1,721,362 research outputs found
Applications et mécanismes de l’interférence ARN / RNA interference: Mechanisms and Applications
No full textColloque organisé par Tony Hyman et Norbert Perrimon du 23 au 28 juin 2004 Participants Julie Ahringer, Joe Bader, Buzz Baum, Michael Boutros, Anne E. Carpenter, Barry Dickson, Ulrike Eggert, Kris Gunsalus, Craig P. Hunter, Tony Hyman, Amy Kiger, John Kim, Joshua LaBaer, Stanley (Stan) Letovsky, Bernard Mathey-Prevot, Andrew P. McMahon, Craig Mello, Norbert Perrimon , Fabio Piano, Marc Vidal Résumé La découverte, au début des années 1990, que de petits ARN pouvaient inhiber l’expression de d..
Abstract IA11: Combinatorial screens in Drosophila cells
No full textAbstract
Our laboratory is combining a number of omics approaches (Mass Spec, RNAi, phosphoproteomics, and transcriptomics) to expand our understanding of the structure of signaling networks. Applying these approaches has allowed us to identify additional components of a number of signaling networks including the MAPK/ERK, AKT/PI3K, Hippo, Insulin and autophagy pathways (Friedman et al., 2011; Vinayagam et al., 2013; Neumüller et al., 2013; Kwon et al., 2013; Zirin et al., 2015; Vinayagam et al., 2016). An important finding from large-scale studies is that we could only functionally validate about half of the network components using single-gene loss of function studies, suggesting a high level of functional redundancy within network. For example, using Mass Spec we generated an Insulin pathway interactome of about 560 proteins and only 50% were found to affect pathway output as measured using phospho-specific antibodies (Vinayagam et al., 2016). To interrogate redundancy, we established a robust platform for performing combinatorial screens and used it to identify synthetic lethal (SL) interactions with a number of tumor suppressors such as TSC1 and TSC2 (Housden et al., 2015). Importantly, almost all the SL interactions we discovered in the fly screens turned out to be conserved in mammalian cells (collaboration with Alex Valvezan and Brendan Manning). These studies have led to identification of promising drug targets, and, as some of these are known targets of FDA approved drugs, drug candidates.
To expand SL screens in Drosophila cells, we have developed two new powerful screening approaches: 1. Pooled CRISPR and CRISPRa screens, and 2. Variable Dose Analysis, a screening method that exhibits significant reduced noise compared to previous SL screening methods. These approaches allow us to not only identify evolutionary conserved SL interactions that can lead to promising drug targets, but also to build a network of SL interactions that we will be able to compare to yeast SL network in particular. Results from these studies will provide fundamental information on the extent of conservation of SL across organisms, an issue that has not been addressed rigorously yet.
References
Friedman AA, Tucker G, Singh R, Yan D, Vinayagam A, Hu Y, Binari R, Hong P, Sun X, Porto M, Pacifico S, Murali T, Finley RL Jr, Asara JM, Berger B, Perrimon N. Proteomic and functional genomic landscape of receptor tyrosine kinase and ras to extracellular signal-regulated kinase signaling. Sci Signal. 2011 Oct 25;4(196):rs10. PMID: 22028469.
Vinayagam A, Hu Y, Kulkarni M, Roesel C, Sopko R, Mohr SE, Perrimon N. Protein complex-based analysis framework for high-throughput data sets. Sci Signal. 2013 Feb 26;6(264):rs5. PMID: 23443684.
Neumüller RA, Gross T, Samsonova AA, Vinayagam A, Buckner M, Founk K, Hu Y, Sharifpoor S, Rosebrock AP, Andrews B, Winston F, Perrimon N. Conserved regulators of nucleolar size revealed by global phenotypic analyses. Sci Signal. 2013 Aug 20;6(289):ra70. PMID: 23962978.
Kwon Y, Vinayagam A, Sun X, Dephoure N, Gygi SP, Hong P, Perrimon N. The Hippo signaling pathway interactome. Science. 2013 Nov 8;342(6159):737-40. PMID: 24114784.
Zirin J, Nieuwenhuis J, Samsonova A, Tao R, Perrimon N. Regulators of autophagosome formation in Drosophila muscles. PLoS Genet. 2015 Feb 18;11(2):e1005006. PMID: 25692684.
Housden BE, Valvezan AJ, Kelley C, Sopko R, Hu Y, Roesel C, Lin S, Buckner M, Tao R, Yilmazel B, Mohr SE, Manning BD, Perrimon N. Identification of potential drug targets for tuberous sclerosis complex by synthetic screens combining CRISPR-based knockouts with RNAi. Sci Signal. 2015 Sep 8;8(393):rs9. PMID: 26350902.
Vinayagam A, Kulkarni MM, Sopko R, Sun X, Hu Y, Nand A, Villalta C, Moghimi A, Yang X, Mohr SE, Hong P, Asara JM, Perrimon N. An Integrative Analysis of the InR/PI3K/Akt Network Identifies the Dynamic Response to Insulin Signaling. Cell Rep. 2016 Sep 13;16(11):3062-74. PMID: 27626673.
Citation Format: Norbert Perrimon. Combinatorial screens in Drosophila cells [abstract]. In: Proceedings of the AACR Precision Medicine Series: Opportunities and Challenges of Exploiting Synthetic Lethality in Cancer; Jan 4-7, 2017; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2017;16(10 Suppl):Abstract nr IA11.</jats:p
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Structure et dynamique des réseaux de régulation cellulaire / Structure and Dynamics of Cellular Regulatory Networks
No full textColloque organisé par Albert Goldbeter (Université Libre de Bruxelles) et Marc Vidal (Harvard University) du 6 au 11 juin 2011 Participants Bertrand Benazeraf, François-Yves Bouget, Jacques Demongeot, Claude Gérard, Albert Goldbeter, Thomas Höfer, Marcelline Kaufman, Steve A. Kay, Patrick Lemaire, Alfonso Martinez Arias, Vidyanand Nanjundiah, Bela Novak, Norbert Perrimon, David Rand, Nicolas Simonis, Denis Thieffry, John J. Tyson, Jacques van Helden, Michael White -- Résumé Systems Biology de..
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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