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Statistical methods for transcription factor footprinting in 3D genome assays
No full textChromatin loops are drivers of gene regulation, bringing distal enhancers into close proximity with their target genes. While a subset of these long-range contacts are mediated by the architectural factors CTCF and cohesin, the mechanisms underlying the majority of these regulatory contacts remains unclear. While transcription factors and other proteins are known to be contributors to DNA looping, no methods currently exist for simultaneously profiling 3D genome structure and the DNA-binding proteins involved. This presents a significant limitation for evaluating transcription factor impact on 3D contacts and constructing high-resolution protein occupancy maps of regulatory regions. This dissertation seeks to bridge this gap by (1) developing statistical methods that quantitatively assess DNA-binding protein occupancy in 3D genome assays and (2) leveraging these new methods to (i) investigate the relationship between protein-binding and genome architecture and (ii) provide high-resolution maps of DNA-binding proteins at enhancers and promoters.
Chapter 1 proposes a statistical method that determines CTCF binding in CTCF MNase HiChIP assays. MNase, beyond its use in profiling genome structure, has also been used to determine transcription factor and nucleosome occupancy at high-resolution in assays like CUT&RUN and MNase-seq due to its endo-exonuclease activity, where it cuts regions unprotected by proteins and chews back the fragments until it reaches protein-protected DNA. This enables inference of both protein size and location, since nucleosomes protect more than twice the DNA of a transcription factor, thus yielding DNA fragments of significantly longer length. We leverage short, transcription factor (TF) protected fragments to pinpoint locations of CTCF binding at base-pair resolution. We then use TF-protected fragments at CTCF binding sites to implement a novel fragment-level view of CTCF-mediated chromatin looping dynamics. With this approach, we determine that fully extruded chromatin loops between convergent CTCF-bound sites are rare genome-wide and that, in addition to CTCF, active regulatory elements hinder cohesin-mediated loop extrusion. This supports a model by which the partially extruded chromatin loop can enable distal enhancer-promoter contacts.
Chapter 2 expands upon the method developed in Chapter 1 by broadly mapping locations of DNA-binding transcription factors in Micro-C. Unlike Chapter 1, Chapter 2 does not rely on a ChIP step to profile one protein’s occupancy. Not being limited to just investigating one protein, CTCF, facilitates additional novel insights into protein occupancy and their relation to 3D contacts and transcription. We find that expression level is tightly linked with the size of the nucleosome depleted region at the TSS and the presence of a large TF complex at the promoter, immediately upstream of the TSS, with unexpressed genes exhibiting a TSS obstructed by a nucleosome and a lack of TF binding. Furthermore, the TF-sized proteins upstream of the TSS at expressed genes appear to facilitate long-range, cohesin-independent looping contacts, which may partially explain why gene expression is largely maintained when cohesin is degraded. Further investigation into whether specific TFs may enable these long-range cohesin-independent contacts identified transcription factor motif families such as the KLF/SP and NF-Y motif families as likely candidates for cohesin-independent looping factors.
Chapter 3 applies the approach developed in Chapter 2 to gain a high-resolution view of the MYC oncogene and its distal cell-type specific enhancers. This analysis identifies MYC distal enhancers as regions highly occupied by TF-enhancer assemblies, which depend on RNA for their coalescence. This chapter reveals the cooperation between TF binding and RNA required for gene regulation and genome structure, and presents a framework for developing high-resolution maps of regulatory architecture.Biostatistic
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
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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