Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 9 de 9
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
Cell ; 165(3): 742-53, 2016 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-27040499

RESUMO

RNA transcripts are bound and regulated by RNA-binding proteins (RBPs). Current methods for identifying in vivo targets of an RBP are imperfect and not amenable to examining small numbers of cells. To address these issues, we developed TRIBE (targets of RNA-binding proteins identified by editing), a technique that couples an RBP to the catalytic domain of the Drosophila RNA-editing enzyme ADAR and expresses the fusion protein in vivo. RBP targets are marked with novel RNA editing events and identified by sequencing RNA. We have used TRIBE to identify the targets of three RBPs (Hrp48, dFMR1, and NonA). TRIBE compares favorably to other methods, including CLIP, and we have identified RBP targets from as little as 150 specific fly neurons. TRIBE can be performed without an antibody and in small numbers of specific cells.


Assuntos
Adenosina Desaminase/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/enzimologia , Técnicas Genéticas , Edição de RNA , Regiões 3' não Traduzidas , Animais , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Proteínas de Ligação a RNA
2.
Nucleic Acids Res ; 49(D1): D884-D891, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33137190

RESUMO

The Ensembl project (https://www.ensembl.org) annotates genomes and disseminates genomic data for vertebrate species. We create detailed and comprehensive annotation of gene structures, regulatory elements and variants, and enable comparative genomics by inferring the evolutionary history of genes and genomes. Our integrated genomic data are made available in a variety of ways, including genome browsers, search interfaces, specialist tools such as the Ensembl Variant Effect Predictor, download files and programmatic interfaces. Here, we present recent Ensembl developments including two new website portals. Ensembl Rapid Release (http://rapid.ensembl.org) is designed to provide core tools and services for genomes as soon as possible and has been deployed to support large biodiversity sequencing projects. Our SARS-CoV-2 genome browser (https://covid-19.ensembl.org) integrates our own annotation with publicly available genomic data from numerous sources to facilitate the use of genomics in the international scientific response to the COVID-19 pandemic. We also report on other updates to our annotation resources, tools and services. All Ensembl data and software are freely available without restriction.


Assuntos
Biologia Computacional/métodos , Bases de Dados de Ácidos Nucleicos , Genômica/métodos , SARS-CoV-2/genética , Vertebrados/genética , Animais , COVID-19/epidemiologia , COVID-19/virologia , Humanos , Internet , Anotação de Sequência Molecular/métodos , Pandemias , Vertebrados/classificação
3.
Nucleic Acids Res ; 47(D1): D745-D751, 2019 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-30407521

RESUMO

The Ensembl project (https://www.ensembl.org) makes key genomic data sets available to the entire scientific community without restrictions. Ensembl seeks to be a fundamental resource driving scientific progress by creating, maintaining and updating reference genome annotation and comparative genomics resources. This year we describe our new and expanded gene, variant and comparative annotation capabilities, which led to a 50% increase in the number of vertebrate genomes we support. We have also doubled the number of available human variants and added regulatory regions for many mouse cell types and developmental stages. Our data sets and tools are available via the Ensembl website as well as a through a RESTful webservice, Perl application programming interface and as data files for download.


Assuntos
Bases de Dados Genéticas , Genoma/genética , Genômica , Vertebrados/genética , Animais , Biologia Computacional/tendências , Humanos , Camundongos , Anotação de Sequência Molecular , Software
5.
Genet Med ; 21(4): 837-849, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30206421

RESUMO

PURPOSE: Variants in IQSEC2, escaping X inactivation, cause X-linked intellectual disability with frequent epilepsy in males and females. We aimed to investigate sex-specific differences. METHODS: We collected the data of 37 unpublished patients (18 males and 19 females) with IQSEC2 pathogenic variants and 5 individuals with variants of unknown significance and reviewed published variants. We compared variant types and phenotypes in males and females and performed an analysis of IQSEC2 isoforms. RESULTS: IQSEC2 pathogenic variants mainly led to premature truncation and were scattered throughout the longest brain-specific isoform, encoding the synaptic IQSEC2/BRAG1 protein. Variants occurred de novo in females but were either de novo (2/3) or inherited (1/3) in males, with missense variants being predominantly inherited. Developmental delay and intellectual disability were overall more severe in males than in females. Likewise, seizures were more frequently observed and intractable, and started earlier in males than in females. No correlation was observed between the age at seizure onset and severity of intellectual disability or resistance to antiepileptic treatments. CONCLUSION: This study provides a comprehensive overview of IQSEC2-related encephalopathy in males and females, and suggests that an accurate dosage of IQSEC2 at the synapse is crucial during normal brain development.


Assuntos
Encefalopatias/genética , Fatores de Troca do Nucleotídeo Guanina/genética , Deficiência Intelectual/genética , Convulsões/genética , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Encefalopatias/epidemiologia , Encefalopatias/fisiopatologia , Feminino , Humanos , Lactente , Recém-Nascido , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/fisiopatologia , Masculino , Mutação , Linhagem , Fenótipo , Isoformas de Proteínas/genética , Convulsões/epidemiologia , Convulsões/fisiopatologia , Caracteres Sexuais
7.
Cell Metab ; 35(4): 695-710.e6, 2023 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-36963395

RESUMO

Associations between human genetic variation and clinical phenotypes have become a foundation of biomedical research. Most repositories of these data seek to be disease-agnostic and therefore lack disease-focused views. The Type 2 Diabetes Knowledge Portal (T2DKP) is a public resource of genetic datasets and genomic annotations dedicated to type 2 diabetes (T2D) and related traits. Here, we seek to make the T2DKP more accessible to prospective users and more useful to existing users. First, we evaluate the T2DKP's comprehensiveness by comparing its datasets with those of other repositories. Second, we describe how researchers unfamiliar with human genetic data can begin using and correctly interpreting them via the T2DKP. Third, we describe how existing users can extend their current workflows to use the full suite of tools offered by the T2DKP. We finally discuss the lessons offered by the T2DKP toward the goal of democratizing access to complex disease genetic results.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/genética , Acesso à Informação , Estudos Prospectivos , Genômica/métodos , Fenótipo
8.
Mol Genet Genomic Med ; 9(12): e1786, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34435752

RESUMO

BACKGROUND: Variant interpretation is dependent on transcript annotation and remains time consuming and challenging. There are major obstacles for historical data reuse and for interpretation of new variants. First, both RefSeq and Ensembl/GENCODE produce transcript sets in common use, but there is currently no easy way to translate between the two. Second, the resources often used for variant interpretation (e.g. ClinVar, gnomAD, UniProt) do not use the same transcript set, nor default transcript or protein sequence. METHOD: Ensembl ran a survey in 2018 to sample attitudes to choosing one default transcript per locus, and to gather data on reference sequences used by the scientific community. This was publicised on the Ensembl and UCSC genome browsers, by email and on social media. RESULTS: The survey had 788 responses from 32 different countries, the results of which we report here. CONCLUSIONS: We present our roadmap to create an effective default set of transcripts for resources, and for reporting interpretation of clinical variants.


Assuntos
Biomarcadores , Biologia Computacional , Genômica , RNA Mensageiro/genética , Animais , Biologia Computacional/métodos , Bases de Dados Genéticas , Genômica/métodos , Humanos , Software , Navegador
9.
Genome Biol ; 19(1): 21, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29448949

RESUMO

The accurate description of ancestry is essential to interpret, access, and integrate human genomics data, and to ensure that these benefit individuals from all ancestral backgrounds. However, there are no established guidelines for the representation of ancestry information. Here we describe a framework for the accurate and standardized description of sample ancestry, and validate it by application to the NHGRI-EBI GWAS Catalog. We confirm known biases and gaps in diversity, and find that African and Hispanic or Latin American ancestry populations contribute a disproportionately high number of associations. It is our hope that widespread adoption of this framework will lead to improved analysis, interpretation, and integration of human genomics data.


Assuntos
Estudo de Associação Genômica Ampla/normas , Genômica/normas , Variação Genética , Humanos , Grupos Raciais
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA