1,721,107 research outputs found
Multilayer modelling of the human transcriptome and biological mechanisms of complex diseases and traits
Full text linkAbstract: Here, we performed a comprehensive intra-tissue and inter-tissue multilayer network analysis of the human transcriptome. We generated an atlas of communities in gene co-expression networks in 49 tissues (GTEx v8), evaluated their tissue specificity, and investigated their methodological implications. UMAP embeddings of gene expression from the communities (representing nearly 18% of all genes) robustly identified biologically-meaningful clusters. Notably, new gene expression data can be embedded into our algorithmically derived models to accelerate discoveries in high-dimensional molecular datasets and downstream diagnostic or prognostic applications. We demonstrate the generalisability of our approach through systematic testing in external genomic and transcriptomic datasets. Methodologically, prioritisation of the communities in a transcriptome-wide association study of the biomarker C-reactive protein (CRP) in 361,194 individuals in the UK Biobank identified genetically-determined expression changes associated with CRP and led to considerably improved performance. Furthermore, a deep learning framework applied to the communities in nearly 11,000 tumors profiled by The Cancer Genome Atlas across 33 different cancer types learned biologically-meaningful latent spaces, representing metastasis (p < 2.2 × 10−16) and stemness (p < 2.2 × 10−16). Our study provides a rich genomic resource to catalyse research into inter-tissue regulatory mechanisms, and their downstream consequences on human disease
Modelling of the transcriptome using networks
No full textThis repository contains all the code necessary to run and further extend the experiments presented in our paper. Please cite:
Azevedo, Tiago, Dimitri, Giovanna Maria, Lio, Pietro, & Gamazon, Eric R. (2020) "Multilayer modelling and analysis of the human transcriptome." bioRxiv. https://www.biorxiv.org/content/10.1101/2020.05.21.109082v4
Azevedo, Tiago, Dimitri, Giovanna Maria, Lio, Pietro, & Gamazon, Eric R. (2020, May 25). Modelling of the transcriptome using networks (Version 1). Zenodo. http://doi.org/10.5281/zenodo.3842659
Abstract
In the present work, we performed a comprehensive intra-tissue and inter-tissue network analysis of the human transcriptome. We generated an atlas of communities in co-expression networks in each of 49 tissues and evaluated their tissue specificity. UMAP embeddings of gene expression from the identified communities recovered biologically meaningful tissue clusters, based on tissue organ membership or known shared function. We developed an approach to quantify the conservation of global structure and estimate the sampling distribution of the distance between tissue clusters via bootstrapped manifolds. We found not only preserved local structure among clearly related tissues (e.g., the 13 brain regions) but also a strong correlation between the clustering of these related tissues relative to the remaining ones. Interestingly, brain tissues showed significantly higher variability in community size than non-brain (p = 1.55x10-4). We identified communities that capture some of our current knowledge about biological processes, but most are likely to encode novel and previously inaccessible functional information. For example, we found a 17-member community present across all of the brain regions, which shows significant enrichment for the nonsense-mediated decay pathway (adjusted p = 1.01x10-37). We also constructed multiplex architectures to gain insights into tissue-to-tissue mechanisms for regulation of communities in the transcriptome, including communities that are likely to play a functional role throughout the central nervous system (CNS) and communities that may participate in the interaction between the CNS and the enteric nervous system. Notably, new gene expression data can be embedded into our models to accelerate discoveries in high-dimensional molecular datasets. Our study provides a rich resource of co-expression networks, communities, multiplex architectures, and enriched pathways in a broad collection of tissues, to catalyse research into inter-tissue regulatory mechanisms and enable insights into their downstream phenotypic consequences
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Full text linkWe 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
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