Network analysis of complex biological systems : boundedness of weakly reversible chemical reaction networks and conditions for synchronisation of coupled oscillators

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Inverse problems from biomedicine: Inference of putative disease mechanisms and robust therapeutic strategies

Many complex diseases that are difficult to treat cannot be mapped onto a single cause, but arise from the interplay of multiple contributing factors. In the study of such diseases, it is becoming apparent that therapeutic strategies targeting a single protein or metabolite are often not efficacious. Rather, a systems perspective describing the interaction of physiological components is needed. In this paper, we demonstrate via examples of disease models the kind of inverse problems that arise from the need to infer disease mechanisms and/or therapeutic strategies. We identify the challenges that arise, in particular the need to devise strategies that are robust against variable physiological states and parametric uncertaintie

Determining Asymptotic Stability and Robustness of Networked Systems

Publisher's version (útgefin grein)This paper is motivated by the notion that coupling systems allows for mitigating the failure of individual ones. We present a novel approach to determining asymptotic stability and robustness of a network consisting of coupled dynamical systems, where individual system dynamics are represented through polynomial or rational functions. The analysis relies on a local analysis; thus, making it computationally implementable. We present an efficient computational method that relies on semidefinite programming. Importantly, for cases where multiple equilibrium points exist, we show how to determine regions around an asymptotically stable equilibrium point that bounds solutions. These regions increase when systems are coupled as we observe when applying the presented analysis framework to a mathematical model of a continuous stirred tank reactor. Importantly, the presented work has implications to other fields as well."Peer Reviewed

Sufficient Stability Conditions for a Class of Switched Systems with Multiple Steady States

In this paper, we present a novel approach to determine the stability of switched linear and nonlinear systems using Sum of Squares optimisation. Particularly, we use Sum of Squares optimisation to search for a Lyapunov function that defines an absorbing set that confines solution trajectories. For linear systems, we show that this also implies global asymptotic stability. Using this approach, we can study stability for a broader range of switched systems, particularly, we can search for a global attractor for switched nonlinear systems, whose dynamics are given by polynomial vector fields and which have multiple equilibria or limit cycles.Comment: Accepted in IEEE Control Systems Letter, to appea

Discriminating between rival biochemical network models: three approaches to optimal experiment design

Background: The success of molecular systems biology hinges on the ability to use computational models to design predictive experiments, and ultimately unravel underlying biological mechanisms. A problem commonly encountered in the computational modelling of biological networks is that alternative, structurally different models of similar complexity fit a set of experimental data equally well. In this case, more than one molecular mechanism can explain available data. In order to rule out the incorrect mechanisms, one needs to invalidate incorrect models. At this point, new experiments maximizing the difference between the measured values of alternative models should be proposed and conducted. Such experiments should be optimally designed to produce data that are most likely to invalidate incorrect model structures. Results: In this paper we develop methodologies for the optimal design of experiments with the aim of discriminating between different mathematical models of the same biological system. The first approach determines the 'best' initial condition that maximizes the L2 (energy) distance between the outputs of the rival models. In the second approach, we maximize the L2-distance of the outputs by designing the optimal external stimulus (input) profile of unit L2-norm. Our third method uses optimized structural changes (corresponding, for example, to parameter value changes reflecting gene knock-outs) to achieve the same goal. The numerical implementation of each method is considered in an example, signal processing in starving Dictyostelium amœbæ. Conclusions: Model-based design of experiments improves both the reliability and the efficiency of biochemical network model discrimination. This opens the way to model invalidation, which can be used to perfect our understanding of biochemical networks. Our general problem formulation together with the three proposed experiment design methods give the practitioner new tools for a systems biology approach to experiment design. </p

Hyperhidrosis in sleep disorders – A narrative review of mechanisms and clinical significance

Funding Information: Grant Fondecyt 1211443 Publisher Copyright: © 2022 European Sleep Research Society.Hyperhidrosis is characterized by excessive sweating beyond thermoregulatory needs that affects patients' quality of life. It results from an excessive stimulation of eccrine sweat glands in the skin by the sympathetic nervous system. Hyperhidrosis may be primary or secondary to an underlying cause. Nocturnal hyperhidrosis is associated with different sleep disorders, such as obstructive sleep apnea, insomnia, restless legs syndrome/periodic limb movement during sleep and narcolepsy. The major cause of the hyperhidrosis is sympathetic overactivity and, in the case of narcolepsy type 1, orexin deficiency may also contribute. In this narrative review, we will provide an outline of the possible mechanisms underlying sudomotor dysfunction and the resulting nocturnal hyperhidrosis in these different sleep disorders and explore its clinical relevance.Peer reviewe

Importance of getting enough sleep and daily activity data to assess variability : longitudinal observational study

Background: The gold standard measurement for recording sleep is polysomnography performed in a hospital environment for 1 night. This requires individuals to sleep with a device and several sensors attached to their face, scalp, and body, which is both cumbersome and expensive. Self-trackers, such as wearable sensors (eg, smartwatch) and nearable sensors (eg, sleep mattress), can measure a broad range of physiological parameters related to free-living sleep conditions; however, the optimal duration of such a self-tracker measurement is not known. For such free-living sleep studies with actigraphy, 3 to 14 days of data collection are typically used. Objective: The primary goal of this study is to investigate if 3 to 14 days of sleep data collection is sufficient while using self-trackers. The secondary goal is to investigate whether there is a relationship among sleep quality, physical activity, and heart rate. Specifically, we study whether individuals who exhibit similar activity can be clustered together and to what extent the sleep patterns of individuals in relation to seasonality vary. Methods: Data on sleep, physical activity, and heart rate were collected over 6 months from 54 individuals aged 52 to 86 years. The Withings Aura sleep mattress (nearable; Withings Inc) and Withings Steel HR smartwatch (wearable; Withings Inc) were used. At the individual level, we investigated the consistency of various physical activities and sleep metrics over different time spans to illustrate how sensor data from self-trackers can be used to illuminate trends. We used exploratory data analysis and unsupervised machine learning at both the cohort and individual levels. Results: Significant variability in standard metrics of sleep quality was found between different periods throughout the study. We showed specifically that to obtain more robust individual assessments of sleep and physical activity patterns through self-trackers, an evaluation period of >3 to 14 days is necessary. In addition, we found seasonal patterns in sleep data related to the changing of the clock for daylight saving time. Conclusions: We demonstrate that >2 months' worth of self-tracking data are needed to provide a representative summary of daily activity and sleep patterns. By doing so, we challenge the current standard of 3 to 14 days for sleep quality assessment and call for the rethinking of standards when collecting data for research purposes. Seasonal patterns and daylight saving time clock change are also important aspects that need to be taken into consideration when choosing a period for collecting data and designing studies on sleep. Furthermore, we suggest using self-trackers (wearable and nearable ones) to support longer-term evaluations of sleep and physical activity for research purposes and, possibly, clinical purposes in the future

Automatic Detection of Electrodermal Activity Events during Sleep

Publisher Copyright: © 2023 by the authors.Currently, there is significant interest in developing algorithms for processing electrodermal activity (EDA) signals recorded during sleep. The interest is driven by the growing popularity and increased accuracy of wearable devices capable of recording EDA signals. If properly processed and analysed, they can be used for various purposes, such as identifying sleep stages and sleep-disordered breathing, while being minimally intrusive. Due to the tedious nature of manually scoring EDA sleep signals, the development of an algorithm to automate scoring is necessary. In this paper, we present a novel scoring algorithm for the detection of EDA events and EDA storms using signal processing techniques. We apply the algorithm to EDA recordings from two different and unrelated studies that have also been manually scored and evaluate its performances in terms of precision, recall, and (Formula presented.) score. We obtain (Formula presented.) scores of about 69% for EDA events and of about 56% for EDA storms. In comparison to the literature values for scoring agreement between experts, we observe a strong agreement between automatic and manual scoring of EDA events and a moderate agreement between automatic and manual scoring of EDA storms. EDA events and EDA storms detected with the algorithm can be further processed and used as training variables in machine learning algorithms to classify sleep health.Peer reviewe