276 research outputs found

    Beyond element-wise interactions: identifying complex interactions in biological processes

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    Background: Biological processes typically involve the interactions of a number of elements (genes, cells) acting on each others. Such processes are often modelled as networks whose nodes are the elements in question and edges pairwise relations between them (transcription, inhibition). But more often than not, elements actually work cooperatively or competitively to achieve a task. Or an element can act on the interaction between two others, as in the case of an enzyme controlling a reaction rate. We call “complex” these types of interaction and propose ways to identify them from time-series observations. Methodology: We use Granger Causality, a measure of the interaction between two signals, to characterize the influence of an enzyme on a reaction rate. We extend its traditional formulation to the case of multi-dimensional signals in order to capture group interactions, and not only element interactions. Our method is extensively tested on simulated data and applied to three biological datasets: microarray data of the Saccharomyces cerevisiae yeast, local field potential recordings of two brain areas and a metabolic reaction. Conclusions: Our results demonstrate that complex Granger causality can reveal new types of relation between signals and is particularly suited to biological data. Our approach raises some fundamental issues of the systems biology approach since finding all complex causalities (interactions) is an NP hard problem

    Climate change, water management and stakeholder analysis in the Dongjiang River basin in South China

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    This article proposes a systematic analysis of water management and allocation on the scale of a river basin, considering climate impacts and stakeholder networks in the Dongjiang River basin in South China. Specific approaches are integrated to explore various subtopics. Findings indicate a slight increase of precipitation in the basin and strong fluctuations in this century due to climate extremes, which may lead to seasonal or quality-related water shortages. It is highlighted that alternative options for holistic water management are needed in the basin, and participatory water allocation mechanisms and establishment of a basin-wide management framework could be helpful

    Simpson's Paradox, Lord's Paradox, and Suppression Effects are the same phenomenon – the reversal paradox

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    This article discusses three statistical paradoxes that pervade epidemiological research: Simpson's paradox, Lord's paradox, and suppression. These paradoxes have important implications for the interpretation of evidence from observational studies. This article uses hypothetical scenarios to illustrate how the three paradoxes are different manifestations of one phenomenon – the reversal paradox – depending on whether the outcome and explanatory variables are categorical, continuous or a combination of both; this renders the issues and remedies for any one to be similar for all three. Although the three statistical paradoxes occur in different types of variables, they share the same characteristic: the association between two variables can be reversed, diminished, or enhanced when another variable is statistically controlled for. Understanding the concepts and theory behind these paradoxes provides insights into some controversial or contradictory research findings. These paradoxes show that prior knowledge and underlying causal theory play an important role in the statistical modelling of epidemiological data, where incorrect use of statistical models might produce consistent, replicable, yet erroneous results

    Strong Pinning in High Temperature Superconductors

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    Detailed measurements of the critical current density jc of YBa2Cu3O7 films grown by pulsed laser deposition reveal the increase of jc as function of the filmthickness. Both this thickness dependence and the field dependence of the critical current are consistently described using a generalization of the theory of strong pinning of Ovchinnikov and Ivlev [Phys. Rev. B 43, 8024 (1991)]. From the model, we deduce values of the defect density (10^21 m^-3) and the elementary pinning force, which are in good agreement with the generally accepted values for Y2O3-inclusions. In the absence of clear evidence that the critical current is determined by linear defects or modulations of the film thickness, our model provides an alternative explanation for the rather universal field dependence of the critical current density found in YBa2Cu3O7 films deposited by different methods.Comment: 11 pages; 8 Figures; Published Phys. Rev. B 66, 024523 (2002

    Theory of Type-II Superconductors with Finite London Penetration Depth

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    Previous continuum theory of type-II superconductors of various shapes with and without vortex pinning in an applied magnetic field and with transport current, is generalized to account for a finite London penetration depth lambda. This extension is particularly important at low inductions B, where the transition to the Meissner state is now described correctly, and for films with thickness comparable to or smaller than lambda. The finite width of the surface layer with screening currents and the correct dc and ac responses in various geometries follow naturally from an equation of motion for the current density in which the integral kernel now accounts for finite lambda. New geometries considered here are thick and thin strips with applied current, and `washers', i.e. thin film squares with a slot and central hole as used for SQUIDs.Comment: 14 pages, including 15 high-resolution figure

    A study on decision-making of food supply chain based on big data

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    As more and more companies have captured and analyzed huge volumes of data to improve the performance of supply chain, this paper develops a big data harvest model that uses big data as inputs to make more informed production decisions in the food supply chain. By introducing a method of Bayesian network, this paper integrates sample data and finds a cause-and-effect between data to predict market demand. Then the deduction graph model that translates products demand into processes and divides processes into tasks and assets is presented, and an example of how big data in the food supply chain can be combined with Bayesian network and deduction graph model to guide production decision. Our conclusions indicate that the analytical framework has vast potential for supporting support decision making by extracting value from big data

    Deterministic Effects Propagation Networks for reconstructing protein signaling networks from multiple interventions

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    <p>Abstract</p> <p>Background</p> <p>Modern gene perturbation techniques, like RNA interference (RNAi), enable us to study effects of targeted interventions in cells efficiently. In combination with mRNA or protein expression data this allows to gain insights into the behavior of complex biological systems.</p> <p>Results</p> <p>In this paper, we propose Deterministic Effects Propagation Networks (DEPNs) as a special Bayesian Network approach to reverse engineer signaling networks from a combination of protein expression and perturbation data. DEPNs allow to reconstruct protein networks based on combinatorial intervention effects, which are monitored via changes of the protein expression or activation over one or a few time points. Our implementation of DEPNs allows for latent network nodes (i.e. proteins without measurements) and has a built in mechanism to impute missing data. The robustness of our approach was tested on simulated data. We applied DEPNs to reconstruct the <it>ERBB </it>signaling network in <it>de novo </it>trastuzumab resistant human breast cancer cells, where protein expression was monitored on Reverse Phase Protein Arrays (RPPAs) after knockdown of network proteins using RNAi.</p> <p>Conclusion</p> <p>DEPNs offer a robust, efficient and simple approach to infer protein signaling networks from multiple interventions. The method as well as the data have been made part of the latest version of the R package "nem" available as a supplement to this paper and via the Bioconductor repository.</p

    Hierarchical coordination of periodic genes in the cell cycle of Saccharomyces cerevisiae

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    <p>Abstract</p> <p>Background</p> <p>Gene networks are a representation of molecular interactions among genes or products thereof and, hence, are forming causal networks. Despite intense studies during the last years most investigations focus so far on inferential methods to reconstruct gene networks from experimental data or on their structural properties, e.g., degree distributions. Their structural analysis to gain functional insights into organizational principles of, e.g., pathways remains so far under appreciated.</p> <p>Results</p> <p>In the present paper we analyze cell cycle regulated genes in <it>S. cerevisiae</it>. Our analysis is based on the transcriptional regulatory network, representing causal interactions and not just associations or correlations between genes, and a list of known periodic genes. No further data are used. Partitioning the transcriptional regulatory network according to a graph theoretical property leads to a hierarchy in the network and, hence, in the information flow allowing to identify two groups of periodic genes. This reveals a novel conceptual interpretation of the working mechanism of the cell cycle and the genes regulated by this pathway.</p> <p>Conclusion</p> <p>Aside from the obtained results for the cell cycle of yeast our approach could be exemplary for the analysis of general pathways by exploiting the rich causal structure of inferred and/or curated gene networks including protein or signaling networks.</p
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