Experimental evidence for constraints in amplitude-timescale co-variation of a biomolecular pulse generating circuit design
Understanding constraints on the functional properties of biomolecular circuit dynamics, such as the possible variations of amplitude and timescale of a pulse, is an important part of biomolecular circuit design. While the amplitude-timescale co-variations of the pulse in an incoherent feedforward loop have been investigated computationally using mathematical models, experimental support for any such constraints is relatively unclear. Here, the authors address this using experimental measurement of an existing pulse generating incoherent feedforward loop circuit realisation in the context of a standard mathematical model. ...
Source: IET Systems Biology - October 20, 2020 Category: Biology Source Type: research
Bifurcation and oscillatory dynamics of delayed CDK1-APC feedback loop
Extensive experimental evidence has been demonstrated that the dynamics of CDK1-APC feedback loop play crucial roles in regulating cell cycle processes, but the dynamical mechanisms underlying the regulation of this loop are still not completely understood. Here, the authors systematically investigated the stability and bifurcation criteria for a delayed CDK1-APC feedback loop. They showed that the maximum reaction rate of CDK1 inactivation by APC can drive sustained oscillations of CDK1 activity ($CDK1^ast $CDK1∗) and APC activity ($APC^ast $APC∗), and the amplitude of these oscillations is increasing with t...
Source: IET Systems Biology - October 16, 2020 Category: Biology Source Type: research
Identification of robust genes in transcriptional regulatory network of Mycobacterium tuberculosis
This study provides a comprehensive analysis of TRN and offers a good basis of understanding for developing experimental study in search of new therapeutic targets against MTB H37Rv pathogen. (Source: IET Systems Biology)
Source: IET Systems Biology - October 16, 2020 Category: Biology Source Type: research
Combinatorial dynamics of protein synthesis time delay and negative feedback loop in NF-κB signalling pathway
In this study, a mathematical model with IκBα protein synthesis time delay is developed based on the experimental evidences. The results show that time delay has the ability to drive oscillation of NF-κB via Hopf bifurcation. Meanwhile, the amplitude and period are sensitive to the time delay. Moreover, the time delay threshold is a function of four parameters characterising the negative feedback loop. Likewise, the parameters also have effects on the amplitude and period of NF-κB oscillation induced by time delay. Therefore, the oscillation patterns of NF-κB are collaborative results of time ...
Source: IET Systems Biology - October 16, 2020 Category: Biology Source Type: research
Formal reasoning about synthetic biology using higher-order-logic theorem proving
Synthetic biology is an interdisciplinary field that uses well-established engineering principles for performing the analysis of the biological systems, such as biological circuits, pathways, controllers and enzymes. Conventionally, the analysis of these biological systems is performed using paper-and-pencil proofs and computer simulation methods. However, these methods cannot ensure accurate results due to their inherent limitations. Higher-order-logic (HOL) theorem proving is proposed and used as a complementary approach for analysing linear biological systems, which is based on developing a mathematical model of the gen...
Source: IET Systems Biology - October 16, 2020 Category: Biology Source Type: research
Pseudo-spectral method for controlling the drug dosage in cancer
A mixed chemotherapy–immunotherapy treatment protocol is developed for cancer treatment. Chemotherapy pushes the trajectory of the system towards the desired equilibrium point, and then immunotherapy alters the dynamics of the system by affecting the parameters of the system. A co-existing cancerous equilibrium point is considered as the desired equilibrium point instead of the tumour-free equilibrium. Chemotherapy protocol is derived using the pseudo-spectral (PS) controller due to its high convergence rate and simple implementation structure. Thus, one of the contributions of this study is simplifying the design p...
Source: IET Systems Biology - October 16, 2020 Category: Biology Source Type: research
Integrated expression analysis revealed RUNX2 upregulation in lung squamous cell carcinoma tissues
This study aimed to investigate the clinicopathological significance and prospective molecular mechanism of RUNX family transcription factor 2 (RUNX2) in lung squamous cell carcinoma (LUSC). The authors used immunohistochemistry (IHC), RNA-seq, and microarray data from multi-platforms to conduct a comprehensive analysis of the clinicopathological significance and molecular mechanism of RUNX2 in the occurrence and development of LUSC. RUNX2 expression was significantly higher in 16 LUSC tissues than in paired non-cancerous tissues detected by IHC (P < 0.05). RNA-seq data from the combination of TCGA and gen...
Source: IET Systems Biology - October 16, 2020 Category: Biology Source Type: research
Design of dual hormone blood glucose therapy and comparison with single hormone using MPC algorithm
The complete automated control and delivery of insulin and glucagon in type 1 diabetes is the developing technology for artificial pancreas. This improves the quality of life of a diabetic patient with the precise infusion. The amount of infusion of these hormones is controlled using a control algorithm, which has the prediction property. The control algorithm model predictive control (MPC) predicts one step ahead and infuses the hormones continuously according to the necessity for the regulation of blood glucose. In this research, the authors propose a MPC control algorithm, which is novel for a dual hormone infusion, for...
Source: IET Systems Biology - October 16, 2020 Category: Biology Source Type: research
Estimation of skin impedance models with experimental data and a proposed model for human skin impedance
The skin is a complex biological tissue whose impedance varies with frequency. The properties and structure of skin changes with the location on the body, age, geographical location and other factors. Considering these factors, skin impedance analysis is a sophisticated data analysis. However, despite all these variations, various researchers have always worked to develop an equivalent electrical model of the skin. The two most important categories of electrical models are RC-based model and CPE-based model which focus on the physiological stratification and biological properties of skin, respectively. In this work, experi...
Source: IET Systems Biology - October 16, 2020 Category: Biology Source Type: research
Sliding mode control for a fractional-order non-linear glucose-insulin system
This study applies the sliding mode control technique and then compares the obtained simulation results with the ones obtained using feedback linearisation. (Source: IET Systems Biology)
Source: IET Systems Biology - October 16, 2020 Category: Biology Source Type: research
Efficient prediction of drug–drug interaction using deep learning models
A drug–drug interaction or drug synergy is extensively utilised for cancer treatment. However, prediction of drug–drug interaction is defined as an ill-posed problem, because manual testing is only implementable on small group of drugs. Predicting the drug–drug interaction score has been a popular research topic recently. Recently many machine learning models have proposed in the literature to predict the drug–drug interaction score efficiently. However, these models suffer from the over-fitting issue. Therefore, these models are not so-effective for predicting the drug–drug interaction s...
Source: IET Systems Biology - July 28, 2020 Category: Biology Source Type: research
Novel algebraic meal disturbance estimation based adaptive robust control design for blood glucose regulation in type 1 diabetes patients
This study designs a robust closed-loop control algorithm for elevated blood glucose level stabilisation in type 1 diabetic patients. The control algorithm is based on a novel control action resulting from integrating algebraic meal disturbance estimator with back-stepping integral sliding mode control (BISMC) technique. The estimator shows finite time convergence leading to accurate and fast estimation of meal disturbance. Moreover, compensation of the estimated disturbance in controller provides significant reduction in chattering phenomenon, which is inherent drawback of sliding mode control (SMC). The controller is app...
Source: IET Systems Biology - July 28, 2020 Category: Biology Source Type: research
Modelling and analysing biological oscillations in quorum sensing networks
Recent experiments have shown that the biological oscillation of quorum sensing (QS) system play a vital role not only in the process of bacterial synthesis but also in the treatment of cancer by releasing drugs. As known, these five substances TetR, CI, LacI, AiiA and AI are the core components of the QS system. However, the effects of AiiA and protein synthesis time delay on QS system are often ignored in the theoretical model, which is taken as a priority in the proposed research. Therefore, the authors developed a new mathematical model to explore the effects of AiiA and time delay on the dynamical behaviour of QS syst...
Source: IET Systems Biology - July 28, 2020 Category: Biology Source Type: research
Review of tools and algorithms for network motif discovery in biological networks
In this study, critical aspects of network motif discovery, design principles of background algorithms, and their functionality have been reviewed with their strengths and limitations. The performances of state-of-art algorithms are discussed in terms of runtime efficiency, scalability, and space requirement. The future scope, research direction, and challenges of the existing algorithms are presented at the end of the study. (Source: IET Systems Biology)
Source: IET Systems Biology - July 28, 2020 Category: Biology Source Type: research
eBreCaP: extreme learning-based model for breast cancer survival prediction
In this study, extreme learning machine (ELM) based model for breast cancer survival prediction named eBreCaP is proposed. It integrates the genomic (gene expression, copy number alteration, DNA methylation, protein expression) and pathological image datasets; and trains them using an ensemble of ELM with the six best-chosen models suitable to be applied on integrated data. eBreCaP has been evaluated on nine performance parameters, namely sensitivity, specificity, precision, accuracy, Matthews correlation coefficient, area under curve, area under precision–recall, hazard ratio, and concordance Index. eBreCaP has ach...
Source: IET Systems Biology - May 15, 2020 Category: Biology Source Type: research
