109,695 research outputs found

    On the basic computational structure of gene regulatory networks

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    Gene regulatory networks constitute the first layer of the cellular computation for cell adaptation and surveillance. In these webs, a set of causal relations is built up from thousands of interactions between transcription factors and their target genes. The large size of these webs and their entangled nature make difficult to achieve a global view of their internal organisation. Here, this problem has been addressed through a comparative study for {\em Escherichia coli}, {\em Bacillus subtilis} and {\em Saccharomyces cerevisiae} gene regulatory networks. We extract the minimal core of causal relations, uncovering the hierarchical and modular organisation from a novel dynamical/causal perspective. Our results reveal a marked top-down hierarchy containing several small dynamical modules for \textit{E. coli} and \textit{B. subtilis}. Conversely, the yeast network displays a single but large dynamical module in the middle of a bow-tie structure. We found that these dynamical modules capture the relevant wiring among both common and organism-specific biological functions such as transcription initiation, metabolic control, signal transduction, response to stress, sporulation and cell cycle. Functional and topological results suggest that two fundamentally different forms of logic organisation may have evolved in bacteria and yeast.Comment: This article is published at Molecular Biosystems, Please cite as: Carlos Rodriguez-Caso, Bernat Corominas-Murtra and Ricard V. Sole. Mol. BioSyst., 2009, 5 pp 1617--171

    Feedbacks from the metabolic network to the genetic network reveal regulatory modules in E. coli and B. subtilis

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    The genetic regulatory network (GRN) plays a key role in controlling the response of the cell to changes in the environment. Although the structure of GRNs has been the subject of many studies, their large scale structure in the light of feedbacks from the metabolic network (MN) has received relatively little attention. Here we study the causal structure of the GRNs, namely the chain of influence of one component on the other, taking into account feedback from the MN. First we consider the GRNs of E. coli and B. subtilis without feedback from MN and illustrate their causal structure. Next we augment the GRNs with feedback from their respective MNs by including (a) links from genes coding for enzymes to metabolites produced or consumed in reactions catalyzed by those enzymes and (b) links from metabolites to genes coding for transcription factors whose transcriptional activity the metabolites alter by binding to them. We find that the inclusion of feedback from MN into GRN significantly affects its causal structure, in particular the number of levels and relative positions of nodes in the hierarchy, and the number and size of the strongly connected components (SCCs). We then study the functional significance of the SCCs. For this we identify condition specific feedbacks from the MN into the GRN by retaining only those enzymes that are essential for growth in specific environmental conditions simulated via the technique of flux balance analysis (FBA). We find that the SCCs of the GRN augmented by these feedbacks can be ascribed specific functional roles in the organism. Our algorithmic approach thus reveals relatively autonomous subsystems with specific functionality, or regulatory modules in the organism. This automated approach could be useful in identifying biologically relevant modules in other organisms for which network data is available, but whose biology is less well studied.Comment: 15 figure

    Recent progress on the notion of global hyperbolicity

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    Global hyperbolicity is a central concept in Mathematical Relativity. Here, we review the different approaches to this concept explaining both, classical approaches and recent results. The former includes Cauchy hypersurfaces, naked singularities, and the space of the causal curves connecting two events. The latter includes structural results on globally hyperbolic spacetimes, their embeddability in Lorentz-Minkowski, and the recently revised notions of both, causal and conformal boundaries. Moreover, two criteria for checking global hyperbolicity are reviewed. The first one applies to general splitting spacetimes. The second one characterizes accurately global hyperbolicity and spacelike Cauchy hypersurfaces for standard stationary spacetimes, in terms of a naturally associated Finsler metric.Comment: 18 pages, 1 figure. Extended and updated contribution to the meeting "New Developments in Lorentzian Geometry" Berlin, Nov. 200

    Graphical models for mediation analysis

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    Mediation analysis seeks to infer how much of the effect of an exposure on an outcome can be attributed to specific pathways via intermediate variables or mediators. This requires identification of so-called path-specific effects. These express how a change in exposure affects those intermediate variables (along certain pathways), and how the resulting changes in those variables in turn affect the outcome (along subsequent pathways). However, unlike identification of total effects, adjustment for confounding is insufficient for identification of path-specific effects because their magnitude is also determined by the extent to which individuals who experience large exposure effects on the mediator, tend to experience relatively small or large mediator effects on the outcome. This chapter therefore provides an accessible review of identification strategies under general nonparametric structural equation models (with possibly unmeasured variables), which rule out certain such dependencies. In particular, it is shown which path-specific effects can be identified under such models, and how this can be done

    Bridging the gap between general probabilistic theories and the device-independent framework for nonlocality and contextuality

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    Characterizing quantum correlations in terms of information-theoretic principles is a popular chapter of quantum foundations. Traditionally, the principles adopted for this scope have been expressed in terms of conditional probability distributions, specifying the probability that a black box produces a certain output upon receiving a certain input. This framework is known as "device-independent". Another major chapter of quantum foundations is the information-theoretic characterization of quantum theory, with its sets of states and measurements, and with its allowed dynamics. The different frameworks adopted for this scope are known under the umbrella term "general probabilistic theories". With only a few exceptions, the two programmes on characterizing quantum correlations and characterizing quantum theory have so far proceeded on separate tracks, each one developing its own methods and its own agenda. This paper aims at bridging the gap, by comparing the two frameworks and illustrating how the two programmes can benefit each other.Comment: 61 pages, no figures, published versio

    Causal structures and causal boundaries

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    We give an up-to-date perspective with a general overview of the theory of causal properties, the derived causal structures, their classification and applications, and the definition and construction of causal boundaries and of causal symmetries, mostly for Lorentzian manifolds but also in more abstract settings.Comment: Final version. To appear in Classical and Quantum Gravit
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