1,721,015 research outputs found
NetworKIN: a resource for exploring cellular phosphorylation networks
Get PDFProtein kinases control cellular responses by phosphorylating specific substrates. Recent proteome-wide mapping of protein phosphorylation sites by mass spectrometry has discovered thousands of in vivo sites. Systematically assigning all 518 human kinases to all these sites is a challenging problem. The NetworKIN database (http://networkin.info) integrates consensus substrate motifs with context modelling for improved prediction of cellular kinase–substrate relations. Based on the latest human phosphoproteome from the Phospho.ELM and PhosphoSite databases, the resource offers insight into phosphorylation-modulated interaction networks. Here, we describe how NetworKIN can be used for both global and targeted molecular studies. Via the web interface users can query the database of precomputed kinase–substrate relations or obtain predictions on novel phosphoproteins. The database currently contains a predicted phosphorylation network with 20 224 site-specific interactions involving 3978 phosphoproteins and 73 human kinases from 20 families.Genome Canada (through Ontario Genomics Institute)National Institutes of Health (U.S.) (U54-CA112967)National Institutes of Health (U.S.) (GM60594)European Community’s Human Potential Programme (BioSapiens Network of Excellence (contract number LSHG-CT-2003-503265))European Community’s Human Potential Programme (ADIT Integrated Project (contract number LSHB-CT-2005511065)
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
LC-MS at core of university-industry link
No full textLC-MS at core of university-industry link Thermo Fisher Scientific (TFS) and the Department of Systems Biology at the Technical University of Denmark, (DTU),have formed a collaboration to pursue breakthroughs in the understanding of how cellular protein networks drive important diseases by exploiting liquid chromatography coupled to mass spectrometry (LC-MS). TFS will provide early access to new technology and designs, and DTU proteomics scientists will rovide feedback and collaborate on new applications. The centerpiece of this collaboration is a new proteomics laboratory in Lyngby, Denmark, equipped with the latest LC-MS technology, including the TFS Orbitrap Fusion Tribrid LC-MS system that offers unprecedented depth of analysis of biological samples.‘‘Studying the dynamic rewiring of cellular signaling networks requires state-ofthe-art mass spectrometry,’’ said DTU’s Professor Rune Linding (Fig. 8). ‘‘The Orbitrap Fusion system enables us to push the boundaries and to analyze completely new avenues of cellular decision processes, and to perform genome-scale studies of how the dynamics in these networks affect cell behavior.This is crucial, as it is now clear that the progression of complex diseases, such as cancer, is due to changes in these molecular networks. ‘‘We were extremely excited to see, only a few days after installation, the Orbitrap Fusion system generate the best MS/MS data we have ever seen for the characterization of phosphorylation sites on critical tumor samples.’’ ‘‘We are immensely pleased to be working with this talented and motivated team of scientists,’’ said Iain Mylchreest, vice president, research and development, life science mass spectrometry, TFS. ‘‘We share with them the objective of pushing the limits of science to make the world a better place, and the Orbitrap Fusion Tribrid system is designed for precisely this type of visionary research.’’ DTU is establishing the state-of-the-art laboratory to develop new experiments to dig deeper into the core machinery of the cell. The new laboratory will use four TFS QExactive LC-MS/MS systems, and nano-LC 1000 systems along with one of the first TFS Orbitrap Fusion Tribrid systems to leave the factory since its June 2013 debut
Decoding network dynamics in cancer
No full textBiological systems are composed of highly dynamic and interconnected molecular networks that drive biological decision processes. The goal of network biology is to describe, quantify and predict the information flow and functional behaviour of living systems in a formal language and with an accuracy that parallels our characterisation of other physical systems such as Jumbo-jets. Decades of targeted molecular and biological studies have led to numerous pathway models of developmental and disease related processes. However, so far no global models have been derived from pathways, capable of predicting cellular trajectories in time, space or disease. The development of high-throughput methodologies has further enhanced our ability to obtain quantitative genomic, proteomic and phenotypic readouts for many genes/proteins simultaneously. Here, I will discuss how it is now possible to derive network models through computational integration of systematic, large-scale, high-dimensional quantitative data sets. I will review our latest advances in methods for exploring phosphorylation networks. In particular I will discuss how the combination of quantitative mass-spectrometry, systems-genetics and computational algorithms (NetworKIN [Linding et al. Cell 2007] and NetPhorest [Miller et al. Science Signaling 2008]) made it possible for us to derive systems-level models of JNK and EphR signalling networks [Bakal et al. Science 2008, Jørgensen et al. Science 2009]. I shall discuss work we have done in comparative phospho-proteomics and network evolution [Tan et al. Science Signaling 2009, Tan et al. Science 2009, Tan et al. Science 2011]. Finally, I will discuss our most recent work in analyzing genomic sequencing data from NGS studies and how we have developed new powerful algorithms to predict the impact of disease mutations on cellular signaling networks [Creixell et al. Nature Biotechnology 2012, Erler & Linding Cell 2012, Horn et al. Nature Methods 2014]
Variations on the Author
Get PDF“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
Get PDFWe 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
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe 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
Shapes of cell signaling
Get PDFCell signaling is a complex process organized in time and space. Signal transduction is constantly modulated by cell-intrinsic and cell-extrinsic input cues and the resulting phenotypic responses such as morphological can feed back into the system. This provides cells with a responsive, accurate, and rugged system to deal with changes in the surroundings or the genome. Whilst signaling networks (dynamic transient protein–protein interactions modulated by post-translational modifications in response to input cues) have been researched for decades, further analysis of their spatial organization is critical for both basic and disease biology and will benefit from recent advances in computational modeling and image analysis using deep/machine learning and in microscopy and imaging. Furthermore, mathematical modeling with reaction-diffusion approaches on time-varying geometries complements the investigations, allowing to conceptualize the organizational principles of signaling and information transduction in the four dimensions of time and space.Peer Reviewe
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