Multi-scale approach for simulating time-delay biochemical reaction systems
This study presents a multi-scale approach for simulating time-delay biochemical reaction systems when there are wide ranges of molecular numbers. The authors construct a new efficient approach based on partitioning into slow and fast subsets in conjunction with predictor–corrector methods. This multi-scale approach is shown to be much more efficient than existing methods such as the delay stochastic simulation algorithm and the modified next reaction method. Numerical testing on several important problems in systems biology confirms the accuracy and computational efficiency of this approach. (Source: IET Systems Biology)
Source: IET Systems Biology - January 13, 2015 Category: Biology Source Type: research
Evolutionary dynamics of morphological stability in a long-term experiment with Escherichia coli
To investigate the questions in morphological evolution, some biologists seek to carry out evolution experiments owing to the incompleteness and uncontrollability of the fossil record and natural populations. To quantitatively analyse the morphology (cell size) evolution observed from a long-term experiment with Escherichia coli, the authors present three mathematical approximations to the Wright–Fisher model of the morphological evolution. They firstly use a deterministic approximation, which fails to predict evolutionary dynamics of cell size and proves the importance of stochasticity in large populations. Then, th...
Source: IET Systems Biology - January 13, 2015 Category: Biology Source Type: research
Properties of sparse penalties on inferring gene regulatory networks from time-course gene expression data
Genes regulate each other and form a gene regulatory network (GRN) to realise biological functions. Elucidating GRN from experimental data remains a challenging problem in systems biology. Numerous techniques have been developed and sparse linear regression methods become a promising approach to infer accurate GRNs. However, most linear methods are either based on steady-state gene expression data or their statistical properties are not analysed. Here, two sparse penalties, adaptive least absolute shrinkage and selection operator and smoothly clipped absolute deviation, are proposed to infer GRNs from time-course gene expr...
Source: IET Systems Biology - January 13, 2015 Category: Biology Source Type: research
Fundamental limitation of the instantaneous approximation in fold-change detection models
This study establishes a fundamental limitation of such a mechanism, showing that there is a minimal fold-change detection error that cannot be overcome, no matter how large the separation of time scales is. To illustrate this theoretically predicted limitation, the authors discuss two common biomolecular network motifs, an incoherent feedforward loop and a feedback system, as well as a published model of the chemotaxis signalling pathway of Dictyostelium discoideum. (Source: IET Systems Biology)
Source: IET Systems Biology - January 13, 2015 Category: Biology Source Type: research
Ubiquitin chain specific auto-ubiquitination triggers sustained oscillation, bistable switches and excitable firing
Ubiquitin modification of cellular proteins commonly targets them for proteosomal degradation, but can also convey non-proteolytic functions. Over the past years, advances in experimental approaches have helped uncover the extensive involvement of ubiquitination in protein regulation. However, our understanding of the dynamics of the ubiquitination-related networks have lagged behind. A common regulatory theme for many E3 ligases is the ability to self-catalyse their own ubiquitination without involving external E3 ligating enzymes. Here, the authors have explored computational models of both proteolytic and non-proteolyti...
Source: IET Systems Biology - December 9, 2014 Category: Biology Source Type: research
Comparison of adaptation motifs: temporal, stochastic and spatial responses
The cells’ ability to adapt to changes in the external environment is crucial for the survival of many organisms. There are two broad classes of signalling networks that achieve perfect adaptation. Both rely on complementary regulation of the response by an external signal and an inhibitory process. In one class of systems, inhibition comes about from the response itself, closing a negative feedback (NFB) loop. In the other, the inhibition comes directly from the external signal in what is referred to as an incoherent feedforward (IFF) loop. Although both systems show adaptive behaviour to constant changes in the lev...
Source: IET Systems Biology - December 9, 2014 Category: Biology Source Type: research
A technique for determining the signs of sensitivities of steady states in chemical reaction networks
This paper studies the direction of change of steady states to parameter perturbations in chemical reaction networks, and, in particular, to changes in conserved quantities. Theoretical considerations lead to the formulation of a computational procedure that provides a set of possible signs of such sensitivities. The procedure is purely algebraic and combinatorial, only using information on stoichiometry, and is independent of the values of kinetic constants. Three examples of important intracellular signal transduction models are worked out as an illustration. In these examples, the set of signs found is minimal, but ther...
Source: IET Systems Biology - December 9, 2014 Category: Biology Source Type: research
Pushing limits by embracing complexity
In this essay, celebrating the tenth anniversary of this journal, the author describes his journey, from being an engineering student to being a researcher in the biomolecular and biomedical sciences. Along the way, he is going to explain how he learned that handling the complexity of biological systems and cellular processes can provide guidance in situation we all face in our everyday life. In particular, he has in mind the decisions one faces in choosing the topic for a University degree and how to deal with the uncertainty when it comes to career decisions. Looking back at a decade of mathematical modelling in the biol...
Source: IET Systems Biology - December 9, 2014 Category: Biology Source Type: research
Editorial
(Source: IET Systems Biology)
Source: IET Systems Biology - December 9, 2014 Category: Biology Source Type: research
Accounting for randomness in measurement and sampling in studying cancer cell population dynamics
Knowing the expected temporal evolution of the proportion of different cell types in sample tissues gives an indication about the progression of the disease and its possible response to drugs. Such systems have been modelled using Markov processes. We here consider an experimentally realistic scenario in which transition probabilities are estimated from noisy cell population size measurements. Using aggregated data of FACS measurements, we develop MMSE and ML estimators and formulate two problems to find the minimum number of required samples and measurements to guarantee the accuracy of predicted population sizes. Our num...
Source: IET Systems Biology - October 1, 2014 Category: Biology Source Type: research
Dynamic flux balance analysis for synthetic microbial communities
Dynamic flux balance analysis (DFBA) is an extension of classical flux balance analysis that allows the dynamic effects of the extracellular environment on microbial metabolism to be predicted and optimised. Recently this computational framework has been extended to microbial communities for which the individual species are known and genome-scale metabolic reconstructions are available. In this review, the authors provide an overview of the emerging DFBA approach with a focus on two case studies involving the conversion of mixed hexose/pentose sugar mixtures by synthetic microbial co-culture systems. These case studies ill...
Source: IET Systems Biology - October 1, 2014 Category: Biology Source Type: research
Multiscale computational models in physical systems biology of intracellular trafficking
In intracellular trafficking, a definitive understanding of the interplay between protein binding and membrane morphology remains incomplete. The authors describe a computational approach by integrating coarse-grained molecular dynamics (CGMD) simulations with continuum Monte Carlo (CM) simulations of the membrane to study protein-membrane interactions and the ensuing membrane curvature. They relate the curvature field strength discerned from the molecular level to its effect at the cellular length-scale. They perform thermodynamic integration on the CM model to describe the free energy landscape of vesiculation in clathri...
Source: IET Systems Biology - October 1, 2014 Category: Biology Source Type: research
Development of a sampling-based global sensitivity analysis workflow for multiscale computational cancer models
In this study, the authors therefore propose a sampling-based GSA workflow consisting of three phases - pre-analysis, analysis and post-analysis - by integrating Monte Carlo and resampling methods with the repeated use of analysis of variance; they then exemplify this workflow using a two-dimensional multiscale lung cancer model. By accounting for all parameter rankings produced by multiple GSA methods, a summarised ranking is created at the end of the workflow based on the weighted mean of the rankings for each input parameter. For the cancer model investigated here, this analysis reveals that extracellular signal-regulat...
Source: IET Systems Biology - October 1, 2014 Category: Biology Source Type: research
Prediction of hot spots in protein interfaces using extreme learning machines with the information of spatial neighbour residues
The identification of hot spots, a small subset of protein interfaces that accounts for the majority of binding free energy, is becoming increasingly important for the research on protein-protein interaction and drug design. For each interface residue or target residue to be predicted, the authors extract hybrid features which incorporate a wide range of information of the target residue and its spatial neighbor residues, that is, the nearest contact residue in the other face (mirror-contact residue) and the nearest contact residue in the same face (intra-contact residue). Here, feature selection is performed using random ...
Source: IET Systems Biology - August 1, 2014 Category: Biology Source Type: research
Analysis and classification of DNA-binding sites in single-stranded and double-stranded DNA-binding proteins using protein information
In conclusion, the proposed features will deepen their understanding of the specificity of proteins which bind to ssDNA or dsDNA. (Source: IET Systems Biology)
Source: IET Systems Biology - August 1, 2014 Category: Biology Source Type: research
