Estimating the epidemic risk using non-uniformly sampled contact data

Many datasets describing contacts in a population suffer from incompleteness due to population sampling and underreporting of contacts. Data-driven simulations of spreading processes using such incomplete data lead to an underestimation of the epidemic risk, and it is therefore important to devise methods to correct this bias. We focus here on a non-uniform sampling of the contacts between individuals, aimed at mimicking the results of diaries or surveys, and consider as case studies two datasets collected in different contexts. We show that using surrogate data built using a method developed in the case of uniform population sampling yields an improvement with respect to the use of the sampled data but is strongly limited by the underestimation of the link density in the sampled network. We put forward a second method to build surrogate data that assumes knowledge of the density of links within one of the groups forming the population. We show that it gives very good results when the population is strongly structured, and discuss its limitations in the case of a population with a weaker group structure. These limitations highlight the interest of measurements using wearable sensors able to yield accurate information on the structure and durations of contacts

Uncovering distinct protein-network topologies in heterogeneous cell populations

Background: Cell biology research is fundamentally limited by the number of intracellular components, particularly proteins, that can be co-measured in the same cell. Therefore, cell-to-cell heterogeneity in unmeasured proteins can lead to completely different observed relations between the same measured proteins. Attempts to infer such relations in a heterogeneous cell population can yield uninformative average relations if only one underlying biochemical network is assumed. To address this, we developed a method that recursively couples an iterative unmixing process with a Bayesian analysis of each unmixed subpopulation. Results: Our approach enables to identify the number of distinct cell subpopulations, unmix their corresponding observations and resolve the network structure of each subpopulation. Using simulations of the MAPK pathway upon EGF and NGF stimulations we assess the performance of the method. We demonstrate that the presented method can identify better than clustering approaches the number of subpopulations within a mixture of observations, thus resolving correctly the statistical relations between the proteins. Conclusions: Coupling the unmixing of multiplexed observations with the inference of statistical relations between the measured parameters is essential for the success of both of these processes. Here we present a conceptual and algorithmic solution to achieve such coupling and hence to analyze data obtained from a natural mixture of cell populations. As the technologies and necessity for multiplexed measurements are rising in the systems biology era, this work addresses an important current challenge in the analysis of the derived data.Fil: Wieczorek, Jakob. Universitat Dortmund; AlemaniaFil: Malik Sheriff, Rahuman S.. Institut Max Planck fur Molekulare Physiologie; Alemania. Imperial College London; Reino Unido. European Bioinformatics Institute. European Molecular Biology Laboratory; Reino UnidoFil: Fermin, Yessica. Universitat Dortmund; AlemaniaFil: Grecco, Hernan Edgardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina. Institut Max Planck fur Molekulare Physiologie; AlemaniaFil: Zamir, Eli. Institut Max Planck fur Molekulare Physiologie; AlemaniaFil: Ickstadt, Katja. Universitat Dortmund; Alemani

Epidemic risk from friendship network data: an equivalence with a non-uniform sampling of contact networks

Contacts between individuals play an important role in determining how infectious diseases spread. Various methods to gather data on such contacts co-exist, from surveys to wearable sensors. Comparisons of data obtained by different methods in the same context are however scarce, in particular with respect to their use in data-driven models of spreading processes. Here, we use a combined data set describing contacts registered by sensors and friendship relations in the same population to address this issue in a case study. We investigate if the use of the friendship network is equivalent to a sampling procedure performed on the sensor contact network with respect to the outcome of simulations of spreading processes: such an equivalence might indeed give hints on ways to compensate for the incompleteness of contact data deduced from surveys. We show that this is indeed the case for these data, for a specifically designed sampling procedure, in which respondents report their neighbors with a probability depending on their contact time. We study the impact of this specific sampling procedure on several data sets, discuss limitations of our approach and its possible applications in the use of data sets of various origins in data-driven simulations of epidemic processes

Spectral convergence in tapping and physiological fluctuations: coupling and independence of 1/f noise in the central and autonomic nervous systems.

When humans perform a response task or timing task repeatedly, fluctuations in measures of timing from one action to the next exhibit long-range correlations known as 1/f noise. The origins of 1/f noise in timing have been debated for over 20 years, with one common explanation serving as a default: humans are composed of physiological processes throughout the brain and body that operate over a wide range of timescales, and these processes combine to be expressed as a general source of 1/f noise. To test this explanation, the present study investigated the coupling vs. independence of 1/f noise in timing deviations, key-press durations, pupil dilations, and heartbeat intervals while tapping to an audiovisual metronome. All four dependent measures exhibited clear 1/f noise, regardless of whether tapping was synchronized or syncopated. 1/f spectra for timing deviations were found to match those for key-press durations on an individual basis, and 1/f spectra for pupil dilations matched those in heartbeat intervals. Results indicate a complex, multiscale relationship among 1/f noises arising from common sources, such as those arising from timing functions vs. those arising from autonomic nervous system (ANS) functions. Results also provide further evidence against the default hypothesis that 1/f noise in human timing is just the additive combination of processes throughout the brain and body. Our findings are better accommodated by theories of complexity matching that begin to formalize multiscale coordination as a foundation of human behavior

Elasticity sampling links thermodynamics to metabolic control

Metabolic networks can be turned into kinetic models in a predefined steady state by sampling the reaction elasticities in this state. Elasticities for many reversible rate laws can be computed from the reaction Gibbs free energies, which are determined by the state, and from physically unconstrained saturation values. Starting from a network structure with allosteric regulation and consistent metabolic fluxes and concentrations, one can sample the elasticities, compute the control coefficients, and reconstruct a kinetic model with consistent reversible rate laws. Some of the model variables are manually chosen, fitted to data, or optimised, while the others are computed from them. The resulting model ensemble allows for probabilistic predictions, for instance, about possible dynamic behaviour. By adding more data or tighter constraints, the predictions can be made more precise. Model variants differing in network structure, flux distributions, thermodynamic forces, regulation, or rate laws can be realised by different model ensembles and compared by significance tests. The thermodynamic forces have specific effects on flux control, on the synergisms between enzymes, and on the emergence and propagation of metabolite fluctuations. Large kinetic models could help to simulate global metabolic dynamics and to predict the effects of enzyme inhibition, differential expression, genetic modifications, and their combinations on metabolic fluxes. MATLAB code for elasticity sampling is freely available