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Estimation of population allele frequencies from small samples containing multiple generations. Series on Advances in Bioinformatics and Computational Biology
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RNA sequencing for the study of splicing
Full text linkAmongst the many processes that shape the final set of RNA molecules present in eukaryote cells, splicing emerges as the most prominent mechanism for message diversification. In recent years, applications of high throughput sequencing to RNA, known as RNA sequencing, have opened new avenues for the study of transcriptome composition, and have enabled further characterisation of such mechanism. In this thesis, I focus on the application of this technology to the study of human transcript diversity and its potential impact on the protein repertoire.
In the first results chapter, I explore the extent of transcriptome diversity by asking whether there is a preference for the production of specific alternative transcripts within each given gene. I show that while many alternative transcripts can be detected, the expression of most protein coding genes tends to be dominated by one single transcript (major transcript). Such findings are validated in the second chapter, and are further used to explore changes in splicing patterns in a disease context. By analysing healthy and tumor samples from kidney cancer patients, I show that most of the detected splicing alterations do not lead to big changes in the relative abundance of major transcripts, at least in a recurrent manner. In addition, I introduce a framework to visualise the most extreme changes in splicing and to evaluate their potential functional impact. In the third chapter, I investigate the role of spliceosome assembly dynamics on the regulation of splice site choice. I show that depletion of PRPF8, a core spliceosomal component, leads to the preferential retention of a subset of introns with weaker splice sites, and also introduces alterations in the rate of co-transcriptional splicing. Finally, in the last chapter, I explore the validation of changes in alternative transcript abundance at the protein level, through the integration of results derived from RNA sequencing datasets with those obtained from proteomics experiments.
Altogether, the findings described in this thesis provide a global picture on the extent of alternative splicing in the diversification of the transcriptome, expand current knowledge on the splicing reaction, and open new possibilities for the integration of transcriptomics and proteomics data
Estimation of population allele frequencies from small samples containing multiple generations
No full textEstimations of population genetic parameters like allele frequencies, heterozygosities, inbreeding coefficients and genetic distances rely on the assumption that all sampled genotypes come from a randomly interbreeding population or sub-population. Here we show that small cross-generational samples may severely affect estimates of allele frequencies, when a small number of progenies dominate the next generation or the sample. A new estimator of allele frequencies is developed for such cases when the kin structure of the focal sample is unknown and has to be assessed simultaneously. Using Monte Carlo simulations it was demonstrated that the new estimator delivered significant improvement over the conventional allele counting estimator
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
Editorial:THE RICH DIVERSITY OF GENOMICS—A REPORT ON THE ‘COMPARATIVE AND FUNCTIONAL GENOMICS (BITS) WORKSHOP’, HINXTON, UK, 27–30 OCTOBER 2005
Full text linkVariations 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
Author Correction: High-coverage whole-genome analysis of 1220 cancers reveals hundreds of genes deregulated by rearrangement-mediated cis-regulatory alterations
No full textAppropriate 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
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