1,721,026 research outputs found
Confounding Factor Correction For Accurate Expression Quantitative Trait Loci Discovery
Get PDFExpression quantitative trait loci (eQTL) have become an attractive research topic in the past decade assisted by the technical advances in next-generation sequencing (NGS) and high-throughput gene expression measurements. eQTL discoveries provided researchers with new insights into genetic regulatory mechanisms, and are crucial in establishing functional links in genome-wide association study (GWAS) results. A powerful aspect of these studies are that the simultaneous genome wide measurements of gene expression values and sequence variants make it possible to detect associations independent of prior knowledge. However, the high dimensionality of the data also creates multiple challenges in the analysis process. Population structure in genotype data can induce significant inflation in the results leading to false positive findings, and confounding factors in gene expression measurements, such as technical batch effects and environmental differences, can lower the detection power of small genetic effects. The focus of this thesis is on the challenges in analyzing high-dimensional gene expression data to increase the accuracy in eQTL discovery. A central problem in developing confounding factor correction methods for eQTL analysis is to account for non-genetic confounding factors, while preventing broad impact genetic effects of being modeled as non-genetic variation. To address this issue, we developed a novel method CONFETI: CONfounding Factor Estimation Through Independent component analysis. CONFETI is based on a linear mixed model framework and uses independent component analysis (ICA) to estimate statistically independent generative sources from the observed gene expression profiles. Candidate genetic effects are excluded from the correction to maximize the discovery of broad impact eQTL, using the estimated independent components. We evaluated our framework by comparing the performance to other published confounding factor correction methods using both simulated and real human data. In the analysis of simulated data, we show that CONFETI most accurately recovered simulated eQTL results in the presence of confounding factors by distinguishing genetic effects from non-genetic variance.We then analyzed matched twin pair datasets from the Multiple Tissue Human Expression Resource (MuTHER) consortium and datasets consisting of similar tissue pairs from the Genotype-Tissue Expression (GTEx) consortium. To assess the performance of each method in human data, we investigated the replication of cis and trans-eQTL identified in each dataset. We found that accounting for confounding factors greatly increased both the number of identified cis-eQTL in each dataset, and replicating cis-eQTL between twin pairs and similar tissue types. The number of identified trans-eQTL increased as well, however, most of the findings were specific to each dataset and the replication rate remained significantly lower compared to cis-eQTL. While the use of confounding factor correction methods increased the power of the analysis, we found little difference in identifying replicating cis and trans-eQTL in human data by removing candidate genetic effects prior to correction
A Novel Asymptotically Correct Statistic For Detecting Pairwise And Higher Order Concordant Epistasis Across Multiple Quantitative Traits
Get PDFDriven by the efficiency of DNA sequencing and related technologies, genome- and epigenome-wide association studies have already proven successful at producing specific results and general insights about the nature of genomic regulation. Discovery of expression Quantitative Trait Loci (eQTL), differentially methylated regions (DMRs), and other genomic and epigenetic features are proving integral to our understanding of how gene expression and DNA methylation (DNAm) are controlled throughout the human body and are changing how genomic and epigenetic data are analyzed in the study of cellular processes and complex diseases. Epistasis is the interaction among multiple genetic loci in their effect on gene expression. While epistasis is pervasive in biological systems and has the potential to account for heritability in traits that remain unexplained by the sum of main effects, the computational and statistical challenges of epistasis detection are daunting. We present the F-test of magnitude and concordance (Fomac) - a novel statistic that detects concordant epistasis across multiple datasets or co-expressed genes by constraining linear model parameters to be both significant and consistent. Simulations were carried out to compare the performance of Fomac to that of comparable methods for detecting single- and multi-trait epistasis, and they showed that Fomac is able to leverage concordant effects for improved statistical power. Fomac was also applied to gene expression from the Multiple Tissue Human Expression Resource (MuTHER) where a genome-wide analysis across 3 tissues identified 2754 examples of gene-wise Bonferroni-significant concordant epistasis. Epigenome-wide association studies (EWAS) are providing another angle from which to view genetic regulation. We performed an EWAS comparing the methylome of circulating monocytes in patients with and without Charcot foot (a devastating complication of diabetes.) Increased osteoclast activity has a role in the disease, and osteoclasts derived from monocytes are particularly well-suited for such a role. We observed that the methylome of these monocytes was significantly different in patients with and without Charcot foot, and identified specific genes with aberrant methylation. Together, the studies described in this dissertation serve the notion that by understanding relationships between and within omics data, we can both glean useful insights into specific regulatory mechanisms of the cell and apply patterns to accurately predict biological response
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
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
- …
