11,161 research outputs found
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
Gene regulatory networks: a coarse-grained, equation-free approach to multiscale computation
We present computer-assisted methods for analyzing stochastic models of gene
regulatory networks. The main idea that underlies this equation-free analysis
is the design and execution of appropriately-initialized short bursts of
stochastic simulations; the results of these are processed to estimate
coarse-grained quantities of interest, such as mesoscopic transport
coefficients. In particular, using a simple model of a genetic toggle switch,
we illustrate the computation of an effective free energy and of a
state-dependent effective diffusion coefficient that characterize an
unavailable effective Fokker-Planck equation. Additionally we illustrate the
linking of equation-free techniques with continuation methods for performing a
form of stochastic "bifurcation analysis"; estimation of mean switching times
in the case of a bistable switch is also implemented in this equation-free
context. The accuracy of our methods is tested by direct comparison with
long-time stochastic simulations. This type of equation-free analysis appears
to be a promising approach to computing features of the long-time,
coarse-grained behavior of certain classes of complex stochastic models of gene
regulatory networks, circumventing the need for long Monte Carlo simulations.Comment: 33 pages, submitted to The Journal of Chemical Physic
Parameters identification of unknown delayed genetic regulatory networks by a switching particle swarm optimization algorithm
The official published version can be found at the link below.This paper presents a novel particle swarm optimization (PSO) algorithm based on Markov chains and competitive penalized method. Such an algorithm is developed to solve global optimization problems with applications in identifying unknown parameters of a class of genetic regulatory networks (GRNs). By using an evolutionary factor, a new switching PSO (SPSO) algorithm is first proposed and analyzed, where the velocity updating equation jumps from one mode to another according to a Markov chain, and acceleration coefficients are dependent on mode switching. Furthermore, a leader competitive penalized multi-learning approach (LCPMLA) is introduced to improve the global search ability and refine the convergent solutions. The LCPMLA can automatically choose search strategy using a learning and penalizing mechanism. The presented SPSO algorithm is compared with some well-known PSO algorithms in the experiments. It is shown that the SPSO algorithm has faster local convergence speed, higher accuracy and algorithm reliability, resulting in better balance between the global and local searching of the algorithm, and thus generating good performance. Finally, we utilize the presented SPSO algorithm to identify not only the unknown parameters but also the coupling topology and time-delay of a class of GRNs.This research was partially supported by the National Natural Science Foundation of PR China (Grant No. 60874113), the Research Fund for the Doctoral Program of Higher Education (Grant No. 200802550007), the Key Creative Project of Shanghai Education Community (Grant No. 09ZZ66), the Key Foundation Project of Shanghai (Grant No. 09JC1400700), the Engineering and Physical Sciences Research Council EPSRC of the UK under Grant No. GR/S27658/01, the International Science and Technology Cooperation Project of China under Grant No. 2009DFA32050, an International Joint Project sponsored by the Royal Society of the UK, and the Alexander von Humboldt Foundation of Germany
Estimation of kinetic rates of MAP kinase activation from experimental data
Mathematical model is an important tool in systems biology to study the dynamics of biological systems inside the cell. One of the significant challenges in systems biology is the lack of kinetic rates that should be measured in experiments or estimated from experimental data. This work addresses this issue by using a genetic algorithm to estimate reaction rates related to the phosphorylation and dephosphorylation of MAP kinase (ERK) in the mitogen-activated protein (MAP) kinase pathway from biological measurements. In addition, we discuss the robustness of the mathematical model with regards to the variation of kinetic rates together with external noise due to environmental fluctuations. This has been proposed as an additional criterion to choose the estimate from the candidate parameter sets that are obtained from different implementations of the genetic algorithm
Intrinsic noise profoundly alters the dynamics and steady state of morphogen-controlled bistable genetic switches
During tissue development, patterns of gene expression determine the spatial
arrangement of cell types. In many cases, gradients of secreted signaling
molecules - morphogens - guide this process. The continuous positional
information provided by the gradient is converted into discrete cell types by
the downstream transcriptional network that responds to the morphogen. A
mechanism commonly used to implement a sharp transition between two adjacent
cell fates is the genetic toggle switch, composed of cross-repressing
transcriptional determinants. Previous analyses emphasize the steady state
output of these mechanisms. Here, we explore the dynamics of the toggle switch
and use exact numerical simulations of the kinetic reactions, the Chemical
Langevin Equation, and Minimum Action Path theory to establish a framework for
studying the effect of gene expression noise on patterning time and boundary
position. This provides insight into the time scale, gene expression
trajectories and directionality of stochastic switching events between cell
states. Taking gene expression noise into account predicts that the final
boundary position of a morphogen-induced toggle switch, although robust to
changes in the details of the noise, is distinct from that of the deterministic
system. Moreover, stochastic switching introduces differences in patterning
time along the morphogen gradient that result in a patterning wave propagating
away from the morphogen source. The velocity of this wave is influenced by
noise; the wave sharpens and slows as it advances and may never reach steady
state in a biologically relevant time. This could explain experimentally
observed dynamics of pattern formation. Together the analysis reveals the
importance of dynamical transients for understanding morphogen-driven
transcriptional networks and indicates that gene expression noise can
qualitatively alter developmental patterning
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 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
Data based identification and prediction of nonlinear and complex dynamical systems
We thank Dr. R. Yang (formerly at ASU), Dr. R.-Q. Su (formerly at ASU), and Mr. Zhesi Shen for their contributions to a number of original papers on which this Review is partly based. This work was supported by ARO under Grant No. W911NF-14-1-0504. W.-X. Wang was also supported by NSFC under Grants No. 61573064 and No. 61074116, as well as by the Fundamental Research Funds for the Central Universities, Beijing Nova Programme.Peer reviewedPostprin
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