1,720,959 research outputs found
The Proteomics Identifications database: 2010 update
Get PDFThe Proteomics Identifications database (PRIDE, http://www.ebi.ac.uk/pride) at the European Bioinformatics Institute has become one of the main repositories of mass spectrometry-derived proteomics data. For the last 2 years, PRIDE data holdings have grown substantially, comprising 60 different species, more than 2.5 million protein identifications, 11.5 million peptides and over 50 million spectra by September 2009. We here describe several new and improved features in PRIDE, including the revised submission process, which now includes direct submission of fragment ion annotations. Correspondingly, it is now possible to visualize spectrum fragmentation annotations on tandem mass spectra, a key feature for compliance with journal data submission requirements. We also describe recent developments in the PRIDE BioMart interface, which now allows integrative queries that can join PRIDE data to a growing number of biological resources such as Reactome, Ensembl, InterPro and UniProt. This ability to perform extremely powerful across-domain queries will certainly be a cornerstone of future bioinformatics analyses. Finally, we highlight the importance of data sharing in the proteomics field, and the corresponding integration of PRIDE with other databases in the ProteomExchange consortium.European Union (ProDaC grant LSHG-CT-2006-036814)Burroughs Wellcome Fund (Grant WT085949MA
Multivariate methods for the statistical analysis of hyperdimensional high-content screening data
No full textThesis: Ph. D., Massachusetts Institute of Technology, Computational and Systems Biology Program, 2014.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references.In the post-genomic era, greater emphasis has been placed on understanding the function of genes at the systems level. To meet these needs, biologists are creating larger, and increasingly complex datasets. In recent years, high-content screening (HCS) using RNA interference (RNAi) or other perturbation techniques in combination with automated microscopy has emerged as a promising investigative tool to explore intricate biological processes. Image-based HC screens produce massive hyperdimensional data sets. To identify novel components of the DNA damage response (DDR) after ionizing radiation, we recently performed an image-based HC RNAi screen in an osteosarcoma cell line. Robust univariate hit identication methods and manual network analysis identied an isoform of BRD4, a bromodomain and extra-terminal domain family member, as an endogenous inhibitor of DDR signaling. However, despite the plethora of data generated from our and other HC screens, little progress has been made in analyzing HC data using multivariate computational methods that exploit the full richness of hyperdimensional data and identify more than just the most salient knockdown phenotypes to gain a detailed understanding of how gene products cooperate to regulate complex cellular processes. We developed a novel multivariate method using logistic regression models and least absolute shrinkage and selection operator regularization for analyzing hyperdimensional HC data. We applied this method to our HC screen to identify genes that exhibit subtle but consistent phenotypic changes upon knockdown that would have been missed by conventional univariate hit identication approaches. Our method automatically selects the most predictive features at the most predictive time points to facilitate the more ecient design of follow-up experiments and puts the identied hits in a network context using the Prize-Collecting Steiner Tree algorithm. This method offers superior performance over the current gold standard for the analysis of HC RNAi screens. A surprising finding from our analysis is that training sets of genes involved in complex biological phenomena used to train predictive models must be broken down into functionally coherent subsets in order to enhance new gene discovery. Additionally, we found that in the case of RNAi screening, statistical cell-to-cell variation in phenotypic responses in a well of cells targeted by a single shRNA is an important predictor of gene dependent events.by Jonathan Rameseder.Ph. D
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
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
Proteasome Inhibitors Block DNA Repair and Radiosensitize Non-Small Cell Lung Cancer
No full textDespite optimal radiation therapy (RT), chemotherapy and/or surgery, a majority of patients with locally advanced non-small cell lung cancer (NSCLC) fail treatment. To identify novel gene targets for improved tumor control, we performed whole genome RNAi screens to identify knockdowns that most reproducibly increase NSCLC cytotoxicity. These screens identified several proteasome subunits among top hits, including the topmost hit PSMA1, a component of the core 20 S proteasome. Radiation and proteasome inhibition showed synergistic effects. Proteasome inhibition resulted in an 80–90% decrease in homologous recombination (HR), a 50% decrease in expression of NF-κB-inducible HR genes BRCA1 and FANCD2, and a reduction of BRCA1, FANCD2 and RAD51 ionizing radiation-induced foci. IκBα RNAi knockdown rescued NSCLC radioresistance. Irradiation of mice with NCI-H460 xenografts after inducible PSMA1 shRNA knockdown markedly increased murine survival compared to either treatment alone. Proteasome inhibition is a promising strategy for NSCLC radiosensitization via inhibition of NF-κB-mediated expression of Fanconi Anemia/HR DNA repair genes.American Society for Radiation Oncology (Junior Faculty Career Research Training Award)Harvard University. Joint Center for Radiation Therapy (Foundation Grant)Dana-Farber/Harvard Cancer Center (SPORE Developmental Research Project Award in Lung Cancer Research)National Cancer Institute (U.S.) (Award K08CA172354
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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