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

By providing the generalisation of integration and differentiation, and incorporating the memory and hereditary effects, fractional-order modelling has gotten significant attention in the past few years. One of the extensively studied and utilised models to describe the glucose–insulin system of a human body is Bergman's minimal model. This non-linear model comprises of integer-order differential equations

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

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

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

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

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

The transcription factor NF- κ B links immune response and inflammatory reaction and its different oscillation patterns determine different cell fates. In this study, a mathematical model with I κ B α 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- κ B via Hopf bifurcation. Meanwhile, the amplitude

About 30% of the world population is infected with Mycobacterium tuberculosis (MTB). It is well known that the gene expression in MTB is highly variable, thus screening of traditional single-gene in MTB has been incapable to meet the desires of clinical diagnosis. In this report, the authors systemically analysed the transcription regulatory network (TRN) in MTB H37Rv. The complex interplay of these

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

Network motifs are recurrent and over-represented patterns having biological relevance. This is one of the important local properties of biological networks. Network motif discovery finds important applications in many areas such as functional analysis of biological components, the validity of network composition, classification of networks, disease discovery, identification of unique subunits etc

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

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

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

Breast cancer is the second leading cause of death in the world. Breast cancer research is focused towards its early prediction, diagnosis, and prognosis. Breast cancer can be predicted on omics profiles, clinical tests, and pathological images. The omics profiles comprise of genomic, proteomic, and transcriptomic profiles that are available as high-dimensional datasets. Survival prediction is carried

Transdermal drug delivery is a non-invasive method of drug administration. However, to achieve this, the drug has to pass through the complicated structure of the skin. The complex structure of skin can be modelled by an electrical equivalent circuit to calculate its impedance. In this work, the transfer function of three electrical models of the human skin (Montague, Tregear and Lykken Model) based

This study elaborates on the design of artificial pancreas using model predictive control algorithm for a comprehensive physiological model such as the Sorensen model, which regulates the blood glucose and can have a longer control time in normal glycaemic region. The main objective of the proposed algorithm is to eliminate the risk of hyper and hypoglycaemia and have a precise infusion of hormones:

Biomolecular oscillators can function robustly in the presence of environmental perturbations, which can either be static or dynamic. While the effect of different circuit parameters and mechanisms on the robustness to steady perturbations has been investigated, the scenario for dynamic perturbations is relatively unclear. To address this, the authors use a benchmark three protein oscillator design

Four subtypes of breast cancer, luminal A, luminal B, basal-like, human epidermal growth factor receptor-enriched, have been identified based on gene expression profiles of human tumours. The goal of this study is to find whether the same groups' genes would exhibit different networks among the four subtypes. Differential expressed genes between each of the four subtypes and the normal samples were

Mathematical modelling is a widely used technique for describing the temporal behaviour of biological systems. One of the most challenging topics in computational systems biology is the calibration of non-linear models; i.e. the estimation of their unknown parameters. The state-of-the-art methods in this field are the frequentist and Bayesian approaches. For both of them, the performance and accuracy

Double-strand break-induced (DSB) cells send signal that induces DSBs in neighbour cells, resulting in the interaction among cells sharing the same medium. Since p53 network gives oscillatory response to DSBs, such interaction among cells could be modelled as an excitatory coupling of p53 network oscillators. This study proposes a plausible coupling model of three-mode two-dimensional oscillators,

Microarray technology plays a significant role in cancer classification, where a large number of genes and samples are simultaneously analysed. For the efficient analysis of the microarray data, there is a great demand for the development of intelligent techniques. In this article, the authors propose a novel hybrid technique employing Fisher criterion, ReliefF, and extreme learning machine (ELM) based

Cardiomyopathy (CMP) is a group of myocardial diseases that progressively impair cardiac function. The mechanisms underlying CMP development are poorly understood, but lifestyle factors are clearly implicated as risk factors. This study aimed to identify molecular biomarkers involved in inflammatory CMP development and progression using a systems biology approach. The authors analysed microarray gene

Temperature is an important determinant of bacterial growth. While the dependence of bacterial growth on different temperatures has been well studied for many bacterial species, prediction of bacterial growth rate for dynamic temperature changes is relatively unclear. Here, the authors address this issue using a combination of experimental measurements of the growth, at the resolution of 5 min, of

Regulation of hypnosis level on bi-spectral index monitor (BIS) during a surgical procedure in propofol anaesthesia administration is a challenging task for an anaesthesiologist in multi-tasking environment of the operation theater. Automation in anaesthesia has the potential to solve issues arising from manual administration. Automation in anaesthesia is based on developing the three-compartmental

ANGPTL8 is a recently identified novel hormone which regulates both glucose and lipid metabolism. The increase in ANGPTL8 during compensatory insulin resistance has been recently reported to improve glucose tolerance and a part of cytoprotective metabolic circuit. However, the exact signalling entities and dynamics involved in this process have remained elusive. Therefore, the current study was conducted

Drug sensitivity prediction is one of the critical tasks involved in drug designing and discovery. Recently several online databases and consortiums have contributed to providing open access to pharmacogenomic data. These databases have helped in developing computational approaches for drug sensitivity prediction. Cancer is a complex disease involving the heterogeneous behaviour of same tumour-type

In this study, a closed-loop control scheme is proposed for the glucose-insulin regulatory system in type-1 diabetic mellitus (T1DM) patients. Some innovative hybrid glucose-insulin regulators have combined artificial intelligence such as fuzzy logic and genetic algorithm with well known Palumbo model to regulate the blood glucose (BG) level in T1DM patients. However, most of these approaches have

In this study, a multiple-model strategy is evaluated as an alternative closed-loop method for subcutaneous insulin delivery in type 1 diabetes. Non-linearities of the glucose-insulin regulatory system are considered by modelling the system around five different operating points. After conducting some identification experiments in the UVA/Padova metabolic simulator (accepted simulator by the US Food

Driving blood glycaemia from hyperglycaemia to euglycaemia as fast as possible while avoiding hypoglycaemia is a major problem for decades for type-1 diabetes and is solved in this study. A control algorithm is designed that guaranties hypoglycaemia avoidance for the first time both from the theory of positive systems point of view and from the most pragmatic clinical practice. The solution consists

Here, a model-free controller for cancer treatment is presented. The treatment objective is to find a proper drug dosage that can reduce the population of tumour cells. Recently, some solutions have been proposed according to the control theory. In these approaches, based on the mathematical description of the number of effector cells, tumour cells, and concentration of the interleukin-2 (IL-2), a

The major intent of peptide vaccine designs, immunodiagnosis and antibody productions is to accurately identify linear B-cell epitopes. The determination of epitopes through experimental analysis is highly expensive. Therefore, it is desirable to develop a reliable model with significant improvement in prediction models. In this study, a hybrid model has been designed by using stacked generalisation

Most of the biological systems including gene regulatory networks can be described well by ordinary differential equation models with rational non-linearities. These models are derived either based on the reaction kinetics or by curve fitting to experimental data. This study demonstrates the applicability of the root-locus-based bifurcation analysis method for studying the complex dynamics of such

The emission of chlorophyll fluorescence (ChlF) from photosystem II (PSII) of plant leaves the couple with photoelectron transduction cascades in photosynthetic reactions and can be used to probe photosynthetic efficiency and plant physiology. Because of population increase, food shortages, and global warming, it is becoming more and more urgent to enhance plant photosynthesis efficiency by controlling

This manuscript discusses a competitive analysis of stochastic influenza model with constant vaccination strategy. The stochastic influenza model is comparatively more pragmatic versus the deterministic influenza model. The effect of influenza generation number holds in the stochastic model. If the value of this number is less than one, this situation will help us to control the disease in a population

This study is an attempt to explain a reliable numerical analysis of a stochastic HIV/AIDS model in a two-sex population considering counselling and antiretroviral therapy (ART). The authors are comparing the solutions of the stochastic and deterministic HIV/AIDS epidemic model. Here, an endeavour has been made to explain the stochastic HIV/AIDS epidemic model is comparatively more pragmatic in contrast

Stroke is the third major cause of mortality in the world. The diagnosis of stroke is a very complex issue considering controllable and uncontrollable factors. These factors include age, sex, blood pressure, diabetes, obesity, heart disease, smoking, and so on, having a considerable influence on the diagnosis of stroke. Hence, designing an intelligent system leading to immediate and effective treatment

Direct relationships between biological molecules connected in a gene co-expression network tend to reflect real biological activities such as gene regulation, protein-protein interactions (PPIs), and metabolisation. As correlation-based networks contain numerous indirect connections, those direct relationships are always 'hidden' in them. Compared with the global network, network communities imply

Here, the authors analyse the fractional-order predator-prey model with uncertainty, due to the vast applications in various ecological systems. The most of the ecological model do not have exact analytic solution, so they proposed a numerical technique for an approximate solution. In the proposed method, they have implemented the higher order term into the fractional Euler method to enhance the precise

In the process of drug discovery and disease treatment, drug repositioning is broadly studied to identify biological targets for existing drugs. Many methods have been proposed for drug-target interaction prediction by taking into account different kinds of data sources. However, most of the existing methods only use one side information for drugs or targets to predict new targets for drugs. Some recent

Attention deficit hyperactivity disorder (ADHD) is a common behavioural disorder that may be found in 5%-8% of the children. Early diagnosis of ADHD is crucial for treating the disease and reducing its harmful effects on education, employment, relationships, and life quality. On the other hand, non-linear analysis methods are widely applied in processing the electroencephalogram (EEG) signals. It has

This study develops an integrated model of the p53-Mdm2 interaction composed of five basic components and time delay in the DNA damage response based on the existing research work. Some critical factors, including time delay, system parameters, and their interactions in the p53-Mdm2 system are investigated to examine their effects on the oscillatory behaviour induced by Hopf bifurcation. It is shown

In humans, oxidative stress is involved in the development of diabetes, cancer, hypertension, Alzheimers' disease, and heart failure. One of the mechanisms in the cellular defence against oxidative stress is the activation of the Nrf2-antioxidant response element (ARE) signalling pathway. Computation of activity, efficacy, and potency score of ARE signalling pathway and to propose a multi-level prediction

Protein-protein interactions (PPIs) have been widely used to understand different biological processes and cellular functions associated with several diseases like cancer. Although some cancer-related protein interaction databases are available, lack of experimental data and conflicting PPI data among different available databases have slowed down the cancer research. Therefore, in this study, the

Altered miRNA expression participates in the biological progress of thyroid carcinoma and functions as a diagnostic marker or therapeutic agent. However, the role of miR-7-2-3p is currently unclear. The authors' study was the first investigation of miR-7-2-3p expression level and diagnostic ability in several public databases. Potential target genes were obtained from DIANA Tools, and function enrichment

The biological network plays a key role in protein function annotation, protein superfamily classification, disease diagnosis, etc. These networks exhibit global properties like small-world property, power-law degree distribution, hierarchical modularity, robustness, etc. Along with these, the biological network also possesses some local properties like clustering and network motif. Network motifs

A significant loss of p53 protein, an anti-tumour agent, is observed in early cancerous cells. Induction of small molecules based drug is by far the most prominent technique to revive and maintain wild-type p53 to the desired level. In this study, a sliding mode control (SMC) based robust non-linear technique is presented for the drug design of a control-oriented p53 model. The control input generated

Gene-expression data is being widely used for various clinical research. It represents expression levels of thousands of genes across the various experimental conditions simultaneously. Mining conditions specific hub genes from gene-expression data is a challenging task. Conditions specific hub genes signify the functional behaviour of bicluster across the subset of conditions and can act as prognostic

Currently, the anti-viral therapy has been extensively utilised to reduce the viral burden and switch off certain infectious sources for hepatitis B virus (HBV) infected patients in clinical treatment. Several pieces of existing evidence have demonstrated that large-scale coverage with anti-viral therapy has obtained a certain great contribution in hygiene and disease control. In this study, an anti-HBV

Although the oscillatory dynamics of the p53 network have been extensively studied, the understanding of the mechanism of delay-induced oscillations is still limited. In this paper, a comprehensive mathematical model of p53 network is studied, which contains two delayed negative feedback loops. By studying the model with and without explicit delays, the results indicate that the time delay of Mdm2

Developing a model for a signalling pathway requires several iterations of experimentation and model refinement to obtain an accurate model. However, the implementation of such an approach to model a signalling pathway induced by a poorly-known stimulus can become labour intensive because only limited information on the pathway is available beforehand to formulate an initial model. Therefore, a large

In this work, the authors propose the Hilbert transform (HT)-based numerical method to analyse the time series of the circadian rhythms. They demonstrate the application of HT by taking both deterministic and stochastic time series that they get from the simulation of the fruit fly model Drosophila melanogaster and show how to extract the period, construct phase response curves, determine period sensitivity

The authors have proposed an efficient multilevel prediction model for better activity assessment to test whether certain chemical compounds can disrupt processes in the human body that may create negative health effects. Here, a computational method (in-silico) is proposed for the quality prediction of drugs in terms of their activity, activity score, potency, and efficacy for estrogen receptors (ERs)

In this study, an automatic robust multi-objective controller has been proposed for blood glucose (BG) regulation in Type-1 Diabetic Mellitus (T1DM) patient through subcutaneous route. The main objective of this work is to control the BG level in T1DM patient in the presence of unannounced meal disturbances and other external noises with a minimum amount of insulin infusion rate. The multi-objective

Non-small cell lung cancer (NSCLC) is the most popular and dangerous type of lung cancer. Adjuvant chemotherapy (ACT) is the main treatment after surgery resection to prevent the patient from cancer recurrence. However, ACT could be toxic and unhelpful in some cases. Therefore, it is highly desired in clinical applications to predict the treatment outcomes of chemotherapy. Conventional methods of predicting

Acquired immune deficiency syndrome is an epidemic infectious disease which is caused by the human immunodeficiency virus (HIV) and that has proliferated across worldwide. It has been a matter of concern for the scientific community to develop an antiretroviral therapy, which will prompt a rapid decline in viral abundance. With this motivation, this study proposes the design of a robust super twisting

Sensitivity analysis has been widely applied to study the biological systems, including metabolic networks, signalling pathways, and genetic circuits. The Morris method is a kind of screening sensitivity analysis approach, which can fast identify a few key factors from numerous biological parameters and inputs. The parameter or input space is randomly sampled to produce a very limited number of trajectories

CO2 concentration ([CO2]) in a greenhouse may be a limiting factor for plant growth. Current greenhouse CO2 control strategy usually depends on expert experience, which may control [CO2] in a moderate range but cannot make it optimal due to lack of considering plant photochemistry reactions. A state-space kinetic model structure covering major photosynthetic reactions as affected by CO2 is useful for

This study presents a fractional-order adaptive high-gain controller for control of depth of anaesthesia. To determine the depth of anaesthesia, the bispectral index (BIS) is utilised. To attain the desired BIS, the propofol infusion rate (as the control signal) should be appropriately adjusted. The effect of the propofol on the human body is modelled with the pharmacokinetic-pharmacodynamic (PK/PD)

In human immunodeficiency virus (HIV) infection, many factors may influence the counts of healthy cells, immune cells and viruses. Drug treatment design for the HIV dynamic system is a valuable subject to be studied. This study considers an HIV dynamic system model with some unknown parameters and unmeasurable CD8 + T cell count and proposes a switching control strategy to force all states of the system