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Mesoscopic statistical properties of multistep enzyme-mediated reactionsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, the authors address this problem by solving the chemical master equations for various enzymatic reactions. A perturbation theory analogous to that used in quantum mechanics allows the determination of the first (langnrang) and the second (sigma2) cumulants of the distribution of created product molecules as a function of the substrate concentration and the kinetic rates of the intermediate processes. The mean product flux V = dlangnrang / dt (or dasiadosedasiaresponsedasia curve) and the Fano factor F = sigma2/langnrang are both realistically measurable quantities, and whereas the mean flux can often appear ...
Source: IET Systems Biology - August 31, 2009 Category: Biology Source Type: journals

Identification of gene interactions in fungal-plant symbiosis through discrete dynamical system modellingEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Fungal-plant root associations involve nutrient exchanges, between the partners and the soil, particularly phosphate, that benefit both organisms. Discrete dynamical system (DDS) models are reconstructed to capture gene regulation in the arbuscular mycorrhizae Glomus versiforme-Medicago trunculata root symbiosis. Previously published time-course gene expression data derived from various days post-inoculation were clustered to identify genes co-regulated in mycorrhizal roots. Uncolonised roots grown with high phosphate provide a key nutritional control condition. First-order linear DDS models were created using a data-drive...
Source: IET Systems Biology - August 31, 2009 Category: Biology Source Type: journals

Scalable learning of large networksEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cellular networks inferred from condition-specific microarray data can capture the functional rewiring of cells in response to different environmental conditions. Unfortunately, many algorithms for inferring cellular networks do not scale to whole-genome data with thousands of variables. We propose a novel approach for scalable learning of large networks: cluster and infer networks (CIN). CIN learns network structures in two steps: (a) partition variables into smaller clusters, and (b) learn networks per cluster. We optionally revisit the cluster assignment of variables with poor neighbourhoods. Results on networks with kn...
Source: IET Systems Biology - August 31, 2009 Category: Biology Source Type: journals

Interampatteness - a generic property of biochemical networksEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Analysis of gene expression data sets reveals that the variation in expression is concentrated to significantly fewer dasiacharacteristic modesdasia or dasiaeigengenesdasia than the number of both recorded assays and measured genes. Previous works have stressed the importance of these characteristic modes, but neglected the equally important weak modes. Herein a generic system property dasia interampatteness dasia is defined that explains the previous feature, and assigns equal weight to the characteristic and weak modes. An interampatte network is characterised by strong INTERactions enabling simultaneous AMPlification an...
Source: IET Systems Biology - August 31, 2009 Category: Biology Source Type: journals

Quantifying evolvability in small biological networksEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The authors introduce a quantitative measure of the capacity of a small biological network to evolve. The measure is applied to a stochastic description of the experimental setup of Guet et al. (Science 2002, 296, pp. 1466), treating chemical inducers as functional inputs to biochemical networks and the expression of a reporter gene as the functional output. The authors take an information-theoretic approach, allowing the system to set parameters that optimise signal processing ability, thus enumerating each network's highest-fidelity functions. All networks studied are highly evolvable by the measure, meaning that change ...
Source: IET Systems Biology - August 31, 2009 Category: Biology Source Type: journals

Evolution of gene auto-regulation in the presence of noiseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Auto-regulatory negative feedback loops, where the protein expressed from a gene inhibits its own expression are common gene network motifs within cells. We investigate when will introducing a negative feedback mechanism be beneficial in terms of increasing a fitness function that is given by the probability of maintaining protein numbers above a critical threshold. Our results show the existence of a trade-off as introducing feedback decreases the average number of protein molecules driving this number closer to the critical threshold (which decreases fitness) but also reduces stochastic fluctuations around the mean (whic...
Source: IET Systems Biology - August 31, 2009 Category: Biology Source Type: journals

Crosstalk between p53 and nuclear factor-κB systems: pro- and anti-apoptotic functions of NF-κBEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Nuclear factors p53 and NF-kappaB control many physiological processes including cell cycle arrest, DNA repair, apoptosis, death, innate and adaptive immune responses, and inflammation. There are numerous pathways linking these systems and there is a bulk of evidence for cooperation as well as for antagonisms between p53 and NF-kappaB. In this theoretical study, the authors use earlier models of p53 and NF-kappaB systems and construct a crosstalk model of p53-NF-kappaB network in order to explore the consequences of the two-way coupling, in which NF-kappaB upregulates the transcription of p53, whereas in turn p53 attenuate...
Source: IET Systems Biology - August 31, 2009 Category: Biology Source Type: journals

Exploring mechanisms of oscillations in p53 and nuclear factor-κb systemsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
A number of regulatory networks have the potential to generate sustained oscillations of irregular amplitude, but well conserved period. Single-cell experiments revealed that in p53 and nuclear factor (NF)-kappaB systems the oscillation period is homogenous in cell populations, insensitive to the strength of the stimulation, and is not influenced by the overexpression of p53 or NF-kappaB transcription factors. We propose a novel computational method of validation of molecular pathways models, based on the analysis of sensitivity of the oscillation period to the particular gene(s) copy number and the level of stimulation. U...
Source: IET Systems Biology - August 31, 2009 Category: Biology Source Type: journals

Sensitivity analysis predicts that the ERK-pMEK interaction regulates ERKEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Following phosphorylation, nuclear translocation of the mitogen-activated protein kinases (MAPKs), ERK1 and ERK2, is critical for both gene expression and DNA replication induced by growth factors. ERK nuclear translocation has therefore been studied extensively, but many details remain unresolved, including whether or not ERK dimerisation is required for translocation. Here, we simulate ERK nuclear translocation with a compartmental computational model that includes systematic sensitivity analysis. The governing ordinary differential equations are solved with the backward differentiation formula and decoupled direct metho...
Source: IET Systems Biology - August 31, 2009 Category: Biology Source Type: journals

Integrating BioPAX pathway knowledge with SBML modelsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Online databases store thousands of molecular interactions and pathways, and numerous modelling software tools provide users with an interface to create and simulate mathematical models of such interactions. However, the two most widespread used standards for storing pathway data (biological pathway exchange; BioPAX) and for exchanging mathematical models of pathways (systems biology markup language; SBML) are structurally and semantically different. Conversion between formats (making data present in one format available in another format) based on simple one-to-one mappings may lead to loss or distortion of data, is diffi...
Source: IET Systems Biology - August 31, 2009 Category: Biology Source Type: journals

Quantitative statistical description of integrin clusters in adherent cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Regulation of protein-protein interactions because of their spatial organisation in cells often shapes cell signalling responses to external stimuli, yet most current cell signalling models do not include spatial segregation of proteins beyond coarse control volumes like the cytosol or nucleus. A significant hindrance to spatial modelling of cell signalling is a lack of data describing the spatial organisation of proteins in cells. One signalling system in which spatial organisation is critical is integrin signalling, where protein interactions are restricted to small, micron-sized protein complexes that form on clusters o...
Source: IET Systems Biology - August 31, 2009 Category: Biology Source Type: journals

Simple model of the transduction of cell-penetrating peptidesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cell-penetrating peptides (CPPs) such as HIV's trans-activating transcriptional activator (TAT) and polyarginine rapidly pass through the plasma membranes of mammalian cells by an unknown mechanism called transduction. They may be medically useful when fused to well-chosen chains of fewer than about 35 amino acids. The author offers a simple model of transduction in which phosphatidylserines and CPPs effectively form two plates of a capacitor with a voltage sufficient to cause the formation of transient pores (electroporation). The model is consistent with experimental data on the transduction of oligoarginine into mouse C...
Source: IET Systems Biology - August 31, 2009 Category: Biology Source Type: journals

Editorial: Selected papers from the Second q-bio Conference on Cellular Information ProcessingEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This special issue consists of 12 original papers that elaborate on work presented at The Second q-bio Conference on Cellular Information Processing, which was held on the campus of St. John¿s College in Santa Fe, New Mexico, USA, 6-9 August 2008. (Source: IET Systems Biology)
Source: IET Systems Biology - August 31, 2009 Category: Biology Source Type: journals

Robust control of uncertain context-sensitive probabilistic Boolean networksEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Uncertainty is an intrinsic phenomenon in control of gene regulatory networks (GRNs). The presence of uncertainty is related to impreciseness of GRN models due to: (1) Errors caused by imperfection of measurement devices and (2) Models¿ inability to fully capture a complex structure of the GRN. Consequently, there is a discrepancy between actual behaviour of the GRN and what is predicted by its mathematical model. This can result in false control signals, which can drive a cell to an undesirable state. To address the problem of control under uncertainties, a risk-sensitive control paradigm is proposed. Robustness is accom...
Source: IET Systems Biology - June 30, 2009 Category: Biology Source Type: journals

Detection of local community structures in complex dynamic networks with random walksEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study the authors propose a novel approach to identify local communities based on iterative agglomeration and local optimisation. The proposed solution has two significant improvements: (i) in each iteration, agglomeration strengthens the local community measure by selecting the best possible set of vertices, and (ii) the proposed vertex and community rank criterion are suitable for the dynamic networks where the interactions among vertices may change over time. In order to evaluate the proposed algorithm, extensive experiments and benchmarking on computer generated networks as well as real-world social and biologi...
Source: IET Systems Biology - June 30, 2009 Category: Biology Source Type: journals

Analysis of an apoptotic core model focused on experimental design using artificial dataEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The activation of caspases is a central mechanism in apoptosis. To gain further insights into complex processes like this, mathematical modelling using ordinary differential equations (ODEs) can be a very powerful research tool. Unfortunately, the lack of measurement data is a common problem in building such kinetic models, because it practically constrains the identifiability of the model parameters. An existing mathematical model of caspase activation during apoptosis was used in order to design future experimental setups that will help to maximise the obtained information. For this purpose, artificial measurement data a...
Source: IET Systems Biology - June 30, 2009 Category: Biology Source Type: journals

Multi-element probabilistic collocation for sensitivity analysis in cellular signalling networksEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The multi-element probabilistic collocation method (ME-PCM) as a tool for sensitivity analysis of differential equation models as applied to cellular signalling networks is formulated. This method utilises a simple, efficient sampling algorithm to quantify local sensitivities throughout the parameter space. The application of the ME-PCM to a previously published ordinary differential equation model of the apoptosis signalling network is presented. The authors verify agreement with the previously identified regions of sensitivity and then go on to analyse this region in greater detail with the ME-PCM. The authors demonstrat...
Source: IET Systems Biology - June 30, 2009 Category: Biology Source Type: journals

Biological mechanisms revealed by a mathematical model for p53-Mdm2 core regulationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, a new mathematical model is built to characterise the p53-Mdm2 interaction based on the recent biological findings, as well as a few reasonable hypotheses and approximations. The dynamics of ATM (Ataxia Telangiectasia Mutated) is introduced to the model so as to connect DNA damage signal with the core regulation. The simulation results are in good accord with the experimental observations in the literature. More importantly, through bifurcation analysis on the model, a new threshold mechanism is predicted with respect to the dose of ionising radiation (IR). Furthermore, a novel frequency shifting phenomenon ...
Source: IET Systems Biology - June 30, 2009 Category: Biology Source Type: journals

Genome-wide system analysis reveals stable yet flexible network dynamics in yeastEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recently, important insights into static network topology for biological systems have been obtained, but still global dynamical network properties determining stability and system responsiveness have not been accessible for analysis. Herein, we explore a genome-wide gene-to-gene regulatory network based on expression data from the cell cycle in Saccharomyces cerevisae (budding yeast). We recover static properties like hubs (genes having several out-going connections), network motifs and modules, which have previously been derived from multiple data sources such as whole-genome expression measurements, literature mining, pr...
Source: IET Systems Biology - June 30, 2009 Category: Biology Source Type: journals

Discrete dynamical system modelling for gene regulatory networks of 5-hydroxymethylfurfural tolerance for ethanologenic yeastEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Composed of linear difference equations, a discrete dynamical system (DDS) model was designed to reconstruct transcriptional regulations in gene regulatory networks (GRNs) for ethanologenic yeast Saccharomyces cerevisiae in response to 5-hydroxymethylfurfural (HMF), a bioethanol conversion inhibitor. The modelling aims at identification of a system of linear difference equations to represent temporal interactions among significantly expressed genes. Power stability is imposed on a system model under the normal condition in the absence of the inhibitor. Non-uniform sampling, typical in a time-course experimental design, is ...
Source: IET Systems Biology - May 21, 2009 Category: Biology Source Type: journals

Inference of Boolean networks under constraint on bidirectional gene relationshipsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The coefficient of determination (CoD) has been used to infer Boolean networks (BNs) from steady-state data, in particular, to estimate the constituent BNs for a probabilistic BN. The advantage of the CoD method over design methods that emphasise graph topology or attractor structure is that the CoD produces a network based on strong predictive relationships between target genes and their predictor (parent) genes. The disadvantage is that spurious attractor cycles appear in the inferred network, so that there is poor inference relative to the attractor structure, that is, relative to the steady-state behaviour of the netwo...
Source: IET Systems Biology - May 21, 2009 Category: Biology Source Type: journals

Chemotherapy may be delivered based on an integrated view of tumour dynamicsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The aim here was to explore the potential of pharmacokinetic (PK)/pharmacodynamic (PD) and physiopathological parameters in explaining the primary effects of an anti-cancer treatment that targets cells in a specific cell cycle phase. The authors applied a theoretical multi-scale disease model of tumour growth that integrates cancer processes at the cellular and tissue scales. The mathematical model at the cell level relies on a dynamic description of cell cycle regulation while the model at the tissue level is based on fluid mechanics considerations. Simulations show that the number of target cells oscillates as the tumour...
Source: IET Systems Biology - May 21, 2009 Category: Biology Source Type: journals

Steady-state and dynamic flux balance analysis of ethanol production by Saccharomyces cerevisiaeEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Steady-state and dynamic flux balance analysis (DFBA) was used to investigate the effects of metabolic model complexity and parameters on ethanol production predictions for wild-type and engineered Saccharomyces cerevisiae. Three metabolic network models ranging from a single compartment representation of metabolism to a genome-scale reconstruction with seven compartments and detailed charge balancing were studied. Steady-state analysis showed that the models generated similar wild-type predictions for the biomass and ethanol yields, but for ten engineered strains the seven compartment model produced smaller ethanol yield ...
Source: IET Systems Biology - May 21, 2009 Category: Biology Source Type: journals

Genetic network identification using convex programmingEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Gene regulatory networks capture interactions between genes and other cell substances, resulting in various models for the fundamental biological process of transcription and translation. The expression levels of the genes are typically measured as mRNA concentration in micro-array experiments. In a so-called genetic perturbation experiment, small perturbations are applied to equilibrium states and the resulting changes in expression activity are measured. One of the most important problems in systems biology is to use these data to identify the interaction pattern between genes in a regulatory network, especially in a lar...
Source: IET Systems Biology - May 21, 2009 Category: Biology Source Type: journals

Modelling and analysis of the sugar cataract development process using stochastic hybrid systemsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Modelling and analysis of biochemical systems such as sugar cataract development (SCD) are critical because they can provide new insights into systems, which cannot be easily tested with experiments; however, they are challenging problems due to the highly coupled chemical reactions that are involved. The authors present a stochastic hybrid system (SHS) framework for modelling biochemical systems and demonstrate the approach for the SCD process. A novel feature of the framework is that it allows modelling the effect of drug treatment on the system dynamics. The authors validate the three sugar cataract models by comparing ...
Source: IET Systems Biology - May 21, 2009 Category: Biology Source Type: journals

SysBioMed report: Advancing systems biology for medical applicationsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The following report selects and summarises some of the conclusions and recommendations generated throughout a series of workshops and discussions that have lead to the publication of the Science Policy Briefing (SPB) Nr. 35, published by the European Science Foundation. (Large parts of the present text are directly based on the ESF SPB. Detailed recommendations with regard to specific application areas are not given here but can be found in the SPB. Issues related to mathematical modelling, including training and the need for an infrastructure supporting modelling are discussed in greater detail in the present text.) The ...
Source: IET Systems Biology - May 21, 2009 Category: Biology Source Type: journals

Deconstructing the core dynamics from a complex time-lagged regulatory biological circuitEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Complex regulatory dynamics is ubiquitous in molecular networks composed of genes and proteins. Recent progress in computational biology and its application to molecular data generate a growing number of complex networks. Yet, it has been difficult to understand the governing principles of these networks beyond graphical analysis or extensive numerical simulations. Here the authors exploit several simplifying biological circumstances which thereby enable to directly detect the underlying dynamical regularities driving periodic oscillations in a dynamical nonlinear computational model of a protein¿protein network. System a...
Source: IET Systems Biology - March 28, 2009 Category: Biology Source Type: journals

Synchronisation mechanisms of circadian rhythms in the suprachiasmatic nucleusEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus is considered as the master circadian pacemaker. Each cell in the SCN contains an autonomous molecular clock, and the SCN is composed of multiple single-cell circadian oscillators. The fundamental question is how the individual cellular oscillators, expressing a wide range of periods, interact and assemble to create an integrated pacemaker that can govern behavioural and physiological rhythmicity and be reset by environmental light. The key is that the heterogeneous network formed by the cellular clocks within the SCN must synchronise to maintain timekeeping...
Source: IET Systems Biology - March 28, 2009 Category: Biology Source Type: journals

Optimal control policy for probabilistic Boolean networks with hard constraintsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
It is well known that the control/intervention of some genes in a genetic regulatory network is useful for avoiding undesirable states associated with some diseases like cancer. For this purpose, both optimal finitehorizon control and infinite-horizon control policies have been proposed. Boolean networks (BNs) and its extension probabilistic Boolean networks (PBNs) as useful and effective tools for modelling gene regulatory systems have received much attention in the biophysics community. The control problem for these models has been studied widely. The optimal control problem in a PBN can be formulated as a probabilistic ...
Source: IET Systems Biology - March 28, 2009 Category: Biology Source Type: journals

BioXyce: an engineering platform for the study of cellular systemsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Researchers use constructs from the field of electrical engineering for the modelling and analysis of biological systems, but few exploit parallels between electrical and biological circuits for simulation purposes. The authors discuss the development of BioXyce, a circuit-based biological simulation platform that uses XyceTM, a large-scale electrical circuit simulator, as its simulation engine. BioXyce is capable of simulating whole-cell and multicellular systems. Simulation results for the central metabolism in Escherichia coli K12 and cellular differentiation in Drosophila sp. are presented. (Source: IET Systems Biology)
Source: IET Systems Biology - March 28, 2009 Category: Biology Source Type: journals

Role of inhibitory proteins as modulators of oscillations in NFγkB signallingEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The authors discuss the role of the Raf kinase inhibitory protein (RKIP) as a modulator of oscillations in NFγkB signalling. A mathematical model of the NFγkB signalling pathway was derived and the Lyapunov¿Andronov theory was used to analyse dynamical properties of the system. The analytical results were complemented by predictive numerical simulations. Our results suggest that the nature of oscillations, emerging under sustained stimulation of the system, depends on the interplay between the IkB kinase (IKK) stimulation and the inhibitory action of RKIP. The authors found a mathematical relation that def...
Source: IET Systems Biology - March 28, 2009 Category: Biology Source Type: journals

Moment-closure approximations for mass-action modelsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Although stochastic population models have proved to be a powerful tool in the study of process generating mechanisms across a wide range of disciplines, all too often the associated mathematical development involves nonlinear mathematics, which immediately raises difficult and challenging analytic problems that need to be solved if useful progress is to be made. One approximation that is often employed to estimate the moments of a stochastic process is moment closure. This approximation essentially truncates the moment equations of the stochastic process. A general expression for the marginal- and joint-moment equations f...
Source: IET Systems Biology - January 28, 2009 Category: Biology Source Type: journals

Proper lumping in systems biology modelsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
An algorithm for automatic order reduction of models defined by large systems of differential equations is presented. The algorithm was developed with systems biology models in mind and the motivation behind it is to develop mechanistic pharmacokinetic/pharmacodynamic models from already available systems biology models. The approach used for model reduction is proper lumping of the system¿s states and is based on a search through the possible combinations of lumps. To avoid combinatorial explosion, a heuristic, greedy search strategy is employed and comparison with the full exhaustive search provides evidence that it per...
Source: IET Systems Biology - January 28, 2009 Category: Biology Source Type: journals

Mixed-integer nonlinear optimisation approach to coarse-graining biochemical networksEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Quantitative modelling and analysis of biochemical networks is challenging because of the inherent complexities and nonlinearities of the system and the limited availability of parameter values. Even if a mathematical model of the network can be developed, the lack of large-scale good-quality data makes accurate estimation of a large number of parameters impossible. Hence, coarse-grained models (CGMs) consisting of essential biochemical mechanisms are more suitable for computational analysis and for studying important systemic functions. The central question in constructing a CGM is which mechanisms should be deemed ?essen...
Source: IET Systems Biology - January 28, 2009 Category: Biology Source Type: journals

Optimal experimental design with the sigma point methodEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Using mathematical models for a quantitative description of dynamical systems requires the identification of uncertain parameters by minimising the difference between simulation and measurement. Owing to the measurement noise also, the estimated parameters possess an uncertainty expressed by their variances. To obtain highly predictive models, very precise parameters are needed. The optimal experimental design (OED) as a numerical optimisation method is used to reduce the parameter uncertainty by minimising the parameter variances iteratively. A frequently applied method to define a cost function for OED is based on the in...
Source: IET Systems Biology - January 28, 2009 Category: Biology Source Type: journals

Nested uncertainties in biochemical modelsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Dynamic modelling of biochemical reaction networks has to cope with the inherent uncertainty about biological processes, concerning not only data and parameters but also kinetics and structure. These different types of uncertainty are nested within each other: uncertain network structures contain uncertain reaction kinetics, which in turn are governed by uncertain parameters. Here, the authors review some issues arising from such uncertainties and sketch methods, solutions and future directions to deal with them. (Source: IET Systems Biology)
Source: IET Systems Biology - January 28, 2009 Category: Biology Source Type: journals

Genetical systems biology in livestock: application to gonadotrophin releasing hormone and reproductionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Genetical systems biology or systems genetics treats the genome as the central reference point for all omics variations and is an emerging new branch of systems biology. Quantitative genetic principles were developed for high-throughput genomic, transcriptomic and metabolomic data observed in large populations. New statistical genetic models were developed for expression quantitative trait loci (eQTL), namely, marker regression eQTL mapping and marker-expression co-factor mapping. Evaluations of power to detect eQTL showed that sample size requirements are higher for detecting trans-acting genes than cis-acting genes. Powe...
Source: IET Systems Biology - November 21, 2008 Category: Biology Source Type: journals

Computational modelling identifies the impact of subtle anatomical variations between amphibian and mammalian skeletal muscle on spatiotemporal calcium dynamicsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The physical sites of calcium entry and exit in the skeletal muscle cell are distinct and highly organised in space. It was investigated whether the highly structured spatial organisation of sites of Ca2 release, uptake and action in skeletal muscle cells substantially impacts the dynamics of cytosolic Ca2 handling and thereby the physiology of the cell. Hereto, the spatiotemporal dynamics of the free calcium distribution in a fast-twitch (FT) muscle sarcomere was studied using a reaction¿diffusion computational model for two genotypes with known anatomical differences. A computational model of a murine FT muscle sarcomer...
Source: IET Systems Biology - November 21, 2008 Category: Biology Source Type: journals

Control, responses and modularity of cellular regulatory networks: a control analysis perspectiveEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cells adapt to changes in environmental conditions through the concerted action of signalling, gene expression and metabolic subsystems. The authors will discuss a theoretical framework addressing such integrated systems. This 'hierarchical analysis' was first developed as an extension to a metabolic control analysis. It builds on the phenomenon that often the communication between signalling, gene expression and metabolic subsystems is almost exclusively via regulatory interactions and not via mass flow interactions. This allows for the treatment of the said subsystems as 'levels' in a hierarchical view of the organisatio...
Source: IET Systems Biology - November 21, 2008 Category: Biology Source Type: journals

Computational inference of replication and transcription activator regulator activity in herpesvirus from gene expression dataEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
One of the main aims of system biology is to understand the structure and dynamics of genomic systems. A computational approach, facilitated by new technologies for high-throughput quantitative experimental data, is put forward to investigate the regulatory system of dynamic interaction among genes in Kaposi¿s sarcoma-associated herpesvirus network after induction of lytic replication. A reconstruction of transcription factor activity and gene-regulatory kinetics using data from a time-course microarray experiment is proposed. The computational approach uses nonlinear differential equations. In particular, the quantitativ...
Source: IET Systems Biology - November 21, 2008 Category: Biology Source Type: journals

Editorial - Selected papers from the 'Omics: Assembling Systems Biology' WorkshopEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
System-oriented biological research (Systems Biology) is a vibrant field which aims to establish the higher-order principles behind complex multi-cellular processes. This classic theme of the Life Sciences was recently reinforced with a new armamentarium of high-throughput molecular tools. These omics approaches ('omes', greek for 'complete') allow us to now study biological behaviour in unprecedented width and detail. Consequently, Systems Biology is seen to bear the potential for major discoveries in the Life Sciences. (Source: IET Systems Biology)
Source: IET Systems Biology - November 21, 2008 Category: Biology Source Type: journals

Incorporating genome-wide DNA sequence information into a dynamic whole-cell model of Escherichia coli: application to DNA replicationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The advent of thousands of annotated genomes, detailed metabolic reconstructions and databases within the flourishing field of systems biology necessitates the development of functionally complete computer models of whole cells and cellular systems. Such models would realistically describe fundamental properties of living systems such as growth, division and chromosome replication. This will inevitably bridge bioinformatic technologies with ongoing mathematical modelling efforts and would allow for in silico prediction of important dynamic physiological events. To demonstrate a potential for the anticipated merger of bioin...
Source: IET Systems Biology - September 25, 2008 Category: Biology Source Type: journals

Complexity and modularity of intracellular networks: a systematic approach for modelling and simulationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Assembly of quantitative models of large complex networks brings about several challenges. One of them is the combinatorial complexity, where relatively few signalling molecules can combine to form thousands or millions of distinct chemical species. A receptor that has several separate phosphorylation sites can exist in hundreds of different states, many of which must be accounted for individually when simulating the time course of signalling. When assembly of protein complexes is being included, the number of distinct molecular species can easily increase by a few orders of magnitude. Validation, visualisation and underst...
Source: IET Systems Biology - September 25, 2008 Category: Biology Source Type: journals

Virtual cell modelling and simulation software environmentEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The Virtual Cell (VCell; http://vcell.org/) is a problem solving environment, built on a central database, for analysis, modelling and simulation of cell biological processes. VCell integrates a growing range of molecular mechanisms, including reaction kinetics, diffusion, flow, membrane transport, lateral membrane diffusion and electrophysiology, and can associate these with geometries derived from experimental microscope images. It has been developed and deployed as a web-based, distributed, client?server system, with more than a thousand world-wide users. VCell provides a separation of layers (core technologies and abst...
Source: IET Systems Biology - September 25, 2008 Category: Biology Source Type: journals

Domain-oriented reduction of rule-based network modelsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The coupling of membrane-bound receptors to transcriptional regulators and other effector functions is mediated by multi-domain proteins that form complex assemblies. The modularity of protein interactions lends itself to a rule-based description, in which species and reactions are generated by rules that encode the necessary context for an interaction to occur, but also can produce a combinatorial explosion in the number of chemical species that make up the signalling network. The authors have shown previously that exact network reduction can be achieved using hierarchical control relationships between sites/domains on pr...
Source: IET Systems Biology - September 25, 2008 Category: Biology Source Type: journals

Detailed comparison between StochSim and SSAEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Morton-Firth and Bray¿s stochastic simulator (StochSim) and Gillespie¿s stochastic simulation algorithm (SSA) are two important methods for stochastic modelling and simulation of biochemical systems. They have been widely applied to different biological problems. A key question is discussed here: Are these two methods equivalent? These two methods are compared using fundamental probability analysis. The analysis clearly shows that, when the time step in the StochSim is chosen very small, the StochSim can be viewed as a first-order approximation to the SSA. The analysis also explains why the SSA is usually much more effic...
Source: IET Systems Biology - September 25, 2008 Category: Biology Source Type: journals

Transient analysis of stochastic switches and trajectories with applications to gene regulatory networksEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This article also presents two systems-theory based FSP model reduction approaches that are particularly useful in such studies. The benefits of these approaches are illustrated in the analysis of the stochastic switching behaviour of Gardner¿s genetic toggle switch. (Source: IET Systems Biology)
Source: IET Systems Biology - September 25, 2008 Category: Biology Source Type: journals

Serially regulated biological networks fully realise a constrained set of functionsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
It is shown that biological networks with serial regulation (each node regulated by at most one other node) are constrained to direct functionality, in which the sign of the effect of an environmental input on a target species depends only on the direct path from the input to the target, even when there is a feedback loop allowing for multiple interaction pathways. Using a stochastic model for a set of small transcriptional regulatory networks that have been studied experimentally, it is further found that all networks can achieve all functions permitted by this constraint under reasonable settings of biochemical parameter...
Source: IET Systems Biology - September 25, 2008 Category: Biology Source Type: journals

Satisfiability, sequence niches and molecular codes in cellular signallingEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological information processing as implemented by regulatory and signalling networks in living cells requires sufficient specificity of molecular interaction to distinguish signals from one another, but much of regulation and signalling involves somewhat fuzzy and promiscuous recognition of molecular sequences and structures, which can leave systems vulnerable to crosstalk. A simple model of biomolecular interactions that reveals both a sharp onset of crosstalk and a fragmentation of the neutral network of viable solutions is examined as more proteins compete for regions of sequence space, revealing intrinsic limits to r...
Source: IET Systems Biology - September 25, 2008 Category: Biology Source Type: journals

Determinants of bistability in induction of the Escherichia coli lac operonEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The authors have developed a mathematical model of regulation of expression of the Escherichia coli lac operon, and have investigated bistability in its steady-state induction behaviour in the absence of external glucose. Numerical analysis of equations describing regulation by artificial inducers revealed two natural bistability parameters that can be used to control the range of inducer concentrations over which the model exhibits bistability. By tuning these bistability parameters, the authors found a family of biophysically reasonable systems that are consistent with an experimentally determined bistable region for ind...
Source: IET Systems Biology - September 25, 2008 Category: Biology Source Type: journals