Systems approach to developmental biology - designs for robust patterning
Patterning is an important step in animal development that generates spatially non-uniform gene expression patterns or spatially heterogeneous cellular responses. Patterning is realised by the generation and reading of positional information provided by spatial gradients of morphogens, diffusive chemicals in the extracellular environment. To achieve normal development, accurate patterning that is robust against noise is necessary. Here the authors describe how morphogen gradient formation and gradient interpretation processes are designed to achieve highly reproducible patterning. Furthermore, recent advancements in measur...
Source: IET Systems Biology - April 1, 2013 Category: Biology Source Type: research
Developing an in silico model of the modulation of base excision repair using methoxyamine for more targeted cancer therapeutics
In this study, the authors have analysed the inhibitory effect of MX on the BER pathway kinetics using a computational model of the repair pathway. The inhibitory effect of MX depends on the BER efficiency. The authors have generated variable efficiency groups using different sets of protein concentrations generated by Latin hypercube sampling, and they have clustered simulation results into high, medium and low efficiency repair groups. From analysis of the inhibitory effect of MX on each of the three groups, it is found that the inhibition is most effective for high efficiency BER, and least effective for low efficiency ...
Source: IET Systems Biology - April 1, 2013 Category: Biology Source Type: research
Genetic programming-based approach to elucidate biochemical interaction networks from data
In this study, the authors propose a genetic programming-based causality detection (GPCD) methodology which blends evolutionary computation-based procedures along with parameter estimation methods to derive a mathematical model of the system. Application of the GPCD methodology on five data sets that contained the different challenges mentioned above indicated that GPCD performs better than the other methods in uncovering the exact structure with less false positives. On a glycolysis data set, GPCD was able to fill the 'interaction gaps' which were missed by other methods. (Source: IET Systems Biology)
Source: IET Systems Biology - February 1, 2013 Category: Biology Source Type: research
Synthetic approaches to study transcriptional networks and noise in mammalian systems
Synthetic biology aims to build new functional organisms and to rationally re-design existing ones by applying the engineering principle of modularity. Apart from building new life forms to perform technical applications, the approach of synthetic biology is useful to dissect complex biological phenomena into simple and easy to understand synthetic modules. Synthetic gene networks have been successfully implemented in prokaryotes and lower eukaryotes, with recent approaches moving ahead towards the mammalian environment. However, synthetic circuits in higher eukaryotes present a more challenging scenario, since its reliabi...
Source: IET Systems Biology - February 1, 2013 Category: Biology Source Type: research
Architecture-dependent robustness in a class of multiple positive feedback loops
In this study, the authors investigate multiple positive feedback loops across three classes: one-loop class, two-loop class and three-loop class, where each class is composed of double positive feedback loop (DPFL) or double negative feedback loop (DNFL) or both. Through large-scale sampling and robustness analysis, the authors find that for a given class, the homogeneous DPFL circuit (i.e. the coupled circuit that is composed of only DPFLs) is more robust than all the other circuits in generating bistable behaviour. In addition, stochastic simulation shows that the low stable state is more robust than the high stable sta...
Source: IET Systems Biology - February 1, 2013 Category: Biology Source Type: research
Computing enclosures for uncertain biochemical systems
In this study, the authors present a novel method that provides enclosures for state trajectories of a non-linear dynamical system with uncertainties in initial conditions and parameter values. It is based on solving positivity conditions by means of semi-definite programmes and sum of squares decompositions. The method accounts for the indeterminacy of kinetic parameters, measurement uncertainties and fluctuations in the reaction rates because of extrinsic noise. This is particularly useful in the field of systems biology when one seeks to determine model behaviour quantitatively or, if this is not possible, semi-quantita...
Source: IET Systems Biology - December 1, 2012 Category: Biology Source Type: research
Design of biomolecular network modifications to achieve adaptation
A biomolecular network is called adaptive if its output returns to the original value after a transient response even under a persisting stimulus. The conditions for adaptation have been investigated thoroughly with systems theory approaches in the literature and it is easy to check whether they are satisfied in the linear approximation. In contrast, it is in general not easy to modify a non-adaptive network model such that it gains adaptive behaviour, especially for medium- and large-scale networks. The authors present a systematic approach based on the notion of kinetic perturbations to construct adaptive biomolecular ne...
Source: IET Systems Biology - December 1, 2012 Category: Biology Source Type: research
Symbolic approach to verification and control of deterministic/probabilistic Boolean networks
In this study, for a BN, the verification/control problems are discussed. First, a probabilistic model including both synchronous and asynchronous Boolean dynamics is derived. This model can be generalised as a probabilistic BN. Next, a solution method of the verification/control problems is proposed, based on a probabilistic model checker PRISM. Finally, the PRISM-based method is applied to an apoptosis network and a WNT5A network. The proposed approach provides us an easy and convenient tool for analysis and control of biological networks. (Source: IET Systems Biology)
Source: IET Systems Biology - December 1, 2012 Category: Biology Source Type: research
Model of the synthesis of trisporic acid in mucorales showing bistability
An important substance in the signalling between individuals of Mucor-like fungi is trisporic acid (TA). This compound, together with some of its precursors, serves as a pheromone in mating between (+)- and (-)-mating types. Moreover, intermediates of the TA pathway are exchanged between the two mating partners. Based on differential equations, mathematical models of the synthesis pathways of TA in the two mating types of an idealised Mucor-fungus are here presented. These models include the positive feedback of TA on its own synthesis. The authors compare three sub-models in view of bistability, robustness and the reversi...
Source: IET Systems Biology - December 1, 2012 Category: Biology Source Type: research
Computing enclosures for uncertain biochemical systems
In this study, the authors present a novel method that provides enclosures for state trajectories of a non-linear dynamical system with uncertainties in initial conditions and parameter values. It is based on solving positivity conditions by means of semidefinite programmes and sum of squares decompositions. The method accounts for the indeterminacy of kinetic parameters, measurement uncertainties and fluctuations in the reaction rates because of extrinsic noise. This is particularly useful in the field of systems biology when one seeks to determine model behaviour quantitatively or, if this is not possible, semiquantitati...
Source: IET Systems Biology - December 1, 2012 Category: Biology Source Type: research
Design of biomolecular network modifications to achieve adaptation
A biomolecular network is called adaptive if its output returns to the original value after a transient response even under a persisting stimulus. The conditions for adaptation have been investigated thoroughly with systems theory approaches in the literature and it is easy to check whether they are satisfied in the linear approximation. In contrast, it is in general not easy to modify a non-adaptive network model such that it gains adaptive behaviour, especially for medium- and large-scale networks. The authors present a systematic approach based on the notion of kinetic perturbations to construct adaptive biomolecular ne...
Source: IET Systems Biology - December 1, 2012 Category: Biology Source Type: research
Symbolic approach to verification and control of deterministic/probabilistic Boolean networks
In this study, for a BN, the verification/control problems are discussed. First, a probabilistic model including both synchronous and asynchronous Boolean dynamics is derived. This model can be generalised as a probabilistic BN. Next, a solution method of the verification/control problems is proposed, based on a probabilistic model checker PRISM. Finally, the PRISM-based method is applied to an apoptosis network and a WNT5A network. The proposed approach provides us an easy and convenient tool for analysis and control of biological networks. (Source: IET Systems Biology)
Source: IET Systems Biology - December 1, 2012 Category: Biology Source Type: research
Model of the synthesis of trisporic acid in mucorales showing bistability
An important substance in the signalling between individuals of Mucor-like fungi is trisporic acid (TA). This compound, together with some of its precursors, serves as a pheromone in mating between (+)- and (2)-mating types. Moreover, intermediates of the TA pathway are exchanged between the two mating partners. Based on differential equations, mathematical models of the synthesis pathways of TA in the two mating types of an idealised Mucor-fungus are here presented. These models include the positive feedback of TA on its own synthesis. The authors compare three sub-models in view of bistability, robustness and the reversi...
Source: IET Systems Biology - December 1, 2012 Category: Biology Source Type: research
