67 research outputs found
GeneSigDB: a manually curated database and resource for analysis of gene expression signatures
GeneSigDB (http://www.genesigdb.org or http://compbio.dfci.harvard.edu/genesigdb/) is a database of gene signatures that have been extracted and manually curated from the published literature. It provides a standardized resource of published prognostic, diagnostic and other gene signatures of cancer and related disease to the community so they can compare the predictive power of gene signatures or use these in gene set enrichment analysis. Since GeneSigDB release 1.0, we have expanded from 575 to 3515 gene signatures, which were collected and transcribed from 1604 published articles largely focused on gene expression in cancer, stem cells, immune cells, development and lung disease. We have made substantial upgrades to the GeneSigDB website to improve accessibility and usability, including adding a tag cloud browse function, facetted navigation and a âbasketâ feature to store genes or gene signatures of interest. Users can analyze GeneSigDB gene signatures, or upload their own gene list, to identify gene signatures with significant gene overlap and results can be viewed on a dynamic editable heatmap that can be downloaded as a publication quality image. All data in GeneSigDB can be downloaded in numerous formats including .gmt file format for gene set enrichment analysis or as a R/Bioconductor data file. GeneSigDB is available from http://www.genesigdb.org
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Discovering Causal Signaling Pathways Through Gene-Expression Patterns
High-throughput gene-expression studies result in lists of differentially expressed genes. Most current meta-analyses of these gene lists include searching for significant membership of the translated proteins in various signaling pathways. However, such membership enrichment algorithms do not provide insight into which pathways caused the genes to be differentially expressed in the first place. Here, we present an intuitive approach for discovering upstream signaling pathways responsible for regulating these differentially expressed genes. We identify consistently regulated signature genes specific for signal transduction pathways from a panel of single-pathway perturbation experiments. An algorithm that detects overrepresentation of these signature genes in a gene group of interest is used to infer the signaling pathway responsible for regulation. We expose our novel resource and algorithm through a web server called SPEED: Signaling Pathway Enrichment using Experimental Data sets. SPEED can be freely accessed at http://speed.sys-bio.net/
Meta-analysis of muscle transcriptome data using the MADMuscle database reveals biologically relevant gene patterns
<p>Abstract</p> <p>Background</p> <p>DNA microarray technology has had a great impact on muscle research and microarray gene expression data has been widely used to identify gene signatures characteristic of the studied conditions. With the rapid accumulation of muscle microarray data, it is of great interest to understand how to compare and combine data across multiple studies. Meta-analysis of transcriptome data is a valuable method to achieve it. It enables to highlight conserved gene signatures between multiple independent studies. However, using it is made difficult by the diversity of the available data: different microarray platforms, different gene nomenclature, different species studied, etc.</p> <p>Description</p> <p>We have developed a system tool dedicated to muscle transcriptome data. This system comprises a collection of microarray data as well as a query tool. This latter allows the user to extract similar clusters of co-expressed genes from the database, using an input gene list. Common and relevant gene signatures can thus be searched more easily. The dedicated database consists in a large compendium of public data (more than 500 data sets) related to muscle (skeletal and heart). These studies included seven different animal species from invertebrates (<it>Drosophila melanogaster, Caenorhabditis elegans</it>) and vertebrates (<it>Homo sapiens, Mus musculus, Rattus norvegicus, Canis familiaris, Gallus gallus</it>). After a renormalization step, clusters of co-expressed genes were identified in each dataset. The lists of co-expressed genes were annotated using a unified re-annotation procedure. These gene lists were compared to find significant overlaps between studies.</p> <p>Conclusions</p> <p>Applied to this large compendium of data sets, meta-analyses demonstrated that conserved patterns between species could be identified. Focusing on a specific pathology (Duchenne Muscular Dystrophy) we validated results across independent studies and revealed robust biomarkers and new pathways of interest. The meta-analyses performed with MADMuscle show the usefulness of this approach. Our method can be applied to all public transcriptome data.</p
TGF-ÎČ, WNT, AND FGF SIGNALING PATHWAYS DURING AXOLOTL TAIL REGENERATION AND FORELIMB BUD DEVELOPMENT
Tgf-ÎČ, Wnt, and Fgf signaling pathways are required for many developmental processes. Here, I investigated the requirement of these signaling pathways during tail regeneration and limb development in the Mexican axolotl (Ambystoma mexicanum).
Using small chemical inhibitors during tail regeneration, I found that the Tgf-ÎČ signaling pathway was required from 0-24 and 48-72 hours post tail amputation (hpa), the Wnt signaling pathway was required from 0-120 hpa, and the Fgf signaling pathway was required from 0-12hpa. Tgf-ÎČ1 was upregulated after amputation and thus may mediate Tgf-ÎČ signaling pathway during tail regeneration. Both Smad-mediated and non-Smad mediated Tgf-ÎČ signaling were activated as early as 1hpa. Smad-mediated Tgf-ÎČ signaling via activated pSmad2 and pSmad3, and via phosphorylated Erk and Akt. Two different Tgf-ÎČ signaling pathway inhibitors, SB505124 and Naringenin, differentially regulated pSmad2, pSmad3, p-Erk, and p-Akt, while SB505124 and Naringenin both inhibited tail regeneration; only SB505124 reduced cell proliferation. Wnt/ÎČ-Catenin signaling was increased and was enhanced by Wnt-C59. Disruption of the Wnt signaling pathway directly or indirectly activated Erk and Akt signaling. Disruption of the Fgf signaling pathway decreased p-Erk and increased p-Akt. All three signaling pathways affected cell proliferation and mitosis during tail regeneration.
The Wnt pathway inhibitor Wnt-C59 prevented forelimb bud outgrowth. The critical window for Wnt signaling regulating forelimb bud outgrowth was approximately developmental stage 40-42. Wnt signaling ligand Wnt3a and tight junction protein Zo-1 were expressed in the epidermis of the forelimb bud and both were down-regulated by Wnt-C59. Moreover, both Wnt and Fgf signaling pathways affected cell proliferation and mitosis of mesodermal cells during forelimb bud outgrowth.
Overall, my results show that Tgf-ÎČ, Wnt, and Fgf signaling pathways are required for axolotl tail regeneration. All three pathways affect Erk and Akt signaling and guide cell proliferation and mitosis. The Wnt signaling pathway is required for forelimb bud outgrowth, and it appears to regulate expression of Wnt3a and Zo1, and control cell proliferation and mitosis of mesodermal cells underlying the forelimb epidermis. These data enrich understanding of signaling network dynamics that underlie tissue regeneration and vertebrate limb development
Blanket stories and blurring binaries: contemporary Native American art and the discourse of authorship
M.A. in Art History--University of Oklahoma, 2015Includes bibliographical references.This thesis explores the relationship between Native American art and the recent rise in
participatory art. In this thesis I question the precedents for the subversion of single
authorship and collective creation, how Native American artists assert and articulate
indigenous epistemologies through contemporary practices, and what form it takes
when Native artists internalize Euro-American artistic practices and blur the influences
between indigenous and Western backgrounds. The current discourse on participatory art and social engagement construes it as an unprecedented phenomenon, which fails to take into account intercultural exchange between Western art and art from other cultural traditions. I argue that contemporary participatory art and traditional Native American art share a subversion of the solo artist and invoke contemporary Native participatory artists to demonstrate how the lack of a Great Artist tradition allows for more fluid--authorship in order to destabilize the binary opposition between collective and individual artistic production. This fluid authorship also articulates visual sovereignty for contemporary Native artists who are free to explore more traditional artistic practices. This thesis seeks to locate contemporary Native American art within a broader global contemporary context by investigating how cross-cultural exchange
shapes contemporary art
Play Among Books
How does coding change the way we think about architecture? Miro Roman and his AI Alice_ch3n81 develop a playful scenario in which they propose coding as the new literacy of information. They convey knowledge in the form of a project model that links the fields of architecture and information through two interwoven narrative strands in an âinfinite flowâ of real books
The Dangerous/Endangered Modern Woman in Four Interwar Spanish Novels (1917-1936)
The Modern Woman was a figure perpetually discussed in the early twentieth century, as she embodied the increasingly public role and greater mobility of women in industrialized cities. A century later, historians and literary critics still explore the significance of this female archetype, who was at the center of debates regarding feminism and changing gender dynamics, because the Modern Womanâs defiance of social conventions opened the way for the independent lifestyle and freedoms of women today. Yet, still left unexplored is the image of the Modern Woman as both dangerous and in danger and what this contradictory depiction reveals about beliefs regarding the right of women to access spaces and employment traditionally reserved for men, which continue to manifest in prohibitive practices like sexual discrimination and harassment. Through the analysis of four novelsâLa rampa by Carmen de Burgos, La Venus mecaÌnica by JoseÌ DiÌaz FernaÌndez, Eva Libertaria by Rafael LoÌpez de Haro, and Cristina GuzmaÌn, profesora de idiomas by Carmen de Icazaâthis study elucidates the dichotomy of the dangerous/endangered Modern Woman in literature of Interwar-era Spain, between the end of World War I and the start of the Spanish Civil War.
Representations of the Modern Woman exposed to danger often served as literary proof of her unsuitability for employment and the need for male protection to usher her back into the domestic realm. Less commonly, these depictions served to raise awareness of the exploitation, unfit work conditions, and insufficient wages that women experienced in the city, in works like La rampa and La Venus mecaÌnica, which call for social and economic reforms, or revolution, to oppose patriarchal, capitalist institutions. In contrast, the frivolous Modern Woman is an agent of disorder who threatens to dismantle the traditional family structure in Eva Libertaria and Cristina GuzmaÌn, profesora de idiomas. Furthermore, male anxieties about androgyny, unrestrained female sexuality, and the womenâs emancipation movement are evident in La Venus mecaÌnica and Eva Libertaria, in which female characters manipulate or emasculate men. These conflicting images reflect fears of rapidly changing gender roles and illustrate the difficulties that women faced in Spanish urban centers
Darwinizing the philosophy of music education.
Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2011.Educational philosophy generally and the Philosophy of Music Education in particular have
been slow to consider in any real depth the findings of those sciences most concerned with
explaining human nature, that is, the attributes (capacities, aptitudes, predilections, appetites)
we have in common because we share the same genome, much of which we also share with
other species. There are several such sciences which may collectively be called Darwinian
Science in that they all take as axiomatic Darwinâs explanation for how life evolves according
to the law of natural selection â a simple, mindless and purposeless algorithm that has played
out for over four billion years and which continues to do so, driving not only biological
evolution but, as this study argues, cultural evolution as well. Evolutionary Psychology
(including Biomusicology and Evolutionary Aesthetics), Cognitive Neuroscience and Gene-
Culture Coevolution Theory are the overlapping fields that this study draws from in developing
an understanding of the adapted mind useful for engaging with questions germane to the
Philosophy of Music Education, principally those concerning the nature and value of music and
how best it should feature in general education. These are questions that have not hitherto been
addressed from a Darwinian perspective. This study develops such a perspective and applies it
not only to questions around musicâs educational values and possibilities, but to more
encompassing philosophical questions, wherein the goals of music education are made
accountable in relation both to Deweyâs ideal of society as a function of education, and to an
ecozoic vision of a sustainable planetary habitat of interdependent and interconnected life
forms
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