4,262 research outputs found

    LTRo: Learning to Route Queries in Clustered P2P IR

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    Query Routing is a critical step in P2P Information Retrieval. In this paper, we consider learning to rank approaches for query routing in the clustered P2P IR architecture. Our formulation, LTRo, scores resources based on the number of relevant documents for each training query, and uses that information to build a model that would then rank promising peers for a new query. Our empirical analysis over a variety of P2P IR testbeds illustrate the superiority of our method against the state-of-the-art methods for query routing

    The identification of informative genes from multiple datasets with increasing complexity

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    Background In microarray data analysis, factors such as data quality, biological variation, and the increasingly multi-layered nature of more complex biological systems complicates the modelling of regulatory networks that can represent and capture the interactions among genes. We believe that the use of multiple datasets derived from related biological systems leads to more robust models. Therefore, we developed a novel framework for modelling regulatory networks that involves training and evaluation on independent datasets. Our approach includes the following steps: (1) ordering the datasets based on their level of noise and informativeness; (2) selection of a Bayesian classifier with an appropriate level of complexity by evaluation of predictive performance on independent data sets; (3) comparing the different gene selections and the influence of increasing the model complexity; (4) functional analysis of the informative genes. Results In this paper, we identify the most appropriate model complexity using cross-validation and independent test set validation for predicting gene expression in three published datasets related to myogenesis and muscle differentiation. Furthermore, we demonstrate that models trained on simpler datasets can be used to identify interactions among genes and select the most informative. We also show that these models can explain the myogenesis-related genes (genes of interest) significantly better than others (P < 0.004) since the improvement in their rankings is much more pronounced. Finally, after further evaluating our results on synthetic datasets, we show that our approach outperforms a concordance method by Lai et al. in identifying informative genes from multiple datasets with increasing complexity whilst additionally modelling the interaction between genes. Conclusions We show that Bayesian networks derived from simpler controlled systems have better performance than those trained on datasets from more complex biological systems. Further, we present that highly predictive and consistent genes, from the pool of differentially expressed genes, across independent datasets are more likely to be fundamentally involved in the biological process under study. We conclude that networks trained on simpler controlled systems, such as in vitro experiments, can be used to model and capture interactions among genes in more complex datasets, such as in vivo experiments, where these interactions would otherwise be concealed by a multitude of other ongoing events

    A biophysical model of cell adhesion mediated by immunoadhesin drugs and antibodies

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    A promising direction in drug development is to exploit the ability of natural killer cells to kill antibody-labeled target cells. Monoclonal antibodies and drugs designed to elicit this effect typically bind cell-surface epitopes that are overexpressed on target cells but also present on other cells. Thus it is important to understand adhesion of cells by antibodies and similar molecules. We present an equilibrium model of such adhesion, incorporating heterogeneity in target cell epitope density and epitope immobility. We compare with experiments on the adhesion of Jurkat T cells to bilayers containing the relevant natural killer cell receptor, with adhesion mediated by the drug alefacept. We show that a model in which all target cell epitopes are mobile and available is inconsistent with the data, suggesting that more complex mechanisms are at work. We hypothesize that the immobile epitope fraction may change with cell adhesion, and we find that such a model is more consistent with the data. We also quantitatively describe the parameter space in which binding occurs. Our results point toward mechanisms relating epitope immobility to cell adhesion and offer insight into the activity of an important class of drugs.Comment: 13 pages, 5 figure

    Ordinary Percolation with Discontinuous Transitions

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    Percolation on a one-dimensional lattice and fractals such as the Sierpinski gasket is typically considered to be trivial because they percolate only at full bond density. By dressing up such lattices with small-world bonds, a novel percolation transition with explosive cluster growth can emerge at a nontrivial critical point. There, the usual order parameter, describing the probability of any node to be part of the largest cluster, jumps instantly to a finite value. Here, we provide a simple example of this transition in form of a small-world network consisting of a one-dimensional lattice combined with a hierarchy of long-range bonds that reveals many features of the transition in a mathematically rigorous manner.Comment: RevTex, 5 pages, 4 eps-figs, and Mathematica Notebook as Supplement included. Final version, with several corrections and improvements. For related work, see http://www.physics.emory.edu/faculty/boettcher

    BRCA1 and BRCA2 mutations in a population-based study of male breast cancer

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    Background: The contribution of BRCA1 and BRCA2 to the incidence of male breast cancer (MBC) in the United Kingdom is not known, and the importance of these genes in the increased risk of female breast cancer associated with a family history of breast cancer in a male first-degree relative is unclear. Methods: We have carried out a population-based study of 94 MBC cases collected in the UK. We screened genomic DNA for mutations in BRCA1 and BRCA2 and used family history data from these cases to calculate the risk of breast cancer to female relatives of MBC cases. We also estimated the contribution of BRCA1 and BRCA2 to this risk. Results: Nineteen cases (20%) reported a first-degree relative with breast cancer, of whom seven also had an affected second-degree relative. The breast cancer risk in female first-degree relatives was 2.4 times (95% confidence interval [CI] = 1.4–4.0) the risk in the general population. No BRCA1 mutation carriers were identified and five cases were found to carry a mutation in BRCA2. Allowing for a mutation detection sensitivity frequency of 70%, the carrier frequency for BRCA2 mutations was 8% (95% CI = 3–19). All the mutation carriers had a family history of breast, ovarian, prostate or pancreatic cancer. However, BRCA2 accounted for only 15% of the excess familial risk of breast cancer in female first-degree relatives. Conclusion: These data suggest that other genes that confer an increased risk for both female and male breast cancer have yet to be found

    Kerr-AdS and its Near-horizon Geometry: Perturbations and the Kerr/CFT Correspondence

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    We investigate linear perturbations of spin-s fields in the Kerr-AdS black hole and in its near-horizon geometry (NHEK-AdS), using the Teukolsky master equation and the Hertz potential. In the NHEK-AdS geometry we solve the associated angular equation numerically and the radial equation exactly. Having these explicit solutions at hand, we search for linear mode instabilities. We do not find any (non-)axisymmetric instabilities with outgoing boundary conditions. This is in agreement with a recent conjecture relating the linearized stability properties of the full geometry with those of its near-horizon geometry. Moreover, we find that the asymptotic behaviour of the metric perturbations in NHEK-AdS violates the fall-off conditions imposed in the formulation of the Kerr/CFT correspondence (the only exception being the axisymmetric sector of perturbations).Comment: 26 pages. 4 figures. v2: references added. matches published versio

    Discovering study-specific gene regulatory networks

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    This article has been made available through the Brunel Open Access Publishing Fund.Microarrays are commonly used in biology because of their ability to simultaneously measure thousands of genes under different conditions. Due to their structure, typically containing a high amount of variables but far fewer samples, scalable network analysis techniques are often employed. In particular, consensus approaches have been recently used that combine multiple microarray studies in order to find networks that are more robust. The purpose of this paper, however, is to combine multiple microarray studies to automatically identify subnetworks that are distinctive to specific experimental conditions rather than common to them all. To better understand key regulatory mechanisms and how they change under different conditions, we derive unique networks from multiple independent networks built using glasso which goes beyond standard correlations. This involves calculating cluster prediction accuracies to detect the most predictive genes for a specific set of conditions. We differentiate between accuracies calculated using cross-validation within a selected cluster of studies (the intra prediction accuracy) and those calculated on a set of independent studies belonging to different study clusters (inter prediction accuracy). Finally, we compare our method's results to related state-of-the art techniques. We explore how the proposed pipeline performs on both synthetic data and real data (wheat and Fusarium). Our results show that subnetworks can be identified reliably that are specific to subsets of studies and that these networks reflect key mechanisms that are fundamental to the experimental conditions in each of those subsets
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