858 research outputs found

    Global alignment of protein-protein interaction networks by graph matching methods

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    Aligning protein-protein interaction (PPI) networks of different species has drawn a considerable interest recently. This problem is important to investigate evolutionary conserved pathways or protein complexes across species, and to help in the identification of functional orthologs through the detection of conserved interactions. It is however a difficult combinatorial problem, for which only heuristic methods have been proposed so far. We reformulate the PPI alignment as a graph matching problem, and investigate how state-of-the-art graph matching algorithms can be used for that purpose. We differentiate between two alignment problems, depending on whether strict constraints on protein matches are given, based on sequence similarity, or whether the goal is instead to find an optimal compromise between sequence similarity and interaction conservation in the alignment. We propose new methods for both cases, and assess their performance on the alignment of the yeast and fly PPI networks. The new methods consistently outperform state-of-the-art algorithms, retrieving in particular 78% more conserved interactions than IsoRank for a given level of sequence similarity. Availability:http://cbio.ensmp.fr/proj/graphm\_ppi/, additional data and codes are available upon request. Contact: [email protected]: Preprint versio

    Contribution of HEP electronics techniques to the medical imaging field

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    présenté par P.-E. Vert, proceedings sous forme de CD Imagerie Médical

    Outdoor blue spaces, human health and well-being: A systematic review of quantitative studies

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    This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordBACKGROUND: A growing number of quantitative studies have investigated the potential benefits of outdoor blue spaces (lakes, rivers, sea, etc) and human health, but there is not yet a systematic review synthesizing this evidence. OBJECTIVES: To systematically review the current quantitative evidence on human health and well-being benefits of outdoor blue spaces. METHODS: Following PRISMA guidelines for reporting systematic reviews and meta-analysis, observational and experimental quantitative studies focusing on both residential and non-residential outdoor blue space exposure were searched using specific keywords. RESULTS: In total 35 studies were included in the current systematic review, most of them being classified as of "good quality" (N=22). The balance of evidence suggested a positive association between greater exposure to outdoor blue spaces and both benefits to mental health and well-being (N=12 studies) and levels of physical activity (N=13 studies). The evidence of an association between outdoor blue space exposure and general health (N=6 studies), obesity (N=8 studies) and cardiovascular (N=4 studies) and related outcomes was less consistent. CONCLUSIONS: Although encouraging, there remains relatively few studies and a large degree of heterogeneity in terms of study design, exposure metrics and outcome measures, making synthesis difficult. Further research is needed using longitudinal research and natural experiments, preferably across a broader range of countries, to better understand the causal associations between blue spaces, health and wellbeing.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 666773

    Dual role for ubiquitin in plant steroid hormone receptor endocytosis

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    Brassinosteroids are plant steroid hormones that control many aspects of plant growth and development, and are perceived at the cell surface by the plasma membrane-localized receptor kinase BRI1. Here we show that BRI1 is post-translationally modified by K63 polyubiquitin chains in vivo. Using both artificial ubiquitination of BRI1 and generation of an ubiquitination-defective BRI1 mutant form, we demonstrate that ubiquitination promotes BRI1 internalization from the cell surface and is essential for its recognition at the trans-Golgi network/early endosomes (TGN/EE) for vacuolar targeting. Finally, we demonstrate that the control of BRI1 protein dynamics by ubiquitination is an important control mechanism for brassinosteroid responses in plants. Altogether, our results identify ubiquitination and K63-linked polyubiquitin chain formation as a dual targeting signal for BRI1 internalization and sorting along the endocytic pathway, and highlight its role in hormonally controlled plant development

    The influence of feature selection methods on accuracy, stability and interpretability of molecular signatures

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    Motivation: Biomarker discovery from high-dimensional data is a crucial problem with enormous applications in biology and medicine. It is also extremely challenging from a statistical viewpoint, but surprisingly few studies have investigated the relative strengths and weaknesses of the plethora of existing feature selection methods. Methods: We compare 32 feature selection methods on 4 public gene expression datasets for breast cancer prognosis, in terms of predictive performance, stability and functional interpretability of the signatures they produce. Results: We observe that the feature selection method has a significant influence on the accuracy, stability and interpretability of signatures. Simple filter methods generally outperform more complex embedded or wrapper methods, and ensemble feature selection has generally no positive effect. Overall a simple Student's t-test seems to provide the best results. Availability: Code and data are publicly available at http://cbio.ensmp.fr/~ahaury/

    Modeling recursive RNA interference.

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    An important application of the RNA interference (RNAi) pathway is its use as a small RNA-based regulatory system commonly exploited to suppress expression of target genes to test their function in vivo. In several published experiments, RNAi has been used to inactivate components of the RNAi pathway itself, a procedure termed recursive RNAi in this report. The theoretical basis of recursive RNAi is unclear since the procedure could potentially be self-defeating, and in practice the effectiveness of recursive RNAi in published experiments is highly variable. A mathematical model for recursive RNAi was developed and used to investigate the range of conditions under which the procedure should be effective. The model predicts that the effectiveness of recursive RNAi is strongly dependent on the efficacy of RNAi at knocking down target gene expression. This efficacy is known to vary highly between different cell types, and comparison of the model predictions to published experimental data suggests that variation in RNAi efficacy may be the main cause of discrepancies between published recursive RNAi experiments in different organisms. The model suggests potential ways to optimize the effectiveness of recursive RNAi both for screening of RNAi components as well as for improved temporal control of gene expression in switch off-switch on experiments

    Multi-Target Prediction: A Unifying View on Problems and Methods

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    Multi-target prediction (MTP) is concerned with the simultaneous prediction of multiple target variables of diverse type. Due to its enormous application potential, it has developed into an active and rapidly expanding research field that combines several subfields of machine learning, including multivariate regression, multi-label classification, multi-task learning, dyadic prediction, zero-shot learning, network inference, and matrix completion. In this paper, we present a unifying view on MTP problems and methods. First, we formally discuss commonalities and differences between existing MTP problems. To this end, we introduce a general framework that covers the above subfields as special cases. As a second contribution, we provide a structured overview of MTP methods. This is accomplished by identifying a number of key properties, which distinguish such methods and determine their suitability for different types of problems. Finally, we also discuss a few challenges for future research
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