in selecting correction gains for the observers, since no analytical tuning mechanisms yet exist. Experimental measurements from an automotive power steering test-facility are included, to demonstrate the enhanced performance attributes offered by tuning the proposed observer schemes, online, in this manner

Constrained Nonlinear Model Predictive Control of an MMA Polymerization Process via Evolutionary Optimization

In this work, a nonlinear model predictive controller is developed for a batch polymerization process. The physical model of the process is parameterized along a desired trajectory resulting in a trajectory linearized piecewise model (a multiple linear model bank) and the parameters are identified for an experimental polymerization reactor. Then, a multiple model adaptive predictive controller is designed for thermal trajectory tracking of the MMA polymerization. The input control signal to the process is constrained by the maximum thermal power provided by the heaters. The constrained optimization in the model predictive controller is solved via genetic algorithms to minimize a DMC cost function in each sampling interval.Comment: 12 pages, 9 figures, 28 reference