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Mauricio Barahona

Publications and source records attributed to Mauricio Barahona.

At least 91 records · Page 5Linked to original sources

The 'who' and 'what' of #diabetes on Twitter

Social media are being increasingly used for health promotion, yet the landscape of users, messages and interactions in such fora is poorly understood. Studies of social media and diabetes have focused mostly on patients, or public agencies addressing it, but have not looked broadly at all the participants or the diversity of content they contribute. We study Twitter conversations about diabetes through the systematic analysis of 2.5 million tweets collected over 8 months and the interactions between their authors. We address three questions: (1) what themes arise in these tweets?, (2) who are the most influential users?, (3) which type of users contribute to which themes? We answer these questions using a mixed-methods approach, integrating techniques from anthropology, network science and information retrieval such as thematic coding, temporal network analysis, and community and topic detection. Diabetes-related tweets fall within broad thematic groups: health information, news, social interaction, and commercial. At the same time, humorous messages and references to popular culture appear consistently, more than any other type of tweet. We classify authors according to their temporal 'hub' and 'authority' scores. Whereas the hub landscape is diffuse and fluid over time, top authorities are highly persistent across time and comprise bloggers, advocacy groups and NGOs related to diabetes, as well as for-profit entities without specific diabetes expertise. Top authorities fall into seven interest communities as derived from their Twitter follower network. Our findings have implications for public health professionals and policy makers who seek to use social media as an engagement tool and to inform policy design.

physics.soc-ph↗

Stochastic models of gene transcription with upstream drives: exact solution and sample path characterization

Gene transcription is a highly stochastic and dynamic process. As a result, the mRNA copy number of a given gene is heterogeneous both between cells and across time. We present a framework to model gene transcription in populations of cells with time-varying (stochastic or deterministic) transcription and degradation rates. Such rates can be understood as upstream cellular drives representing the effect of different aspects of the cellular environment. We show that the full solution of the master equation contains two components: a model-specific, upstream effective drive, which encapsulates the effect of cellular drives (e.g., entrainment, periodicity or promoter randomness), and a downstream transcriptional Poissonian part, which is common to all models. Our analytical framework treats cell-to-cell and dynamic variability consistently, unifying several approaches in the literature. We apply the obtained solution to characterise different models of experimental relevance, and to explain the influence on gene transcription of synchrony, stationarity, ergodicity, as well as the effect of time-scales and other dynamic characteristics of drives. We also show how the solution can be applied to the analysis of noise sources in single-cell data, and to reduce the computational cost of stochastic simulations.

q-bio.QM↗

Linear models of activation cascades: analytical solutions and coarse-graining of delayed signal transduction

Cellular signal transduction usually involves activation cascades, the sequential activation of a series of proteins following the reception of an input signal. Here we study the classic model of weakly activated cascades and obtain analytical solutions for a variety of inputs. We show that in the special but important case of optimal-gain cascades (i.e., when the deactivation rates are identical) the downstream output of the cascade can be represented exactly as a lumped nonlinear module containing an incomplete gamma function with real parameters that depend on the rates and length of the cascade, as well as parameters of the input signal. The expressions obtained can be applied to the non-identical case when the deactivation rates are random to capture the variability in the cascade outputs. We also show that cascades can be rearranged so that blocks with similar rates can be lumped and represented through our nonlinear modules. Our results can be used both to represent cascades in computational models of differential equations and to fit data efficiently, by reducing the number of equations and parameters involved. In particular, the length of the cascade appears as a real-valued parameter and can thus be fitted in the same manner as Hill coefficients. Finally, we show how the obtained nonlinear modules can be used instead of delay differential equations to model delays in signal transduction.

q-bio.MN↗

Graph partitions and cluster synchronization in networks of oscillators

Synchronization over networks depends strongly on the structure of the coupling between the oscillators. When the coupling presents certain regularities, the dynamics can be coarse-grained into clusters by means of External Equitable Partitions of the network graph and their associated quotient graphs. We exploit this graph-theoretical concept to study the phenomenon of cluster synchronization, in which different groups of nodes converge to distinct behaviors. We derive conditions and properties of networks in which such clustered behavior emerges, and show that the ensuing dynamics is the result of the localization of the eigenvectors of the associated graph Laplacians linked to the existence of invariant subspaces. The framework is applied to both linear and non-linear models, first for the standard case of networks with positive edges, before being generalized to the case of signed networks with both positive and negative interactions. We illustrate our results with examples of both signed and unsigned graphs for consensus dynamics and for partial synchronization of oscillator networks under the master stability function as well as Kuramoto oscillators.

physics.soc-ph↗

Flow-based network analysis of the Caenorhabditis elegans connectome

We exploit flow propagation on the directed neuronal network of the nematode Caenorhabditis elegans to reveal dynamically relevant features of its connectome. We find flow-based groupings of neurons at different levels of granularity, which we relate to functional and anatomical constituents of its nervous system. A systematic in silico evaluation of the full set of single and double neuron ablations is used to identify deletions that induce the most severe disruptions of the multi-resolution flow structure. Such ablations are linked to functionally relevant neurons, and suggest potential candidates for further in vivo investigation. In addition, we use the directional patterns of incoming and outgoing network flows at all scales to identify flow profiles for the neurons in the connectome, without pre-imposing a priori categories. The four flow roles identified are linked to signal propagation motivated by biological input-response scenarios.

q-bio.NC↗

Bounding stationary averages of polynomial diffusions via semidefinite programming

We introduce an algorithm based on semidefinite programming that yields increasing (resp. decreasing) sequences of lower (resp. upper) bounds on polynomial stationary averages of diffusions with polynomial drift vector and diffusion coefficients. The bounds are obtained by optimising an objective, determined by the stationary average of interest, over the set of real vectors defined by certain linear equalities and semidefinite inequalities which are satisfied by the moments of any stationary measure of the diffusion. We exemplify the use of the approach through several applications: a Bayesian inference problem; the computation of Lyapunov exponents of linear ordinary differential equations perturbed by multiplicative white noise; and a reliability problem from structural mechanics. Additionally, we prove that the bounds converge to the infimum and supremum of the set of stationary averages for certain SDEs associated with the computation of the Lyapunov exponents, and we provide numerical evidence of convergence in more general settings.

math.PR↗

Prediction of allosteric sites and mediating interactions through bond-to-bond propensities

Allosteric regulation is central to many biochemical processes. Allosteric sites provide a target to fine-tune protein activity, yet we lack computational methods to predict them. Here, we present an efficient graph-theoretical approach for identifying allosteric sites and the mediating interactions that connect them to the active site. Using an atomistic graph with edges weighted by covalent and non-covalent bond energies, we obtain a bond-to-bond propensity that quantifies the effect of instantaneous bond fluctuations propagating through the protein. We use this propensity to detect the sites and communication pathways most strongly linked to the active site, assessing their significance through quantile regression and comparison against a reference set of 100 generic proteins. We exemplify our method in detail with three well-studied allosteric proteins: caspase-1, CheY, and h-Ras, correctly predicting the location of the allosteric site and identifying key allosteric interactions. Consistent prediction of allosteric sites is then attained in a further set of 17 proteins known to exhibit allostery. Because our propensity measure runs in almost linear time, it offers a scalable approach to high-throughput searches for candidate allosteric sites.

q-bio.BM↗

Window functions and sigmoidal behaviour of memristive systems

A common approach to model memristive systems is to include empirical window functions to describe edge effects and non-linearities in the change of the memristance. We demonstrate that under quite general conditions, each window function can be associated with a sigmoidal curve relating the normalised time-dependent memristance to the time integral of the input. Conversely, this explicit relation allows us to derive window functions suitable for the mesoscopic modelling of memristive systems from a variety of well-known sigmoidals. Such sigmoidal curves are defined in terms of measured variables and can thus be extracted from input and output signals of a device and then transformed to its corresponding window. We also introduce a new generalised window function that allows the flexible modelling of asymmetric edge effects in a simple manner.

cond-mat.mes-hall↗

Great cities look small

Great cities connect people; failed cities isolate people. Despite the fundamental importance of physical, face-to-face social-ties in the functioning of cities, these connectivity networks are not explicitly observed in their entirety. Attempts at estimating them often rely on unrealistic over-simplifications such as the assumption of spatial homogeneity. Here we propose a mathematical model of human interactions in terms of a local strategy of maximising the number of beneficial connections attainable under the constraint of limited individual travelling-time budgets. By incorporating census and openly-available online multi-modal transport data, we are able to characterise the connectivity of geometrically and topologically complex cities. Beyond providing a candidate measure of greatness, this model allows one to quantify and assess the impact of transport developments, population growth, and other infrastructure and demographic changes on a city. Supported by validations of GDP and HIV infection rates across United States metropolitan areas, we illustrate the effect of changes in local and city-wide connectivities by considering the economic impact of two contemporary inter- and intra-city transport developments in the United Kingdom: High Speed Rail 2 and London Crossrail. This derivation of the model suggests that the scaling of different urban indicators with population size has an explicitly mechanistic origin.

physics.soc-ph↗

Emergence of slow-switching assemblies in structured neuronal networks

Unraveling the interplay between connectivity and spatio-temporal dynamics in neuronal networks is a key step to advance our understanding of neuronal information processing. Here we investigate how particular features of network connectivity underpin the propensity of neural networks to generate slow-switching assembly (SSA) dynamics, i.e., sustained epochs of increased firing within assemblies of neurons which transition slowly between different assemblies throughout the network. We show that the emergence of SSA activity is linked to spectral properties of the asymmetric synaptic weight matrix. In particular, the leading eigenvalues that dictate the slow dynamics exhibit a gap with respect to the bulk of the spectrum, and the associated Schur vectors exhibit a measure of block-localization on groups of neurons, thus resulting in coherent dynamical activity on those groups. Through simple rate models, we gain analytical understanding of the origin and importance of the spectral gap, and use these insights to develop new network topologies with alternative connectivity paradigms which also display SSA activity. Specifically, SSA dynamics involving excitatory and inhibitory neurons can be achieved by modifying the connectivity patterns between both types of neurons. We also show that SSA activity can occur at multiple timescales reflecting a hierarchy in the connectivity, and demonstrate the emergence of SSA in small-world like networks. Our work provides a step towards understanding how network structure (uncovered through advancements in neuroanatomy and connectomics) can impact on spatio-temporal neural activity and constrain the resulting dynamics.

q-bio.NC↗

Toggling a Genetic Switch Using Reinforcement Learning

In this paper, we consider the problem of optimal exogenous control of gene regulatory networks. Our approach consists in adapting an established reinforcement learning algorithm called the fitted Q iteration. This algorithm infers the control law directly from the measurements of the system's response to external control inputs without the use of a mathematical model of the system. The measurement data set can either be collected from wet-lab experiments or artificially created by computer simulations of dynamical models of the system. The algorithm is applicable to a wide range of biological systems due to its ability to deal with nonlinear and stochastic system dynamics. To illustrate the application of the algorithm to a gene regulatory network, the regulation of the toggle switch system is considered. The control objective of this problem is to drive the concentrations of two specific proteins to a target region in the state space.

eess.SY↗

Dynamics of Cluster Synchronisation in Modular Networks: Implications for Structural and Functional Networks

Experimental results often do not assess network structure; rather, the network structure is inferred by the dynamics of the nodes. From the dynamics of the nodes one then constructs a network of functional relations, termed the functional network. A fundamental question in the analysis of complex systems concerns the relation between functional and structural networks. Using synchronisation as a paradigm for network functionality, we study the dynamics of cluster formation in functional networks. We show that the functional network can drastically differ from the structural network. We uncover the mechanism driving these bifurcations by obtaining necessary conditions for modular synchronisation.

nlin.AO↗

Revealing cell assemblies at multiple levels of granularity

Background: Current neuronal monitoring techniques, such as calcium imaging and multi-electrode arrays, enable recordings of spiking activity from hundreds of neurons simultaneously. Of primary importance in systems neuroscience is the identification of cell assemblies: groups of neurons that cooperate in some form within the recorded population. New Method: We introduce a simple, integrated framework for the detection of cell-assemblies from spiking data without a priori assumptions about the size or number of groups present. We define a biophysically-inspired measure to extract a directed functional connectivity matrix between both excitatory and inhibitory neurons based on their spiking history. The resulting network representation is analyzed using the Markov Stability framework, a graph theoretical method for community detection across scales, to reveal groups of neurons that are significantly related in the recorded time-series at different levels of granularity. Results and comparison with existing methods: Using synthetic spike-trains, including simulated data from leaky-integrate-and-fire networks, our method is able to identify important patterns in the data such as hierarchical structure that are missed by other standard methods. We further apply the method to experimental data from retinal ganglion cells of mouse and salamander, in which we identify cell-groups that correspond to known functional types, and to hippocampal recordings from rats exploring a linear track, where we detect place cells with high fidelity. Conclusions: We present a versatile method to detect neural assemblies in spiking data applicable across a spectrum of relevant scales that contributes to understanding spatio-temporal information gathered from systems neuroscience experiments.

q-bio.NC↗

Interest communities and flow roles in directed networks: the Twitter network of the UK riots

Directionality is a crucial ingredient in many complex networks in which information, energy or influence are transmitted. In such directed networks, analysing flows (and not only the strength of connections) is crucial to reveal important features of the network that might go undetected if the orientation of connections is ignored. We showcase here a flow-based approach for community detection in networks through the study of the network of the most influential Twitter users during the 2011 riots in England. Firstly, we use directed Markov Stability to extract descriptions of the network at different levels of coarseness in terms of interest communities, i.e., groups of nodes within which flows of information are contained and reinforced. Such interest communities reveal user groupings according to location, profession, employer, and topic. The study of flows also allows us to generate an interest distance, which affords a personalised view of the attention in the network as viewed from the vantage point of any given user. Secondly, we analyse the profiles of incoming and outgoing long-range flows with a combined approach of role-based similarity and the novel relaxed minimum spanning tree algorithm to reveal that the users in the network can be classified into five roles. These flow roles go beyond the standard leader/follower dichotomy and differ from classifications based on regular/structural equivalence. We then show that the interest communities fall into distinct informational organigrams characterised by a different mix of user roles reflecting the quality of dialogue within them. Our generic framework can be used to provide insight into how flows are generated, distributed, preserved and consumed in directed networks.

physics.soc-ph↗

Structure of complex networks: Quantifying edge-to-edge relations by failure-induced flow redistribution

The analysis of complex networks has so far revolved mainly around the role of nodes and communities of nodes. However, the dynamics of interconnected systems is commonly focalised on edge processes, and a dual edge-centric perspective can often prove more natural. Here we present graph-theoretical measures to quantify edge-to-edge relations inspired by the notion of flow redistribution induced by edge failures. Our measures, which are related to the pseudo-inverse of the Laplacian of the network, are global and reveal the dynamical interplay between the edges of a network, including potentially non-local interactions. Our framework also allows us to define the embeddedness of an edge, a measure of how strongly an edge features in the weighted cuts of the network. We showcase the general applicability of our edge-centric framework through analyses of the Iberian Power grid, traffic flow in road networks, and the C. elegans neuronal network.

physics.soc-ph↗

Finding role communities in directed networks using Role-Based Similarity, Markov Stability and the Relaxed Minimum Spanning Tree

We present a framework to cluster nodes in directed networks according to their roles by combining Role-Based Similarity (RBS) and Markov Stability, two techniques based on flows. First we compute the RBS matrix, which contains the pairwise similarities between nodes according to the scaled number of in- and out-directed paths of different lengths. The weighted RBS similarity matrix is then transformed into an undirected similarity network using the Relaxed Minimum-Spanning Tree (RMST) algorithm, which uses the geometric structure of the RBS matrix to unblur the network, such that edges between nodes with high, direct RBS are preserved. Finally, we partition the RMST similarity network into role-communities of nodes at all scales using Markov Stability to find a robust set of roles in the network. We showcase our framework through a biological and a man-made network.

cs.SI↗

The stability of a graph partition: A dynamics-based framework for community detection

Recent years have seen a surge of interest in the analysis of complex networks, facilitated by the availability of relational data and the increasingly powerful computational resources that can be employed for their analysis. Naturally, the study of real-world systems leads to highly complex networks and a current challenge is to extract intelligible, simplified descriptions from the network in terms of relevant subgraphs, which can provide insight into the structure and function of the overall system. Sparked by seminal work by Newman and Girvan, an interesting line of research has been devoted to investigating modular community structure in networks, revitalising the classic problem of graph partitioning. However, modular or community structure in networks has notoriously evaded rigorous definition. The most accepted notion of community is perhaps that of a group of elements which exhibit a stronger level of interaction within themselves than with the elements outside the community. This concept has resulted in a plethora of computational methods and heuristics for community detection. Nevertheless a firm theoretical understanding of most of these methods, in terms of how they operate and what they are supposed to detect, is still lacking to date. Here, we will develop a dynamical perspective towards community detection enabling us to define a measure named the stability of a graph partition. It will be shown that a number of previously ad-hoc defined heuristics for community detection can be seen as particular cases of our method providing us with a dynamic reinterpretation of those measures. Our dynamics-based approach thus serves as a unifying framework to gain a deeper understanding of different aspects and problems associated with community detection and allows us to propose new dynamically-inspired criteria for community structure.

physics.soc-ph↗

On Periodic Reference Tracking Using Batch-Mode Reinforcement Learning with Application to Gene Regulatory Network Control

In this paper, we consider the periodic reference tracking problem in the framework of batch-mode reinforcement learning, which studies methods for solving optimal control problems from the sole knowledge of a set of trajectories. In particular, we extend an existing batch-mode reinforcement learning algorithm, known as Fitted Q Iteration, to the periodic reference tracking problem. The presented periodic reference tracking algorithm explicitly exploits a priori knowledge of the future values of the reference trajectory and its periodicity. We discuss the properties of our approach and illustrate it on the problem of reference tracking for a synthetic biology gene regulatory network known as the generalised repressilator. This system can produce decaying but long-lived oscillations, which makes it an interesting system for the tracking problem. In our companion paper we also take a look at the regulation problem of the toggle switch system, where the main goal is to drive the system's states to a specific bounded region in the state space.

eess.SY↗