1,720,986 research outputs found
MIRROR: a miRNA regulation-level network-based algorithm to study sexual dimorphism in cancer
Get PDFOne of the open challenges in precision medicine, whose importance is growing every day, is sex-specific medicine: the study of how sex-based biological differences influence people’s health. These differences can be measured in terms of disease incidence, prevalence, mortality, and survival. Understanding the leading causes of these disparities is therefore of the utmost importance. With recent advancements in high-throughput technologies, large-scale molecular data are being generated for individual cancer patients; however, extracting meaningful insights from these complex datasets and translating them into clinical applications remains a challenge. Moreover, the functional interdependencies between the molecular components in a human cell often reflect the perturbations of a complex intracellular and intercellular network. Network-based approaches, being inherently holistic, can lead to a better understanding of the molecular mechanisms underlying a disease. For these reasons, this project focuses on the development of a network-based method to investigate sexual dimorphism in cancer using transcriptomic data. Many have already investigated transcriptomic data in this context, with particular interest in the role of miRNAs, showing the involvement of these regulatory elements in differentiating patients by sex in different types of cancer. However, these studies focus only on evaluating changes in the expression level, without conducting a more comprehensive analysis of miRNA expression and without investigating miRNAs’ targets. The aim of this project is therefore to carry out a multi- layer study involving both miRNAs and their target genes’ expression data. In particular, it focuses on the development of a novel and generalizable algorithm (MIRROR), which can be used on cancer patients to help identify key regulatory mechanisms and molecules that act as differentiators between males and females. Here we implemented and tested MIRROR on three different cancers (colon adenocarcinoma, hepatocellular carcinoma, and low-grade gliomas) and assessed its performance by comparing it to other state-of-the-art approaches. By doing so we proved MIRROR’s efficacy in identifying sex-specific key genes, presenting it as a viable alternative to the state-of-the-art methods which failed to capture these differences. Moreover, we also showed how the genes identified by MIRROR can be integrated with clinical features
The Ball and Chain of Polyubiquitin Structures
Get PDFUbiquitylation is a post-translational modification implicated in several different cellular pathways. The possibility of forming chains through covalent crosslinking between any of the seven lysines, or the initial methionine, and the C terminus of another moiety provides ubiquitin (Ub) with special flexibility in its function in signalling. Here, we review the knowledge accumulated over the past several years about the functions and structural features of polyUb chains. This analysis reveals the need to understand further the functional role of some of the linkages and the structural code that determines recognition of polyUbs by protein partners. Ubiquitin (Ub), a small signalling protein, forms chains as a result of covalent linkage between any of the seven lysines or the N-terminal methionine of one subunit and the C terminus of another Ub.PolyUb chains both with the same or mixed linkages are involved in several cellular functions from proteasomal targeting to protein regulation and have thus acquired an enormous importance in cellular signalling.PolyUbs exhibit a unique repertoire of conformational states that is dependent on the specific linkages, which have different flexibilities.Further complexity is added by the interaction of polyUbs with cellular partners, which modulate their structure and functions.Understanding the structural and functional aspects of the polyUb code continues to offer an important challenge
The missing links to link ubiquitin: Methods for the enzymatic production of polyubiquitin chains
Get PDFAbstractAttachment of ubiquitin (Ub) as monoUb and polyUb chains of different lengths and linkages to proteins plays a dominant role in very different regulatory mechanisms. Therefore, the study of polyUb chains has assumed a central interest in biochemistry and structural biology. An essential step necessary to allow in vitro biochemical and structural studies of polyUbs is the production of their chains in high quantities and purity. This is not always an easy task and can be achieved both enzymatically and chemically. Previous reviews have covered chemical cross-linking exhaustively. In this review, we concentrate on the different approaches developed so far for the enzymatic production of different Ub chains. These strategies permit a certain flexibility in the production of chains with various linkages and lengths. We critically describe the available methods and comment on advantages and limitations. It is clear that the field is mature to study most of the possible links, but some more work needs to be done to complete the picture and to exploit the current methodologies for understanding in full the Ub code
Differential Co-expression Network Analysis to Investigate Sexual Dimorphism in Colon Cancer
No full textColorectal cancer is the third most diagnosed cancer in the world, but it has a higher mortality rate in men compared to women. However, we are not close to understanding how and why sex influences the outcome of the disease. This study focuses on mRNA expression profiles of colon cancer patients to look for molecular differences in the development of colon cancer between men and women. We used paired expression data (i.e., data collected in pairs of normal and cancer cells, by taking samples from the same individual), we identified differentially expressed genes (cancer vs normal) and computed co-expression and differential co-expression gene networks (men vs women). Doing so, we inferred the main changes and alterations happening in cancer tissues, and specifically how these changes were different among men and women. We found that the co-expression networks of women and men affected by colon cancer are quite different and we reported the genes that show the most differences in this comparison, checking if they could also be associated to sexual dimorphism or sexual hormones. Among these genes we found a interesting presence of genes associated to the Wnt signaling pathway which has been found to be regulated by estrogen and whose activation is strongly linked with colon cancer
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
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