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A minimal realization technique for the dynamical structure function of a class of LTI systems Goncalves, Jorge ; ; et al in IEEE Transactions on Control of Network Systems (in press) Detailed reference viewed: 212 (10 UL)Network Identifiability from Intrinsic Noise Goncalves, Jorge ; ; in IEEE Transactions on Automatic Control (in press) Detailed reference viewed: 346 (27 UL)Causal dynamical modelling predicts novel regulatory genes of FOXP3 in human regulatory T cells Sawlekar, Rucha ; Magni, Stefano ; et al E-print/Working paper (2020) Detailed reference viewed: 34 (2 UL)High-Dimensional Kuramoto Models on Stiefel Manifolds Synchronize Complex Networks Almost Globally Markdahl, Johan ; ; Goncalves, Jorge in Automatica (2020) Detailed reference viewed: 9 (1 UL)Linear system identification from ensemble snapshot observations Aalto, Atte ; Goncalves, Jorge in Proceedings of the IEEE Conference on Decision and Control (2019, December) Developments in transcriptomics techniques have caused a large demand in tailored computational methods for modelling gene expression dynamics from experimental data. Recently, so-called single-cell ... [more ▼] Developments in transcriptomics techniques have caused a large demand in tailored computational methods for modelling gene expression dynamics from experimental data. Recently, so-called single-cell experiments have revolutionised genetic studies. These experiments yield gene expression data in single cell resolution for a large number of cells at a time. However, the cells are destroyed in the measurement process, and so the data consist of snapshots of an ensemble evolving over time, instead of time series. The problem studied in this article is how such data can be used in modelling gene regulatory dynamics. Two different paradigms are studied for linear system identification. The first is based on tracking the evolution of the distribution of cells over time. The second is based on the so-called pseudotime concept, identifying a common trajectory through the state space, along which cells propagate with different rates. Therefore, at any given time, the population contains cells in different stages of the trajectory. Resulting methods are compared in numerical experiments. [less ▲] Detailed reference viewed: 120 (21 UL)From Diagnosing Diseases to Predicting Diseases Balling, Rudi ; Goncalves, Jorge ; Magni, Stefano et al in Betz, Ulrich A.K. (Ed.) Curious2018 (2019) Chronic diseases can be considered as perturbations of complex adaptive systems. Transitions from healthy states to chronic diseases are often characterized by sudden and unexpected onset of diseases ... [more ▼] Chronic diseases can be considered as perturbations of complex adaptive systems. Transitions from healthy states to chronic diseases are often characterized by sudden and unexpected onset of diseases. These critical transitions or catastrophic shifts have been studied in theoretical and applied physics, ecology, social science, economics and recently also in biomedical applications. If we could understand the underlying mechanisms and the dynamics of critical transitions involved in the development of diseases, we would be better equipped to predict and eventually prevent them from arising. The current paper gives an overview of the potential application of the concept of critical transitions to biomedical applications. [less ▲] Detailed reference viewed: 126 (13 UL)A multifactorial evaluation framework for gene regulatory network reconstruction Mombaerts, Laurent ; Aalto, Atte ; Markdahl, Johan et al in Foundations of Systems Biology in Engineering (2019) In the past years, many computational methods have been developed to infer the structure of gene regulatory networks from time series data. However, the applicability and accuracy presumptions of such ... [more ▼] In the past years, many computational methods have been developed to infer the structure of gene regulatory networks from time series data. However, the applicability and accuracy presumptions of such algorithms remain unclear due to experimental heterogeneity. This paper assesses the performance of recent and successful network inference strategies under a novel, multifactorial evaluation framework in order to highlight pragmatic tradeoffs in experimental design. The effects of data quantity and systems perturbations are addressed, thereby formulating guidelines for efficient resource management. Realistic data were generated from six widely used benchmark models of rhythmic and nonrhythmic gene regulatory systems with random perturbations mimicking the effect of gene knock-out or chemical treatments. Then, time series data of increasing lengths were provided to five state-of-the-art network inference algorithms representing distinctive mathematical paradigms. The performances of such network reconstruction methodologies are uncovered under various experimental conditions. We report that the algorithms do not benefit equally from data increments. Furthermore, at least for the studied rhythmic system, it is more profitable for network inference strategies to be run on long time series rather than short time series with multiple perturbations. By contrast, for the non-rhythmic systems, increasing the number of perturbation experiments yielded better results than increasing the sampling frequency. We expect that future benchmark and algorithm design would integrate such multifactorial considerations to promote their widespread and conscientious usage. [less ▲] Detailed reference viewed: 33 (4 UL)Dynamical differential expression (DyDE) reveals the period control mechanisms of the Arabidopsis circadian oscillator Mombaerts, Laurent ; ; et al in PLoS Computational Biology (2019) The circadian oscillator, an internal time-keeping device found in most organisms, enables timely regulation of daily biological activities by maintaining synchrony with the external environment. The ... [more ▼] The circadian oscillator, an internal time-keeping device found in most organisms, enables timely regulation of daily biological activities by maintaining synchrony with the external environment. The mechanistic basis underlying the adjustment of circadian rhythms to changing external conditions, however, has yet to be clearly elucidated. We explored the mechanism of action of nicotinamide in Arabidopsis thaliana, a metabolite that lengthens the period of circadian rhythms, to understand the regulation of circadian period. To identify the key mechanisms involved in the circadian response to nicotinamide, we developed a systematic and practical modeling framework based on the identification and comparison of gene regulatory dynamics. Our mathematical predictions, confirmed by experimentation, identified key transcriptional regulatory mechanisms of circadian period and uncovered the role of blue light in the response of the circadian oscillator to nicotinamide. We suggest that our methodology could be adapted to predict mechanisms of drug action in complex biological systems. [less ▲] Detailed reference viewed: 91 (4 UL)Dynamic controllers for column synchronization of rotation matrices: a QR-factorization approach Thunberg, Johan ; Markdahl, Johan ; Goncalves, Jorge in Automatica (2018), 93 In the multi-agent systems setting, this paper addresses continuous-time distributed synchronization of columns of rotation matrices. More precisely, k specific columns shall be synchronized and only the ... [more ▼] In the multi-agent systems setting, this paper addresses continuous-time distributed synchronization of columns of rotation matrices. More precisely, k specific columns shall be synchronized and only the corresponding k columns of the relative rotations between the agents are assumed to be available for the control design. When one specific column is considered, the problem is equivalent to synchronization on the (d-1)-dimensional unit sphere and when all the columns are considered, the problem is equivalent to synchronization on SO(d). We design dynamic control laws for these synchronization problems. The control laws are based on the introduction of auxiliary variables in combination with a QR-factorization approach. The benefit of this QR-factorization approach is that we can decouple the dynamics for the $k$ columns from the remaining d-k ones. Under the control scheme, the closed loop system achieves almost global convergence to synchronization for quasi-strong interaction graph topologies. [less ▲] Detailed reference viewed: 126 (1 UL)Almost Global Consensus on the n-Sphere Markdahl, Johan ; Thunberg, Johan ; Goncalves, Jorge in IEEE Transactions on Automatic Control (2018), 63(6), 1664-1675 This paper establishes novel results regarding the global convergence properties of a large class of consensus protocols for multi-agent systems that evolve in continuous time on the n-dimensional unit ... [more ▼] This paper establishes novel results regarding the global convergence properties of a large class of consensus protocols for multi-agent systems that evolve in continuous time on the n-dimensional unit sphere or n-sphere. For any connected, undirected graph and all n 2 N\{1}, each protocol in said class is shown to yield almost global consensus. The feedback laws are negative gradients of Lyapunov functions and one instance generates the canonical intrinsic gradient descent protocol. This convergence result sheds new light on the general problem of consensus on Riemannian manifolds; the n-sphere for n 2 N\{1} differs from the circle and SO(3) where the corresponding protocols fail to generate almost global consensus. Moreover, we derive a novel consensus protocol on SO(3) by combining two almost globally convergent protocols on the n-sphere for n in {1, 2}. Theoretical and simulation results suggest that the combined protocol yields almost global consensus on SO(3). [less ▲] Detailed reference viewed: 101 (6 UL)Bayesian variable selection in linear dynamical systems Aalto, Atte ; Goncalves, Jorge E-print/Working paper (2018) We develop a method for reconstructing regulatory interconnection networks between variables evolving according to a linear dynamical system. The work is motivated by the problem of gene regulatory ... [more ▼] We develop a method for reconstructing regulatory interconnection networks between variables evolving according to a linear dynamical system. The work is motivated by the problem of gene regulatory network inference, that is, finding causal effects between genes from gene expression time series data. In biological applications, the typical problem is that the sampling frequency is low, and consequentially the system identification problem is ill-posed. The low sampling frequency also makes it impossible to estimate derivatives directly from the data. We take a Bayesian approach to the problem, as it offers a natural way to incorporate prior information to deal with the ill-posedness, through the introduction of sparsity promoting prior for the underlying dynamics matrix. It also provides a framework for modelling both the process and measurement noises. We develop Markov Chain Monte Carlo samplers for the discrete-valued zero-structure of the dynamics matrix, and for the continuous-time trajectory of the system. [less ▲] Detailed reference viewed: 109 (11 UL)Towards almost global synchronization on the Stiefel manifold Markdahl, Johan ; ; Goncalves, Jorge in Proceedings of the 57th IEEE Conference on Decision and Control (2018) Detailed reference viewed: 6 (0 UL)A lifting method for analyzing distributed synchronization on the unit sphere Thunberg, Johan ; Markdahl, Johan ; et al in Automatica (2018) This paper introduces a new lifting method for analyzing convergence of continuous-time distributed synchronization/consensus systems on the unit sphere. Points on the d-dimensional unit sphere are lifted ... [more ▼] This paper introduces a new lifting method for analyzing convergence of continuous-time distributed synchronization/consensus systems on the unit sphere. Points on the d-dimensional unit sphere are lifted to the (d+1)-dimensional Euclidean space. The consensus protocol on the unit sphere is the classical one, where agents move toward weighted averages of their neighbors in their respective tangent planes. Only local and relative state information is used. The directed interaction graph topologies are allowed to switch as a function of time. The dynamics of the lifted variables are governed by a nonlinear consensus protocol for which the weights contain ratios of the norms of state variables. We generalize previous convergence results for hemispheres. For a large class of consensus protocols defined for switching uniformly quasi-strongly connected time-varying graphs, we show that the consensus manifold is uniformly asymptotically stable relative to closed balls contained in a hemisphere. Compared to earlier projection based approaches used in this context such as the gnomonic projection, which is defined for hemispheres only, the lifting method applies globally. With that, the hope is that this method can be useful for future investigations on global convergence. [less ▲] Detailed reference viewed: 68 (0 UL)PaCER - A fully automated method for electrode trajectory and contact reconstruction in deep brain stimulation Husch, Andreas ; ; et al in NeuroImage: Clinical (2018), 17 Abstract Deep brain stimulation (DBS) is a neurosurgical intervention where electrodes are permanently implanted into the brain in order to modulate pathologic neural activity. The post-operative ... [more ▼] Abstract Deep brain stimulation (DBS) is a neurosurgical intervention where electrodes are permanently implanted into the brain in order to modulate pathologic neural activity. The post-operative reconstruction of the DBS electrodes is important for an efficient stimulation parameter tuning. A major limitation of existing approaches for electrode reconstruction from post-operative imaging that prevents the clinical routine use is that they are manual or semi-automatic, and thus both time-consuming and subjective. Moreover, the existing methods rely on a simplified model of a straight line electrode trajectory, rather than the more realistic curved trajectory. The main contribution of this paper is that for the first time we present a highly accurate and fully automated method for electrode reconstruction that considers curved trajectories. The robustness of our proposed method is demonstrated using a multi-center clinical dataset consisting of N=44 electrodes. In all cases the electrode trajectories were successfully identified and reconstructed. In addition, the accuracy is demonstrated quantitatively using a high-accuracy phantom with known ground truth. In the phantom experiment, the method could detect individual electrode contacts with high accuracy and the trajectory reconstruction reached an error level below 100 μm (0.046 ± 0.025 mm). An implementation of the method is made publicly available such that it can directly be used by researchers or clinicians. This constitutes an important step towards future integration of lead reconstruction into standard clinical care. [less ▲] Detailed reference viewed: 176 (30 UL)Post-operative deep brain stimulation assessment: Automatic data integration and report generation Husch, Andreas ; ; et al in Brain Stimulation (2018) Background The gold standard for post-operative deep brain stimulation (DBS) parameter tuning is a monopolar review of all stimulation contacts, a strategy being challenged by recent developments of more ... [more ▼] Background The gold standard for post-operative deep brain stimulation (DBS) parameter tuning is a monopolar review of all stimulation contacts, a strategy being challenged by recent developments of more complex electrode leads. Objective Providing a method to guide clinicians on DBS assessment and parameter tuning by automatically integrating patient individual data. Methods We present a fully automatic method for visualization of individual deep brain structures in relation to a DBS lead by combining precise electrode recovery from post-operative imaging with individual estimates of deep brain morphology utilizing a 7T-MRI deep brain atlas. Results The method was evaluated on 20 STN DBS cases. It demonstrated robust automatic creation of 3D-enabled PDF reports visualizing electrode to brain structure relations and proved valuable in detecting miss placed electrodes. Discussion Automatic DBS assessment is feasible and can conveniently provide clinicians with relevant information on DBS contact positions in relation to important anatomical structures. [less ▲] Detailed reference viewed: 120 (7 UL)Continuous time Gaussian process dynamical models in gene regulatory network inference Aalto, Atte ; ; et al E-print/Working paper (2018) One of the focus areas of modern scientific research is to reveal mysteries related to genes and their interactions. The dynamic interactions between genes can be encoded into a gene regulatory network ... [more ▼] One of the focus areas of modern scientific research is to reveal mysteries related to genes and their interactions. The dynamic interactions between genes can be encoded into a gene regulatory network (GRN), which can be used to gain understanding on the genetic mechanisms behind observable phenotypes. GRN inference from time series data has recently been a focus area of systems biology. Due to low sampling frequency of the data, this is a notoriously difficult problem. We tackle the challenge by introducing the so-called continuous-time Gaussian process dynamical model (GPDM), based on Gaussian process framework that has gained popularity in nonlinear regression problems arising in machine learning. The model dynamics are governed by a stochastic differential equation, where the dynamics function is modelled as a Gaussian process. We prove the existence and uniqueness of solutions of the stochastic differential equation. We derive the probability distribution for the Euler discretised trajectories and establish the convergence of the discretisation. We develop a GRN inference method based on the developed framework. The method is based on MCMC sampling of trajectories of the GPDM and estimating the hyperparameters of the covariance function of the Gaussian process. Using benchmark data examples, we show that our method is computationally feasible and superior in dealing with poor time resolution. [less ▲] Detailed reference viewed: 59 (6 UL)On definition and inference of nonlinear Boolean dynamic networks Yue, Zuogong ; Thunberg, Johan ; et al in On definition and inference of nonlinear Boolean dynamic networks (2017, December) Network reconstruction has become particularly important in systems biology, and is now expected to deliver information on causality. Systems in nature are inherently nonlinear. However, for nonlinear ... [more ▼] Network reconstruction has become particularly important in systems biology, and is now expected to deliver information on causality. Systems in nature are inherently nonlinear. However, for nonlinear dynamical systems with hidden states, how to give a useful definition of dynamic networks is still an open question. This paper presents a useful definition of Boolean dynamic networks for a large class of nonlinear systems. Moreover, a robust inference method is provided. The well-known Millar-10 model in systems biology is used as a numerical example, which provides the ground truth of causal networks for key mRNAs involved in eukaryotic circadian clocks. In addition, as second contribution of this paper, we suggest definitions of linear network identifiability, which helps to unify the available work on network identifiability. [less ▲] Detailed reference viewed: 132 (5 UL)Experimental design trade-offs for gene regulatory network inference: an in silico study of the yeast Saccharomyces cerevisiae cell cycle Markdahl, Johan ; Colombo, Nicolo ; Thunberg, Johan et al in Proceedings of the 56th IEEE Conference on Decision and Control (2017, December) Time-series of high throughput gene sequencing data intended for gene regulatory network (GRN) inference are often short due to the high costs of sampling cell systems. Moreover, experimentalists lack a ... [more ▼] Time-series of high throughput gene sequencing data intended for gene regulatory network (GRN) inference are often short due to the high costs of sampling cell systems. Moreover, experimentalists lack a set of quantitative guidelines that prescribe the minimal number of samples required to infer a reliable GRN model. We study the temporal resolution of data vs.quality of GRN inference in order to ultimately overcome this deficit. The evolution of a Markovian jump process model for the Ras/cAMP/PKA pathway of proteins and metabolites in the G1 phase of the Saccharomyces cerevisiae cell cycle is sampled at a number of different rates. For each time-series we infer a linear regression model of the GRN using the LASSO method. The inferred network topology is evaluated in terms of the area under the precision-recall curve (AUPR). By plotting the AUPR against the number of samples, we show that the trade-off has a, roughly speaking, sigmoid shape. An optimal number of samples corresponds to values on the ridge of the sigmoid. [less ▲] Detailed reference viewed: 109 (10 UL)Distributed synchronization of euclidean transformations with guaranteed convergence Thunberg, Johan ; Goncalves, Jorge ; in 56th IEEE Conference on Decision and Control (2017, December) This paper addresses synchronization of Euclidean transformations over graphs. Synchronization in this context, unlike rendezvous or consensus, means that composite transformations over loops in the graph ... [more ▼] This paper addresses synchronization of Euclidean transformations over graphs. Synchronization in this context, unlike rendezvous or consensus, means that composite transformations over loops in the graph are equal to the identity. Given a set of non-synchronized transformations, the problem at hand is to find a set of synchronized transformations approximating well the non-synchronized transformations. This is formulated as a nonlinear least-squares optimization problem. We present a distributed synchronization algorithm that converges to the optimal solution to an approximation of the optimization problem. This approximation stems from a spectral relaxation of the rotational part on the one hand and from a separation between the rotations and the translations on the other. The method can be used to distributively improve the measurements obtained in sensor networks such as networks of cameras where pairwise relative transformations are measured. The convergence of the method is verified in numerical simulations. [less ▲] Detailed reference viewed: 74 (1 UL)Distributed methods for synchronization of orthogonal matrices over graphs Thunberg, Johan ; Bernard, Florian ; Goncalves, Jorge in Automatica (2017), 80 This paper addresses the problem of synchronizing orthogonal matrices over directed graphs. For synchronized transformations (or matrices), composite transformations over loops equal the identity. We ... [more ▼] This paper addresses the problem of synchronizing orthogonal matrices over directed graphs. For synchronized transformations (or matrices), composite transformations over loops equal the identity. We formulate the synchronization problem as a least-squares optimization problem with nonlinear constraints. The synchronization problem appears as one of the key components in applications ranging from 3D-localization to image registration. The main contributions of this work can be summarized as the introduction of two novel algorithms; one for symmetric graphs and one for graphs that are possibly asymmetric. Under general conditions, the former has guaranteed convergence to the solution of a spectral relaxation to the synchronization problem. The latter is stable for small step sizes when the graph is quasi-strongly connected. The proposed methods are verified in numerical simulations. [less ▲] Detailed reference viewed: 99 (3 UL) |
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