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1.
Nucleic Acids Res ; 51(D1): D1353-D1359, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36399499

RESUMO

The Open Targets Platform (https://platform.opentargets.org/) is an open source resource to systematically assist drug target identification and prioritisation using publicly available data. Since our last update, we have reimagined, redesigned, and rebuilt the Platform in order to streamline data integration and harmonisation, expand the ways in which users can explore the data, and improve the user experience. The gene-disease causal evidence has been enhanced and expanded to better capture disease causality across rare, common, and somatic diseases. For target and drug annotations, we have incorporated new features that help assess target safety and tractability, including genetic constraint, PROTACtability assessments, and AlphaFold structure predictions. We have also introduced new machine learning applications for knowledge extraction from the published literature, clinical trial information, and drug labels. The new technologies and frameworks introduced since the last update will ease the introduction of new features and the creation of separate instances of the Platform adapted to user requirements. Our new Community forum, expanded training materials, and outreach programme support our users in a range of use cases.

2.
Nucleic Acids Res ; 49(D1): D1302-D1310, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33196847

RESUMO

The Open Targets Platform (https://www.targetvalidation.org/) provides users with a queryable knowledgebase and user interface to aid systematic target identification and prioritisation for drug discovery based upon underlying evidence. It is publicly available and the underlying code is open source. Since our last update two years ago, we have had 10 releases to maintain and continuously improve evidence for target-disease relationships from 20 different data sources. In addition, we have integrated new evidence from key datasets, including prioritised targets identified from genome-wide CRISPR knockout screens in 300 cancer models (Project Score), and GWAS/UK BioBank statistical genetic analysis evidence from the Open Targets Genetics Portal. We have evolved our evidence scoring framework to improve target identification. To aid the prioritisation of targets and inform on the potential impact of modulating a given target, we have added evaluation of post-marketing adverse drug reactions and new curated information on target tractability and safety. We have also developed the user interface and backend technologies to improve performance and usability. In this article, we describe the latest enhancements to the Platform, to address the fundamental challenge that developing effective and safe drugs is difficult and expensive.


Assuntos
Antineoplásicos/uso terapêutico , Drogas em Investigação/uso terapêutico , Bases de Conhecimento , Terapia de Alvo Molecular/métodos , Neoplasias/tratamento farmacológico , Software , Antineoplásicos/química , Bases de Dados Factuais , Conjuntos de Dados como Assunto , Descoberta de Drogas/métodos , Drogas em Investigação/química , Humanos , Internet , Neoplasias/classificação , Neoplasias/genética , Neoplasias/patologia
3.
Nucleic Acids Res ; 49(D1): D1311-D1320, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33045747

RESUMO

Open Targets Genetics (https://genetics.opentargets.org) is an open-access integrative resource that aggregates human GWAS and functional genomics data including gene expression, protein abundance, chromatin interaction and conformation data from a wide range of cell types and tissues to make robust connections between GWAS-associated loci, variants and likely causal genes. This enables systematic identification and prioritisation of likely causal variants and genes across all published trait-associated loci. In this paper, we describe the public resources we aggregate, the technology and analyses we use, and the functionality that the portal offers. Open Targets Genetics can be searched by variant, gene or study/phenotype. It offers tools that enable users to prioritise causal variants and genes at disease-associated loci and access systematic cross-disease and disease-molecular trait colocalization analysis across 92 cell types and tissues including the eQTL Catalogue. Data visualizations such as Manhattan-like plots, regional plots, credible sets overlap between studies and PheWAS plots enable users to explore GWAS signals in depth. The integrated data is made available through the web portal, for bulk download and via a GraphQL API, and the software is open source. Applications of this integrated data include identification of novel targets for drug discovery and drug repurposing.


Assuntos
Bases de Dados Genéticas , Genoma Humano , Doenças Inflamatórias Intestinais/genética , Terapia de Alvo Molecular/métodos , Locos de Características Quantitativas , Software , Cromatina/química , Cromatina/metabolismo , Conjuntos de Dados como Assunto , Descoberta de Drogas/métodos , Reposicionamento de Medicamentos/métodos , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/patologia , Internet , Fenótipo , Característica Quantitativa Herdável
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