273 research outputs found

    Optimising probe library design for DNA resequencing

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    EThOS - Electronic Theses Online ServiceGBUnited Kingdo

    Thermal equivalence of DNA duplexes for probe design

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    We present the theory of thermal equivalence in the framework of the Peyrard–Bishop model and some of its anharmonic variants. The thermal equivalence gives rise to a melting index ? which maps closely the experimental DNA melting temperatures for short DNA sequences. We show that the efficient calculation of the melting index can be used to analyse the parameters of the Peyrard–Bishop model and propose an improved set of Morse potential parameters. With this new set we are able to calculate some of the experimental melting temperatures to ± 1.2 °C. We review some of the concepts of sequencing probe design and show how to use the melting index to explore the possibilities of gene coverage by tuning the model parameters

    Thermal equivalence of DNA duplexes without calculation of melting temperature

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    The common key to nearly all processes involving DNA is the hybridization and melting of the double helix: from transmission of genetic information and RNA transcription, to polymerase chain reaction and DNA microarray analysis, DNA mechanical nanodevices and DNA computing. Selecting DNA sequences with similar melting temperatures is essential for many applications in biotechnology. We show that instead of calculating these temperatures, a single parameter can be derived from a statistical-mechanics model that conveniently represents the thermodynamic equivalence of DNA sequences. This parameter is shown to order experimental melting temperatures correctly, is much more readily obtained than the melting temperature, and is easier to handle than the numerous parameters of empirical regression models

    SLiMFinder: a web server to find novel, significantly over-represented, short protein motifs

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    Short, linear motifs (SLiMs) play a critical role in many biological processes, particularly in protein–protein interactions. The SLiMFinder (Short, Linear Motif Finder) web server is a de novo motif discovery tool that identifies statistically over-represented motifs in a set of protein sequences, accounting for the evolutionary relationships between them. Motifs are returned with an intuitive p¬-value that greatly reduces the problem of False Positives and is accessible to biologists of all disciplines. Input can be uploaded by the user or extracted directly from UniProt. Numerous masking options give the user great control over the contextual information to be included in the analyses. The SLiMFinder server combines these with user-friendly output and visualisations of motif context to allow the user to quickly gain insight into the validity of a putatively functional motif. These visualisations include alignments of motif occurrences, alignments of motifs and their homologues and a visual schematic of the top-ranked motifs. Returned motifs can also be compared to known SLiMs from the literature using CompariMotif. All results are available for download. The SLiMFinder server is available at: http://bioware.ucd.ie/slimfinder.html

    SLiMSearch 2.0: biological context for short linear motifs in proteins

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    Short, linear motifs (SLiMs) play a critical role in many biological processes. The SLiMSearch 2.0 (Short, Linear Motif Search) web server allows researchers to identify occurrences of a user-defined SLiM in a proteome, using conservation and protein disorder context statistics to rank occurrences. User-friendly output and visualizations of motif context allow the user to quickly gain insight into the validity of a putatively functional motif occurrence. For each motif occurrence, overlapping UniProt features and annotated SLiMs are displayed. Visualization also includes annotated multiple sequence alignments surrounding each occurrence, showing conservation and protein disorder statistics in addition to known and predicted SLiMs, protein domains and known post-translational modifications. In addition, enrichment of Gene Ontology terms and protein interaction partners are provided as indicators of possible motif function. All web server results are available for download. Users can search motifs against the human proteome or a subset thereof defined by Uniprot accession numbers or GO term. The SLiMSearch server is available at: http://bioware.ucd.ie/slimsearch2.html

    SLiMSearch: a webserver for finding novel occurrences of short linear motifs in proteins, incorporating sequence context

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    Short, linear motifs (SLiMs) play a critical role in many biological processes. The SLiMSearch (Short, Linear Motif Search) webserver is a flexible tool that enables researchers to identify novel occurrences of predefined SLiMs in sets of proteins. Numerous masking options give the user great control over the contextual information to be included in the analyses, including evolutionary filtering and protein structural disorder. User-friendly output and visualizations of motif context allow the user to quickly gain insight into the validity of a putatively functional motif occurrence. Users can search motifs against the human proteome, or submit their own datasets of UniProt proteins, in which case motif support within the dataset is statistically assessed for over- and under-representation, accounting for evolutionary relationships between input proteins. SLiMSearch is freely available as open source Python modules and all webserver results are available for download. The SLiMSearch server is available at: http://bioware.ucd.ie/slimsearch.htm

    Ceum air Cheum: Cruinneachadh de dhàintean nas fhaide = Step by Step: A Book of Longer Poems

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    This is Christopher Whyte's sixth collection. Ceum air Cheum features 12 longer poems. Its European range, modernity of tone and challenging subject matter mark this book out as a major event in Gaelic poetry. Facing translations into English are by Niall O’Gallagher and the author

    Alexandria: A City and Myth

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    Synopsis Alexandria was one of the most important cities of the ancient world, with achievements in the arts, sciences and religion. For the first time the author seeks to understand the wider picture, the longer period of evolution as a city, as both an urban concept and a literary and historical ideal. He does this by bringing together the disciplines of archaeology (including his own recent fieldwork), anthropology, history, geography, oral history, art and literature. As a result Alexandria is seen as a unique example of African urbanism, an Egyptian city facing the wider Mediterranean world, which became an archetype for social, religious and cultural cosmopolitanism. A work for undergraduates and postgraduates in the disciplines of classical and Egyptian archaeology, historical geography, art history, oriental studies and general history

    Optimal probe length varies for targets with high sequence variation: implications for probe library design for resequencing highly variable genes

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    BackgroundSequencing by hybridisation is an effective method for obtaining large amounts of DNA sequence information at low cost. The efficiency of SBH depends on the design of the probe library to provide the maximum information for minimum cost. Long probes provide a higher probability of non-repeated sequences but lead to an increase in the number of probes required whereas short probes may not provide unique sequence information due to repeated sequences. We have investigated the effect of probe length, use of reference sequences, and thermal filtering on the design of probe libraries for several highly variable target DNA sequences.ResultsWe designed overlapping probe libraries for a range of highly variable drug target genes based on known sequence information and develop a formal terminology to describe probe library design. We find that for some targets these libraries can provide good coverage of a previously unseen target whereas for others the coverage is less than 30%. The optimal probe length varies from as short at 12 nt to as large as 19 nt and depends on the sequence, its variability, and the stringency of thermal filtering. It cannot be determined from inspection of an example gene sequence.ConclusionsOptimal probe length and the optimal number of reference sequences used to design a probe library are highly target specific for highly variable sequencing targets. The optimum design cannot be determined simply by inspection of input sequences or of alignments but only by detailed analysis of the each specific target. For highly variable sequences, shorter probes can in some cases provide better information than longer probes. Probe library design would benefit from a general purpose tool for analysing these issues. The formal terminology developed here and the analysis approaches it is used to describe will contribute to the development of such tools

    Deleuze and the author

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    This thesis argues that Gilles Deleuze, as philosopher, reader, and critic, recognised the central importance of a defined authorial subjectivity, closely associated with a philosophical or intellectual project, and that his analyses of philosophy, literature, visual art and cinema were shaped and determined by his recognition of that authority. In this respect, my reading challenges those critics who find in the work of Deleuze an assault on ‘author-centric’ interpretations of texts, and more generally on the concept of a unified self, and which uphold experimentation on the part of the reader or critic rather than interpretation. I argue that Deleuze has a coherent and meaningful conception of an author as a consciousness which persists through time, learns, plans and makes projects, differentiates itself from the work of other authors, is inspired and creative, takes positions in relation to the inheritance of artistic and philosophical traditions, and which is capable of entering into collaboration with others. Through close reading of Deleuze’s texts, I demonstrate that he consistently relies on the authorial function to impose unity and coherence on the distinctive - and often remarkable - body of work of an individual theorist or practitioner. I argue that the historical, political and social situation of an author is of great importance to the analysis of a text. Finally, unlike Roland Barthes or other critics invested in the ‘death’ or displacement of the author, I argue that Deleuze considers the competing interpretations of a text advanced by the reader or spectator to be of little or no importance
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