198 research outputs found

    A ratiometric-based measure of gene co-expression

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    Background: Gene co-expression analysis has previously been based on measures that include correlation coefficients and mutual information, as well as newcomers such as MIC. These measures depend primarily on the degree of association between the RNA levels of two genes and to a lesser extent on their variability. They focus on the similarity of expression value trajectories that change in like manner across samples. However there are relationships of biological interest for which these classical measures are expected to be insensitive. These include genes whose expression levels are ratiometrically stable and genes whose variance is tightly constrained. Large-scale studies of relatively homogeneous samples, including single cell RNA-seq, are experimental settings in which such relationships might be especially pertinent. Results: We develop and implement a ratiometric approach for detecting gene associations (abbreviated RA). It is based on the coefficient of variation of the measured expression ratio of each pair of genes. We apply it to a collection of lymphoblastoid RNA-seq data from the 1000 Genomes Project Consortium, a typical sample set with high overall homogeneity. RA is a selective method, reporting in this case ~1/4 of all possible gene pairs, yet these relationships include a distilled picture of biological relationships previously found by other methods. In addition, RA reveals expression relationships that are not detected by traditional correlation and mutual information methods. We also analyze data from individual lymphoblastoid cells and show that desirable properties of the RA method extend to single-cell RNA-seq. Conclusion: We show that our ratiometric method identifies biologically significant relationships that are often missed or low-ranked by conventional association-based methods when applied to a relatively homogenous dataset. The results open new questions about the regulatory mechanisms that produce strong RA relationships. RA is scalable and potentially well suited for the analysis of thousands of bulk-RNA or single-cell transcriptomes

    Mapping a multiplexed zoo of mRNA expression

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    In situ hybridization methods are used across the biological sciences to map mRNA expression within intact specimens. Multiplexed experiments, in which multiple target mRNAs are mapped in a single sample, are essential for studying regulatory interactions, but remain cumbersome in most model organisms. Programmable in situ amplifiers based on the mechanism of hybridization chain reaction (HCR) overcome this longstanding challenge by operating independently within a sample, enabling multiplexed experiments to be performed with an experimental timeline independent of the number of target mRNAs. To assist biologists working across a broad spectrum of organisms, we demonstrate multiplexed in situ HCR in diverse imaging settings: bacteria, whole-mount nematode larvae, whole-mount fruit fly embryos, whole-mount sea urchin embryos, whole-mount zebrafish larvae, whole-mount chicken embryos, whole-mount mouse embryos and formalin-fixed paraffin-embedded human tissue sections. In addition to straightforward multiplexing, in situ HCR enables deep sample penetration, high contrast and subcellular resolution, providing an incisive tool for the study of interlaced and overlapping expression patterns, with implications for research communities across the biological sciences

    Common ground in collaborative intelligence analysis: an empirical study

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    This paper reports an empirical exploration of how different configurations of collaboration technology affect peoples’ ability to construct and maintain common ground while conducting collaborative intelligence analysis work. Prior studies of collaboration technology have typically focused on simpler conversational tasks, or ones that involve physical manipulation, rather than the complex sensemaking and inference involved in intelligence work. The study explores the effects of video communication and shared visual workspace (SVW) on the negotiation of common ground by distributed teams collaborating in real time on intelligence analysis tasks. The experimental study uses a 2x2 factorial, between-subjects design involving two independent variables: presence or absence of Video and SVW. Two-member teams were randomly assigned to one of the four experimental media conditions and worked to complete several intelligence analysis tasks involving multiple, complex intelligence artefacts. Teams with access to the shared visual workspace could view their teammates’ eWhiteboards. Our results demonstrate a significant effect for the shared visual workspace: the effort of conversational grounding is reduced in the cases where SVW is available. However, there were no main effects for video and no interaction between the two variables. Also, we found that the “conversational grounding effort” required tended to decrease over the course of the tas

    Mitigating effects of vaccination on influenza outbreaks given constraints in stockpile size and daily administration capacity

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    <p>Abstract</p> <p>Background</p> <p>Influenza viruses are a major cause of morbidity and mortality worldwide. Vaccination remains a powerful tool for preventing or mitigating influenza outbreaks. Yet, vaccine supplies and daily administration capacities are limited, even in developed countries. Understanding how such constraints can alter the mitigating effects of vaccination is a crucial part of influenza preparedness plans. Mathematical models provide tools for government and medical officials to assess the impact of different vaccination strategies and plan accordingly. However, many existing models of vaccination employ several questionable assumptions, including a rate of vaccination <it>proportional </it>to the population at each point in time.</p> <p>Methods</p> <p>We present a SIR-like model that explicitly takes into account vaccine supply and the <it>number </it>of vaccines administered per day and places data-informed limits on these parameters. We refer to this as the <it>non-proportional </it>model of vaccination and compare it to the proportional scheme typically found in the literature.</p> <p>Results</p> <p>The proportional and non-proportional models behave similarly for a few different vaccination scenarios. However, there are parameter regimes involving the vaccination campaign duration and daily supply limit for which the non-proportional model predicts smaller epidemics that peak later, but may last longer, than those of the proportional model. We also use the non-proportional model to predict the mitigating effects of variably timed vaccination campaigns for different levels of vaccination coverage, using specific constraints on daily administration capacity.</p> <p>Conclusions</p> <p>The non-proportional model of vaccination is a theoretical improvement that provides more accurate predictions of the mitigating effects of vaccination on influenza outbreaks than the proportional model. In addition, parameters such as vaccine supply and daily administration limit can be easily adjusted to simulate conditions in developed and developing nations with a wide variety of financial and medical resources. Finally, the model can be used by government and medical officials to create customized pandemic preparedness plans based on the supply and administration constraints of specific communities.</p

    Die Stoffwechselwirkungen der SchilddrĂŒsenhormone

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    Mapping a multiplexed zoo of mRNA expression

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    In situ hybridization methods are used across the biological sciences to map mRNA expression within intact specimens. Multiplexed experiments, in which multiple target mRNAs are mapped in a single sample, are essential for studying regulatory interactions, but remain cumbersome in most model organisms. Programmable in situ amplifiers based on the mechanism of hybridization chain reaction (HCR) overcome this longstanding challenge by operating independently within a sample, enabling multiplexed experiments to be performed with an experimental timeline independent of the number of target mRNAs. To assist biologists working across a broad spectrum of organisms, we demonstrate multiplexed in situ HCR in diverse imaging settings: bacteria, whole-mount nematode larvae, whole-mount fruit fly embryos, whole-mount sea urchin embryos, whole-mount zebrafish larvae, whole-mount chicken embryos, whole-mount mouse embryos and formalin-fixed paraffin-embedded human tissue sections. In addition to straightforward multiplexing, in situ HCR enables deep sample penetration, high contrast and subcellular resolution, providing an incisive tool for the study of interlaced and overlapping expression patterns, with implications for research communities across the biological sciences
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