1,720,973 research outputs found
A holistic understanding of cancer genomics to inform treatment and research
No full textBackground:
The increase in volume of cancer genomic data has improved our understanding of cancer biology as well as laying the foundation for clinical precision oncology. The main limitation in this field now sits within the analytical methods, rather than data generation. Currently, there is no gold standard for analysing cancer next generation sequencing data. Therefore, we need to better understand the limitations of the available sequencing and bioinformatic analysis methods, in order to improve the use of DNA and RNA sequence data for cancer research and patient care.
Objectives:
To understand the validity and limitations of available bioinformatics methods then apply this knowledge to advance our understanding of (i) the genomic landscape of pancreatic neuroendocrine tumours and (ii) the expression patterns and biological impact of alternative RNA splice variants of TP53.
Methods:
To understand the validity of bioinformatic methods for studying tumours with few mutations and with substantial aneuploidy, I used simulated data containing known DNA sequence variants to evaluate different somatic single nucleotide variant calling methods and structural variant calling methods. Then, to assess whether TP53 splice variants can be quantitated accurately by current genomic and bioinformatic methods, simulated RNA sequencing data with known TP53 splice variant abundance was used, and the results compared with gold standard long digital PCR analysis.
Results:
I identified a list of clinically important single nucleotide variants likely to be missed by commonly used somatic DNA variant calling methods, and also determined the effectiveness and limitations of a range of methods for calling DNA structural variants. Analysis of combined clinicopathological and multi-omic data showed that pancreatic neuroendocrine tumours have a low number of somatic variants, and instead are characterised by extensive
aneuploidy, with the pattern of aneuploidy linked with patient outcome. I then showed that RNA sequencing has difficulty quantitating low abundance TP53 transcripts, especially transcripts expressed <1,000 copies/ug of RNA.
Conclusion:
The distinct patterns of aneuploidy in pancreatic neuroendocrine tumours are strongly associated with patient outcome in two thirds of patients in our study. These patterns are potentially valuable for clinical decision making. My identification of ‘false negative’ errors in SNV calling suggests that the use of variant calling software ‘out of the box’ may be missing clinically important variants. Based on a detailed investigation of the accuracy of RNA-seq analysis for TP53 RNA splicing variants, I propose caution when interpreting sequencing analysis of TP53 RNA splicing, and suggest this finding may be generalised to other genes. The results from my thesis suggest that as more bioinformatic methods are developed, there is a continuous need to evaluate them, understand their limitations and ensure their suitability to address specific research questions
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
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
TP53 gene mutation status and alternative transcript abundance in breast cancer of young women
No full textBreast cancer is the most commonly diagnosed malignancy in women worldwide, with approximately 13% being pre-menopausal or under 45 years old. Recent studies have shown that a higher percentage of these young women present with aggressive breast cancer subtypes, such as TNBC and HER2+, resulting in poorer prognosis and mortality.
These aggressive subtypes of breast cancer have been found to have more somatic mutations, such as mutations in the TP53 gene. TP53 is a tumour suppressor gene that modulates the cell cycle and prevents the replication of cells with damaged DNA. The TP53 gene expresses multiple RNA transcripts encoding different p53 protein isoforms via various mechanisms. Quantitation of these transcripts has proved challenging as all the transcripts share the common central 5 exons. Nevertheless, quantitation of the various 5’ and 3’ ends of the TP53 transcripts has suggested an association with specific biological responses. Researchers have studied the role of the TP53 gene and its isoforms in breast cancer; however, a lot is still unknown about TP53 in the context of breast cancer.
Due to technological limitations, detection, and quantitation of specific TP53 alternative transcripts expressed in tumours have been limited to amplifying and mapping short sequencing reads and then inferring the abundance of individual transcripts. To understand the role of TP53 in breast cancer, especially in tumourigenesis, a more comprehensive approach is required, including using novel approaches to detect and sequence the full-lengths of specific TP53 transcripts, such that this information can be integrated with mutation status and clinicopathological characteristics of the cancer to develop better prognostic tests.
This study was done in two parts; firstly, a bioinformatic component that used publicly available genomic data to investigate the TP53 mutational status and the predicted TP53 transcript expression levels in young and older women. Secondly, a laboratory component that analysed breast tumours from New Zealand (NZ) women. This utilised and subsequently developed new techniques to accurately detect and quantitate both TP53 transcripts and provided a greater knowledge of the repertoire of TP53 transcripts expressed in these tumour samples. The success of this study has the potential to transform TP53 research, by enabling an understanding of how various TP53 gene mutations might manifest themselves by providing the entire repertoire of transcripts that are expressed from the TP53 gene locus
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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