1,720,959 research outputs found

    On the unranked topology of maximally probable ranked gene tree topologies

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    A ranked tree topology is a tree topology with a temporal ordering of its coalescence events. Under the multispecies coalescent model, we consider ranked gene tree topologies realized along the branches of ranked species trees, where one gene copy is sampled for each species. Previous results have demonstrated that for almost all ranked species tree topologies with at least five species, there exists a set of branch lengths such that the maximally probable ranked gene tree topologies-those generated with the highest probability under the model-do not match the species tree ranked topology. Here, we focus on the agreement of a ranked species tree with its maximally probable ranked gene tree topologies in terms of their unranked topology, that is, disregarding the ordering of the coalescence events. We show that although the set of maximally probable ranked gene tree topologies for a ranked species tree can contain ranked trees with different unranked topologies, at least one of these maximal ranked gene tree topologies must have the same unranked topology as the species tree. Our results contribute to the study of the relationships between gene trees and species trees

    GPCRome-wide analysis of G-protein-coupling diversity using a computational biology approach

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    Abstract GPCRs are master regulators of cell signaling by transducing extracellular stimuli into the cell via selective coupling to intracellular G-proteins. Here we present a computational analysis of the structural determinants of G-protein-coupling repertoire of experimental and predicted 3D GPCR-G-protein complexes. Interface contact analysis recapitulates structural hallmarks associated with G-protein-coupling specificity, including TM5, TM6 and ICLs. We employ interface contacts as fingerprints to cluster Gs vs Gi complexes in an unsupervised fashion, suggesting that interface residues contribute to selective coupling. We experimentally confirm on a promiscuous receptor (CCKAR) that mutations of some of these specificity-determining positions bias the coupling selectivity. Interestingly, Gs-GPCR complexes have more conserved interfaces, while Gi/o proteins adopt a wider number of alternative docking poses, as assessed via structural alignments of representative 3D complexes. Binding energy calculations demonstrate that distinct structural properties of the complexes are associated to higher stability of Gs than Gi/o complexes. AlphaFold2 predictions of experimental binary complexes confirm several of these structural features and allow us to augment the structural coverage of poorly characterized complexes such as G12/13

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

    EXPANSION: a webserver to explore the functional consequences of protein-coding alternative splice variants in cancer genomics

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    EXPANSION (https://expansion.bioinfolab.sns.it/) is an integrated web-server to explore the functional consequences of protein-coding alternative splice (AS) variants. We combined information from Differentially Expressed (DE) protein-coding transcripts from cancer genomics, together with domain architecture, protein interaction network, and gene enrichment analysis to provide an easy-to-interpret view of the effects of protein-coding splice variants. We retrieved all the protein-coding Ensembl transcripts and mapped Interpro domains and Post-translational modifications (PTMs) on canonical sequences to identify functionally relevant splicing events. We also retrieved isoform-specific protein-protein interactions (PPIs) and binding regions from IntAct to uncover isoform-specific functions via gene-sets over-representation analysis. Through EXPANSION, users can analyse pre-calculated or user-inputted DE transcript datasets, to easily gain functional insights on any protein spliceform of interest

    Variations on the Author

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    “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

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    We 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

    Interaction prediction at the domain level and its application to the analysis of LRRK2 interactome

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    Protein-protein interactions are often mediated by protein domains. Experimentally determining domain-domain interactions (DDIs) is expensive and time-consuming, so developing bioinformatic tools to predict DDIs would be crucial to break down the interaction network to the domain level resolution. In this work, we present a new DDI prediction model which combines various features, including coevolution, mutual information and common GO terms, in a machine learning framework. Predictions were further improved using the information of available 3D templates of the domain pair in publicly available structures. In order to add this feature to the model, we generated a 3D interacting domains catalog based on the InterPro domain definition. Our catalog extends the information provided by public resources such as 3did and could be readily used for structural annotation of interactomic studies. We then show the application of our DDI predictor to the analysis of an experimentally determined proximity interactome dataset of Parkinson’s disease-related protein LRRK2. The interaction probabilities provided by our model were used to distinguish between interactions associated with LRRK2 enzymatic activity (involving the catalytic core) and interactions involving more evolutionarily recent domains (ARM, ANK and WD40), which are likely involved in the functional specialization of LRRK2

    Dispelling the Myths Behind First-author Citation Counts

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    We 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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