Algorithm to identify the optimal perturbation based on the net basin-of-state of perturbed states in Boolean network
Boolean networks are widely used to model gene regulatory networks and to design therapeutic intervention strategies to affect the long-term behavior of systems. Here, the authors investigate the 1 bit perturbation, which falls under the category of structural intervention. The authors' idea is that, if and only if a perturbed state evolves from a desirable attractor to an undesirable attractor or from an undesirable attractor to a desirable attractor, then the size of basin of attractor of a desirable attractor may decrease or increase. In this case, if the authors obtain the net BOS of the perturbed states, they can quic...
Source: IET Systems Biology - August 14, 2018 Category: Biology Source Type: research
Two-dimensional polynomial type canonical relaxation oscillator model for p53 dynamics
p53 network, which is responsible for DNA damage response of cells, exhibits three distinct qualitative behaviours; low state, oscillation and high state, which are associated with normal cell cycle progression, cell cycle arrest and apoptosis, respectively. The experimental studies demonstrate that these dynamics of p53 are due to the ATM and Wip1 interaction. This paper proposes a simple two-dimensional canonical relaxation oscillator model based on the identified topological structure of ATM and Wip1 interaction underlying these qualitative behaviours of p53 network. The model includes only polynomial terms that have th...
Source: IET Systems Biology - August 14, 2018 Category: Biology Source Type: research
Observer-based resilient finite-time control of blood gases model during extra-corporeal circulation
This study aims at designing an observer-based resilient controller to regulate the amount of oxygen and carbon dioxide in the blood of patients during the extra-corporeal blood circulation process. More precisely, in this study, a suitable observer-based resilient controller is constructed to regulate the levels of patient blood gases in a finite interval of time. The finite-time boundedness with the prescribed H∞ performance index of the considered blood gases control system against modelling uncertainty and external disturbances is ensured by using Lyapunov stability analysis. Moreover, a set of sufficient condit...
Source: IET Systems Biology - August 14, 2018 Category: Biology Source Type: research
Effective implicit finite-difference method for sensitivity analysis of stiff stochastic discrete biochemical systems
In this study, the authors present a novel method for estimation of sensitivity coefficients for CME models of biochemical reaction systems that span a wide range of time-scales. They make use of finite-difference approximations and adaptive implicit tau-leaping strategies to estimate sensitivities for these stiff models, resulting in significant computational efficiencies in comparison with previously published approaches of similar accuracy, as evidenced by illustrative applications. (Source: IET Systems Biology)
Source: IET Systems Biology - August 14, 2018 Category: Biology Source Type: research
Integrative computational approach to evaluate risk genes for postmenopausal osteoporosis
In recent years, numerous studies reported over a hundred of genes playing roles in the etiology of postmenopausal osteoporosis (PO). However, many of these candidate genes were lack of replication and results were not always consistent. Here, the authors proposed a computational workflow to curate and evaluate PO related genes. They integrate large-scale literature knowledge data and gene expression data (PO case/control: 10/10) for the marker evaluation. Pathway enrichment, sub-network enrichment, and gene–gene interaction analysis were conducted to study the pathogenic profile of the candidate genes, with four me...
Source: IET Systems Biology - May 15, 2018 Category: Biology Source Type: research
Structural analysis of a Petri net model of oxidative stress in atherosclerosis
In this study, a Petri net model of atherosclerosis regulation is presented. This model includes also some information about stoichiometric relationships between its components and covers all mentioned factors. For the model, a structural analysis based on invariants was made and biological conclusions are presented. Since the model contains inhibitor arcs, a heuristic method for analysis of such cases is presented. This method can be used to extend the concept of feasible t-invariants. (Source: IET Systems Biology)
Source: IET Systems Biology - May 15, 2018 Category: Biology Source Type: research
System-based strategies for p53 recovery
The authors have proposed a systems theory-based novel drug design approach for the p53 pathway. The pathway is taken as a dynamic system represented by ordinary differential equations-based mathematical model. Using control engineering practices, the system analysis and subsequent controller design is performed for the re-activation of wild-type p53. p53 revival is discussed for both modes of operation, i.e. the sustained and oscillatory. To define the problem in control system paradigm, modification in the existing mathematical model is performed to incorporate the effect of Nutlin. Attractor point analysis is carried ou...
Source: IET Systems Biology - May 15, 2018 Category: Biology Source Type: research
Describing function-based approximations of biomolecular systems
Mathematical methods provide useful framework for the analysis and design of complex systems. In newer contexts such as biology, however, there is a need to both adapt existing methods as well as to develop new ones. Using a combination of analytical and computational approaches, the authors adapt and develop the method of describing functions to represent the input–output responses of biomolecular signalling systems. They approximate representative systems exhibiting various saturating and hysteretic dynamics in a way that is better than the standard linearisation. Furthermore, they develop analytical upper bounds ...
Source: IET Systems Biology - May 15, 2018 Category: Biology Source Type: research
Review of the systems biology of the immune system using agent-based models
This study presents a review of agent-based modelling of the immune system and its interactions with the gut and lymph nodes. The authors also review the modelling of immune system interactions during tuberculosis and cancer. In addition, they also outline the future research directions for the immune system simulation through agent-based techniques such as the effects of stress on the immune system, evolution of the immune system, and identification of the parameters for a healthy immune system. (Source: IET Systems Biology)
Source: IET Systems Biology - May 15, 2018 Category: Biology Source Type: research
Adaptive non-linear control for cancer therapy through a Fokker–Planck observer
This study employs the probability density function (PDF) control approach because of its ability to control all the process moments. A Fokker–Planck-based non-linear stochastic observer will be used to determine the PDF of the process. A cost function based on the difference between a predefined desired PDF and PDF of tumour-cell population is defined. Using the proposed algorithm, the therapy function parameters are adjusted in such a manner that the cost function is minimised. The existence of an optimal therapy function is also proved. The numerical results are finally given to demonstrate the effectiveness of t...
Source: IET Systems Biology - March 16, 2018 Category: Biology Source Type: research
Evaluation of an advanced model reference sliding mode control method for cardiac assist device using a numerical model
In this study, the physiological control algorithm using sliding mode control method is implemented to track the reference input signal. The controller is developed using feed-forward part, reference model, and steady-state flow estimator. The proposed control method is evaluated using a dynamic heart-pump interaction model incorporating descriptions of the cardiovascular system – rotary blood pump. The immediate response of the controller to preload as well as afterload was studied. Stability and feasibility of the control system were demonstrated through the tests. The results showed that the present controller, w...
Source: IET Systems Biology - March 16, 2018 Category: Biology Source Type: research
Robust adaptive Lyapunov-based control of hepatitis B infection
A new robust adaptive controller is developed for the control of the hepatitis B virus (HBV) infection inside the body. The non-linear HBV model has three state variables: uninfected cells, infected cells and free viruses. A control law is designed for the antiviral therapy such that the volume of infected cells and the volume of free viruses are decreased to their desired values which are zero. One control input represents the efficiency of drug therapy in inhibiting viral production and the other control input represents the efficiency of drug therapy in blocking new infection. The proposed controller ensures the stabili...
Source: IET Systems Biology - March 16, 2018 Category: Biology Source Type: research
SMILE: a novel procedure for subcellular module identification with localisation expansion
In this study, the authors propose a novel procedure, subcellular module identification with localisation expansion (SMILE), to identify super modules that consist of several subcellular modules performing specific biological functions among cell compartments. These super modules identified by SMILE are more functionally diverse and have been verified to be more associated with known protein complexes and biological pathways compared with the modules identified from the global PPI networks in both the compartmentalised PPI and InWeb_InBioMap datasets. The authors’ results reveal that subcellular localisation is a pr...
Source: IET Systems Biology - March 16, 2018 Category: Biology Source Type: research
Overlapping functional modules detection in PPI network with pair-wise constrained non-negative matrix tri-factorisation
A large amount of available protein–protein interaction (PPI) data has been generated by high-throughput experimental techniques. Uncovering functional modules from PPI networks will help us better understand the underlying mechanisms of cellular functions. Numerous computational algorithms have been designed to identify functional modules automatically in the past decades. However, most community detection methods (non-overlapping or overlapping types) are unsupervised models, which cannot incorporate the well-known protein complexes as a priori. The authors propose a novel semi-supervised model named pairwise cons...
Source: IET Systems Biology - March 16, 2018 Category: Biology Source Type: research
Network-based method for detecting dysregulated pathways in glioblastoma cancer
The knowledge on the biological molecular mechanisms underlying cancer is important for the precise diagnosis and treatment of cancer patients. Detecting dysregulated pathways in cancer can provide insights into the mechanism of cancer and help to detect novel drug targets. Based on the wide existing mutual exclusivity among mutated genes and the interrelationship between gene mutations and expression changes, this study presents a network-based method to detect the dysregulated pathways from gene mutations and expression data of the glioblastoma cancer. First, the authors construct a gene network based on mutual exclusivi...
Source: IET Systems Biology - January 19, 2018 Category: Biology Source Type: research
