1,721,146 research outputs found
The estimation of relative site variability among aligned homologous protein sequences
No full textMotivation: Maximum likelihood-based methods to estimate site by site substitution rate variability in aligned homologous protein sequences rely on the formulation of a phylogenetic tree and generally assume that the patterns of relative variability follow a pre-determined distribution. We present a phylogenetic tree-independent method to estimate the relative variability of individual sites within large datasets of homologous protein sequences. It is based upon two simple assumptions. Firstly that substitutions observed between two closely related sequences are likely, in general, to occur at the most variable sites. Secondly that non-conservative amino acid substitutions tend to occur at more variable sites. Our methodology makes no assumptions regarding the underlying pattern of relative variability between sites.
Results: We have compared, using data simulated under a non-gamma distributed model, the performance of this approach to that of a maximum likelihood method that assumes gamma distributed rates. At low mean rates of evolution our method inferred site by site relative substitution rates more accurately than the maximum likelihood approach in the absence of prior assumptions about the relationships between sequences. Our method does not directly account for the effects of mutational saturation, However, we have incorporated an 'ad-hoc' modification that allows the accurate estimation of relative site variability in fast evolving and saturated datasets
A Support Vector Machine for the Discrimination of MicroRNA Precursors from Other Genomic Hairpin Structures
Full text linkMotivation: MicroRNAs (miRNAs) are endogenous, small (~ 20 nt), single-stranded, non-coding RNAs (ncRNAs) that result from the nuclear and cytoplasmic processing of transcribed precursor hairpin structures. They are increasingly recognized as playing crucial roles as post-transcriptional antisense regulators of gene expression through regulation of mRNA stability or translational efficiency. miRNAs, first reported in Caenorhabditis elegans, have been identified in the genomes of most higher organisms, including worms, flies, plants, mammals and recently in viruses.
Functional studies have shown that miRNAs play important roles in processes such as, cell proliferation, fat metabolism, apoptosis, neuronal cell fate, insulin secretion, haematopoietic differentiation and developmental regulation.
The detection of homologs of known miRNAs through comparative genomic approaches has proved relatively tractable. However, the ab-initio prediction of miRNA precursors through computational methods poses several additional difficulties, not least the fact that not all thermodynamically plausible transcribed hairpins are processed to yield mature miRNAs. It has not until now been possible to identify conserved sequence or structural elements that define consensus recognition elements for the enzymes that process miRNA precursors.
In the light of these observations we wished to develop and improve methods for the discrimination of true miRNA precursor hairpins from spurious hairpins
Methods: We have developed a SVM (Support Vector Machine) that considers up to 74 features associated with the primary and secondary structures and thermodynamic characteristics of candidate hairpin structures. We use a standard heuristic approach to optimize combinations of features used and train the SVM with sets of characterized hairpin miRNA precursors and known non-miRNA hairpins.
Results: Our SVM shows highly promising results in the discrimination of true miRNA precursors from “spurious” hairpins (typically around 95% sensitivity) in various species. In particular, our levels of false positive predictions appear to be low relative to comparable methods
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
Detection of alternative splicing in Vitis vinifera and validation by short sequencing reads
No full textVariations 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
Towards an integrated pipeline for the in-silico prediction of plant microRNAs and their precursors
Full text linkMicroRNAs (miRNAs) are endogenous, small (~ 20 nt), single-stranded, non-coding RNAs that result from the processing of transcribed precursor hairpin structures. They are increasingly recognized as playing crucial roles as post-transcriptional antisense regulators of gene expression through regulation of mRNA stability or translational efficiency.
The detection of homologs of known miRNAs through comparative genomic approaches has proved relatively tractable. However, the ab-initio prediction of potentially lineage-specific miRNA precursors through computational methods poses several additional difficulties, not least the fact that not all thermodynamically plausible transcribed hairpins are processed to yield mature miRNAs.
We have developed a Support Vector Machine that considers up to 78 features associated with the primary and secondary structures and thermodynamic characteristics of candidate hairpin structures. Our SVM is highly specific in the discrimination of true miRNA precursors from “spurious” hairpins with levels of false positive predictions that are low relative to comparable methods. We also show how our SVM functions as part of an in-silico pipeline for the prediction of novel miRNA precursors in plant genomes
Comparative and phylogenetic analysis of alpha-L-fucosidase genes
No full textFucosylated glycoconjugates play a role in a wide variety of biological processes, including immune responses, signal transduction, ontogenic events and pathogenesis of several human diseases. Alpha-L-fucosidases, which are responsible for their processing, have been demonstrated to be involved in lysosomal storage disease, inflammation, cystic fibrosis, cancer development and in the interactions between gametes in vertebrates as well as invertebrates. The sequence and comparative genomic analysis of these glycosyl hydrolases and the study of their evolutionary relationships appear therefore to be of considerable interest. In this work we carried out extensive similarity searches and comparative analyses to identify sequences encoding alpha-L-fucosidases. We have identified novel alpha-L-fucosidase coding sequences in worms, insects, sea urchin, ascidians, fish, chicken, amphibians, mammals and various bacteria resulting in a total of 39 alpha-L-fucosidase sequences. Two alpha-L-fucosidases that are present in all vertebrates likely reflect a distinct biological role for paralogous genes. Comparative sequence analysis of all metazoan alpha-L-fucosidases reveals a broad conservation of features, including the aspartate residue that constitutes the catalytic nucleophile. However, a cysteine which is thought to be part of the active site is also conserved in metazoa but not in arthropods, where it is replaced by an alanine. Phylogenetic analysis suggests a gene duplication event very early in metazoan evolution with the subsequent differential loss of isoforms in various metazoan lineages
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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