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The development of ASTRA, an automatized workflow for allele specific expression and chromatin accessibility analysis from high-throughput sequencing data.
No full textGli organismi diploidi sono provvisti di due copie quasi identiche per ogni gene e, generalmente, entrambi gli alleli sono trascritti allo stesso livello. Tuttavia, sono presenti alcune eccezioni: i geni del cromosoma X, soggetti a meccanismi di di compensazione del dosaggio, e i geni dell’imprinting, espressi da uno specifico allele parentale. Recentemente è stato dimostrato che anche numerosi geni autosomici sono espressi in modo monoallelico. Questo comportamento, come mostrano recenti pubblicazioni, è transitorio durante le fasi di sviluppo e, inoltre, risulta essere specifico per il tipo di tessuto e per il gruppo cellulare.
Questa evidenza ci suggerisce l'importanza di ripensare gli studi di espressione in termini di espressione allele specifica. Ad esempio, molte varianti genetiche che influenzano i fenotipi e le malattie umane sono eterozigoti e lo studio dell'espressione allele specifica potrebbe districare il significato funzionale di questi siti e fornire approfondimenti in termini di correlazioni genotipo-fenotipo.
Inoltre, si ritiene sempre più che i fattori epigenetici svolgano un ruolo anche sull'espressione allelica differenziale. In particolare, è stato dimostrato che la specificità allelica sia dell'espressione (ASE) che dell'accessibilità della cromatina (ASA) possono avere un'importante influenza congiunta sia in stati fisiologici che in quelli patologici.
Tuttavia, data l'elevata eterogeneità degli approcci analitici disponibili, la comunità scientifica trarrebbe vantaggio da una pipeline bioinformatica integrata che consenta l'analisi congiunta ASA e ASE.
Abbiamo pertanto sviluppato un approccio computazionale denominato ASTRA (Allelic Specific Transcriptional Regulation Analysis), organizzato come flusso di lavoro automatizzato e riproducibile. ASTRA consente l'analisi integrata dell’espressione e accessibilità allele-specifica a partire da dati grezzi di sequenziamento RNA e/o di accessibilità della cromatina, in bulk o a singola cellula.
Per poter ottenere uno strumento raffinato, applicabile a diversi contesti e di facile utilizzo, abbiamo applicato e testato ASTRA a diversi casi studio dimostrandone l’efficacia e l’utilità. ASTRA si propone quindi come uno strumento per fornire un'istantanea del panorama trascrizionale dell'intero genoma e per migliorare la nostra comprensione dei fattori determinanti dell'espressione allelica differenziale.Diploid organisms are provided with nearly identical pairs of each gene, and generally, both alleles are transcribed at the same level. However, there are some exceptions: genes on the X chromosome, which are subject to mechanisms for dosage compensation, and imprinted genes, which are expressed from a specific parental allele. Recently, it has been demonstrated that numerous autosomal genes are also expressed in a monoallelic manner. This behavior, as shown by recent publications, is transient during developmental stages and is tissue and cell type specific.
This evidence suggests the importance of rethinking expression studies in terms of allele-specific expression. For example, many genetic variants that influence human phenotypes and diseases are heterozygous, and studying allele-specific expression could unravel the functional significance of these sites and provide insights into genotype-phenotype correlations.
Moreover, it is increasingly believed that epigenetic factors play a role in allelic differential expression. Specifically, it has been shown that allele-specific expression (ASE) and chromatin accessibility (ASA) can have a significant combined influence in both physiological and pathological states.
However, given the high heterogeneity of available analytical approaches, the scientific community would benefit from an integrated bioinformatics pipeline that allows for the joint analysis of ASA and ASE.
We have therefore developed a computational approach called ASTRA (Allele Specific Transcriptional Regulation Analysis), organized as an automated and reproducible workflow. ASTRA enables the integrated analysis of allele-specific expression and chromatin accessibility from raw RNA sequencing and/or chromatin accessibility data, in bulk or single-cell contexts.
To obtain a refined tool applicable to various contexts and easy to use, we applied and tested ASTRA on several case studies, demonstrating its efficacy and utility. ASTRA thus proposes itself as a tool to provide a snapshot of the transcriptional landscape of the entire genome and to improve our understanding of the factors determining allelic differential expression
Allele-specific expression analysis: pipelines, applications, challenges, and unmet needs
No full textIn diploid organisms, genes typically exhibit balanced expression of maternal and paternal alleles. However, exceptions exist, such as autosomal genes with allele-specific expression, where genetic and epigenetic variations can lead to the exclusive or preferential expression of a particular allele. In this context, allele-specific expression analysis serves as a powerful tool for understanding gene regulation, with significant functional and clinical implications.
Despite their increasing importance, current analysis pipelines face notable limitations including a lack of end-to-end solutions, restricted options for multi-omics integration, and insufficient support for single-cell sequencing technologies.
This review critically assesses 26 cutting-edge pipelines for allele-specific expression analysis, focusing on their input requirements, capabilities, and applications in the field. Pipelines are categorized based on their ability to handle various data types, support haplotype phasing, employ statistical approaches, and provide graphical outputs. Most pipelines fail to automate preprocessing, integrate multi-omic data, and support high-throughput single-cell sequencing. Future advancements should prioritize the development of automated multi-omic workflows, implementing visualization options, and enhancing compatibility with single-cell technologies. By addressing these gaps, next-generation allele-specific expression pipelines will offer insights into the mechanisms of allele-specific expression regulation, thereby advancing our understanding of its biological and clinical significance
Protocol for generation of a time-resolved cellular interactome during tissue remodeling in adult mice
No full textEfficient skeletal muscle regeneration necessitates fine-tuned coordination among multiple cell types through an intricate network of intercellular communication. We present a protocol for generation of a time -resolved cellular interactome during tissue remodeling. We describe steps for isolating distinct cell populations from skeletal muscle of adult mice after acute damage and extracting RNA from purified cells prior to the generation of RNA sequencing data. We then detail procedures for generating and deciphering a time- and lineageresolved model of intercellular crosstalk. For complete details on the use and execution of this protocol, please refer to Groppa et al. (2023)
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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