RESUMEN
Curated scientific databases catalogue and amplify research findings to maximize their reach. Authors should write their papers with this in mind, ensuring that data are accurate, easy to extract, and presented in standardized formats.
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Escritura , Bases de Datos FactualesRESUMEN
The Catalogue Of Somatic Mutations In Cancer (COSMIC), https://cancer.sanger.ac.uk/cosmic, is an expert-curated knowledgebase providing data on somatic variants in cancer, supported by a comprehensive suite of tools for interpreting genomic data, discerning the impact of somatic alterations on disease, and facilitating translational research. The catalogue is accessed and used by thousands of cancer researchers and clinicians daily, allowing them to quickly access information from an immense pool of data curated from over 29 thousand scientific publications and large studies. Within the last 4 years, COSMIC has substantially expanded its utility by adding new resources: the Mutational Signatures catalogue, the Cancer Mutation Census, and Actionability. To improve data accessibility and interoperability, somatic variants have received stable genomic identifiers that are associated with their genomic coordinates in GRCh37 and GRCh38, and new export files with reduced data redundancy have been made available for download.
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Bases de Datos Genéticas , Genómica , Neoplasias , Humanos , Bases de Datos Factuales , Bases del Conocimiento , Mutación , Neoplasias/genética , Bases de Datos Genéticas/tendencias , InternetRESUMEN
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.
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Antineoplásicos/uso terapéutico , Drogas en Investigación/uso terapéutico , Bases del Conocimiento , Terapia Molecular Dirigida/métodos , Neoplasias/tratamiento farmacológico , Programas Informáticos , Antineoplásicos/química , Bases de Datos Factuales , Conjuntos de Datos como Asunto , Descubrimiento de Drogas/métodos , Drogas en Investigación/química , Humanos , Internet , Neoplasias/clasificación , Neoplasias/genética , Neoplasias/patologíaRESUMEN
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.
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Bases de Datos Genéticas , Genoma Humano , Enfermedades Inflamatorias del Intestino/genética , Terapia Molecular Dirigida/métodos , Sitios de Carácter Cuantitativo , Programas Informáticos , Cromatina/química , Cromatina/metabolismo , Conjuntos de Datos como Asunto , Descubrimiento de Drogas/métodos , Reposicionamiento de Medicamentos/métodos , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/metabolismo , Enfermedades Inflamatorias del Intestino/patología , Internet , Fenotipo , Carácter Cuantitativo HeredableRESUMEN
Everything we do today is becoming more and more reliant on the use of computers. The field of biology is no exception; but most biologists receive little or no formal preparation for the increasingly computational aspects of their discipline. In consequence, informal training courses are often needed to plug the gaps; and the demand for such training is growing worldwide. To meet this demand, some training programs are being expanded, and new ones are being developed. Key to both scenarios is the creation of new course materials. Rather than starting from scratch, however, it's sometimes possible to repurpose materials that already exist. Yet finding suitable materials online can be difficult: They're often widely scattered across the internet or hidden in their home institutions, with no systematic way to find them. This is a common problem for all digital objects. The scientific community has attempted to address this issue by developing a set of rules (which have been called the Findable, Accessible, Interoperable and Reusable [FAIR] principles) to make such objects more findable and reusable. Here, we show how to apply these rules to help make training materials easier to find, (re)use, and adapt, for the benefit of all.
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Instrucción por Computador/normas , Guías como Asunto , Biología/educación , Biología Computacional , Humanos , Almacenamiento y Recuperación de la InformaciónRESUMEN
The Open Targets Platform integrates evidence from genetics, genomics, transcriptomics, drugs, animal models and scientific literature to score and rank target-disease associations for drug target identification. The associations are displayed in an intuitive user interface (https://www.targetvalidation.org), and are available through a REST-API (https://api.opentargets.io/v3/platform/docs/swagger-ui) and a bulk download (https://www.targetvalidation.org/downloads/data). In addition to target-disease associations, we also aggregate and display data at the target and disease levels to aid target prioritisation. Since our first publication two years ago, we have made eight releases, added new data sources for target-disease associations, started including causal genetic variants from non genome-wide targeted arrays, added new target and disease annotations, launched new visualisations and improved existing ones and released a new web tool for batch search of up to 200 targets. We have a new URL for the Open Targets Platform REST-API, new REST endpoints and also removed the need for authorisation for API fair use. Here, we present the latest developments of the Open Targets Platform, expanding the evidence and target-disease associations with new and improved data sources, refining data quality, enhancing website usability, and increasing our user base with our training workshops, user support, social media and bioinformatics forum engagement.
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Biología Computacional/métodos , Bases de Datos Genéticas , Genómica/métodos , Almacenamiento y Recuperación de la Información/métodos , Terapia Molecular Dirigida/métodos , Biología Computacional/tendencias , Perfilación de la Expresión Génica/métodos , Genómica/tendencias , Humanos , Almacenamiento y Recuperación de la Información/tendencias , Internet , Reproducibilidad de los Resultados , Programas InformáticosRESUMEN
Ensembl Genomes (http://www.ensemblgenomes.org) is an integrating resource for genome-scale data from non-vertebrate species, complementing the resources for vertebrate genomics developed in the Ensembl project (http://www.ensembl.org). Together, the two resources provide a consistent set of programmatic and interactive interfaces to a rich range of data including genome sequence, gene models, transcript sequence, genetic variation, and comparative analysis. This paper provides an update to the previous publications about the resource, with a focus on recent developments and expansions. These include the incorporation of almost 20 000 additional genome sequences and over 35 000 tracks of RNA-Seq data, which have been aligned to genomic sequence and made available for visualization. Other advances since 2015 include the release of the database in Resource Description Framework (RDF) format, a large increase in community-derived curation, a new high-performance protein sequence search, additional cross-references, improved annotation of non-protein-coding genes, and the launch of pre-release and archival sites. Collectively, these changes are part of a continuing response to the increasing quantity of publicly-available genome-scale data, and the consequent need to archive, integrate, annotate and disseminate these using automated, scalable methods.
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Archaea/genética , Bacterias/genética , Bases de Datos Genéticas , Bases de Datos de Proteínas , Eucariontes/genética , Genómica , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Minería de Datos , Predicción , Genoma , Anotación de Secuencia Molecular , ARN/genética , Interfaz Usuario-ComputadorRESUMEN
We have generated an improved assembly and gene annotation of the pig X Chromosome, and a first draft assembly of the pig Y Chromosome, by sequencing BAC and fosmid clones from Duroc animals and incorporating information from optical mapping and fiber-FISH. The X Chromosome carries 1033 annotated genes, 690 of which are protein coding. Gene order closely matches that found in primates (including humans) and carnivores (including cats and dogs), which is inferred to be ancestral. Nevertheless, several protein-coding genes present on the human X Chromosome were absent from the pig, and 38 pig-specific X-chromosomal genes were annotated, 22 of which were olfactory receptors. The pig Y-specific Chromosome sequence generated here comprises 30 megabases (Mb). A 15-Mb subset of this sequence was assembled, revealing two clusters of male-specific low copy number genes, separated by an ampliconic region including the HSFY gene family, which together make up most of the short arm. Both clusters contain palindromes with high sequence identity, presumably maintained by gene conversion. Many of the ancestral X-related genes previously reported in at least one mammalian Y Chromosome are represented either as active genes or partial sequences. This sequencing project has allowed us to identify genes--both single copy and amplified--on the pig Y Chromosome, to compare the pig X and Y Chromosomes for homologous sequences, and thereby to reveal mechanisms underlying pig X and Y Chromosome evolution.
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Cromosomas de los Mamíferos/genética , Evolución Molecular , Porcinos/genética , Cromosoma X/genética , Cromosoma Y/genética , Animales , Secuencia de Bases , Gatos/genética , Perros/genética , Femenino , Conversión Génica , Expresión Génica , Biblioteca de Genes , Orden Génico , Humanos , Masculino , Datos de Secuencia Molecular , Alineación de Secuencia , Análisis de Secuencia de ADNRESUMEN
Ensembl (www.ensembl.org) is a database and genome browser for enabling research on vertebrate genomes. We import, analyse, curate and integrate a diverse collection of large-scale reference data to create a more comprehensive view of genome biology than would be possible from any individual dataset. Our extensive data resources include evidence-based gene and regulatory region annotation, genome variation and gene trees. An accompanying suite of tools, infrastructure and programmatic access methods ensure uniform data analysis and distribution for all supported species. Together, these provide a comprehensive solution for large-scale and targeted genomics applications alike. Among many other developments over the past year, we have improved our resources for gene regulation and comparative genomics, and added CRISPR/Cas9 target sites. We released new browser functionality and tools, including improved filtering and prioritization of genome variation, Manhattan plot visualization for linkage disequilibrium and eQTL data, and an ontology search for phenotypes, traits and disease. We have also enhanced data discovery and access with a track hub registry and a selection of new REST end points. All Ensembl data are freely released to the scientific community and our source code is available via the open source Apache 2.0 license.
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Biología Computacional/métodos , Bases de Datos Genéticas , Genómica/métodos , Motor de Búsqueda , Programas Informáticos , Navegador Web , Animales , Minería de Datos , Evolución Molecular , Regulación de la Expresión Génica , Variación Genética , Genoma Humano , Humanos , Anotación de Secuencia Molecular , Especificidad de la Especie , VertebradosRESUMEN
We have designed and developed a data integration and visualization platform that provides evidence about the association of known and potential drug targets with diseases. The platform is designed to support identification and prioritization of biological targets for follow-up. Each drug target is linked to a disease using integrated genome-wide data from a broad range of data sources. The platform provides either a target-centric workflow to identify diseases that may be associated with a specific target, or a disease-centric workflow to identify targets that may be associated with a specific disease. Users can easily transition between these target- and disease-centric workflows. The Open Targets Validation Platform is accessible at https://www.targetvalidation.org.
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Biología Computacional/métodos , Terapia Molecular Dirigida , Motor de Búsqueda , Programas Informáticos , Bases de Datos Factuales , Humanos , Terapia Molecular Dirigida/métodos , Reproducibilidad de los Resultados , Navegador Web , Flujo de TrabajoRESUMEN
For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars â¼1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model.
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Genoma/genética , Filogenia , Sus scrofa/clasificación , Sus scrofa/genética , Animales , Demografía , Modelos Animales , Datos de Secuencia Molecular , Dinámica PoblacionalRESUMEN
Ensembl Genomes (http://www.ensemblgenomes.org) is an integrating resource for genome-scale data from non-vertebrate species, complementing the resources for vertebrate genomics developed in the context of the Ensembl project (http://www.ensembl.org). Together, the two resources provide a consistent set of programmatic and interactive interfaces to a rich range of data including reference sequence, gene models, transcriptional data, genetic variation and comparative analysis. This paper provides an update to the previous publications about the resource, with a focus on recent developments. These include the development of new analyses and views to represent polyploid genomes (of which bread wheat is the primary exemplar); and the continued up-scaling of the resource, which now includes over 23 000 bacterial genomes, 400 fungal genomes and 100 protist genomes, in addition to 55 genomes from invertebrate metazoa and 39 genomes from plants. This dramatic increase in the number of included genomes is one part of a broader effort to automate the integration of archival data (genome sequence, but also associated RNA sequence data and variant calls) within the context of reference genomes and make it available through the Ensembl user interfaces.
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Bases de Datos Genéticas , Genoma Bacteriano , Genoma Fúngico , Genoma de Planta , Invertebrados/genética , Animales , Diploidia , Eucariontes/genética , Variación Genética , Genoma , Poliploidía , Alineación de SecuenciaRESUMEN
The Ensembl project (http://www.ensembl.org) is a system for genome annotation, analysis, storage and dissemination designed to facilitate the access of genomic annotation from chordates and key model organisms. It provides access to data from 87 species across our main and early access Pre! websites. This year we introduced three newly annotated species and released numerous updates across our supported species with a concentration on data for the latest genome assemblies of human, mouse, zebrafish and rat. We also provided two data updates for the previous human assembly, GRCh37, through a dedicated website (http://grch37.ensembl.org). Our tools, in particular the VEP, have been improved significantly through integration of additional third party data. REST is now capable of larger-scale analysis and our regulatory data BioMart can deliver faster results. The website is now capable of displaying long-range interactions such as those found in cis-regulated datasets. Finally we have launched a website optimized for mobile devices providing views of genes, variants and phenotypes. Our data is made available without restriction and all code is available from our GitHub organization site (http://github.com/Ensembl) under an Apache 2.0 license.
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Bases de Datos Genéticas , Genómica , Anotación de Secuencia Molecular , Animales , Genes , Variación Genética , Humanos , Internet , Ratones , Proteínas/genética , Ratas , Secuencias Reguladoras de Ácidos Nucleicos , Programas InformáticosRESUMEN
Ensembl (http://www.ensembl.org) is a genomic interpretation system providing the most up-to-date annotations, querying tools and access methods for chordates and key model organisms. This year we released updated annotation (gene models, comparative genomics, regulatory regions and variation) on the new human assembly, GRCh38, although we continue to support researchers using the GRCh37.p13 assembly through a dedicated site (http://grch37.ensembl.org). Our Regulatory Build has been revamped to identify regulatory regions of interest and to efficiently highlight their activity across disparate epigenetic data sets. A number of new interfaces allow users to perform large-scale comparisons of their data against our annotations. The REST server (http://rest.ensembl.org), which allows programs written in any language to query our databases, has moved to a full service alongside our upgraded website tools. Our online Variant Effect Predictor tool has been updated to process more variants and calculate summary statistics. Lastly, the WiggleTools package enables users to summarize large collections of data sets and view them as single tracks in Ensembl. The Ensembl code base itself is more accessible: it is now hosted on our GitHub organization page (https://github.com/Ensembl) under an Apache 2.0 open source license.
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Bases de Datos de Ácidos Nucleicos , Genómica , Animales , Epigénesis Genética , Variación Genética , Genoma Humano , Humanos , Internet , Ratones , Anotación de Secuencia Molecular , Secuencias Reguladoras de Ácidos Nucleicos , Programas InformáticosRESUMEN
Ensembl (http://www.ensembl.org) creates tools and data resources to facilitate genomic analysis in chordate species with an emphasis on human, major vertebrate model organisms and farm animals. Over the past year we have increased the number of species that we support to 77 and expanded our genome browser with a new scrollable overview and improved variation and phenotype views. We also report updates to our core datasets and improvements to our gene homology relationships from the addition of new species. Our REST service has been extended with additional support for comparative genomics and ontology information. Finally, we provide updated information about our methods for data access and resources for user training.
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Bases de Datos Genéticas , Genómica , Animales , Cordados/genética , Variación Genética , Humanos , Internet , Ratones , Anotación de Secuencia Molecular , Fenotipo , RatasRESUMEN
The Ensembl project (http://www.ensembl.org) provides genome information for sequenced chordate genomes with a particular focus on human, mouse, zebrafish and rat. Our resources include evidenced-based gene sets for all supported species; large-scale whole genome multiple species alignments across vertebrates and clade-specific alignments for eutherian mammals, primates, birds and fish; variation data resources for 17 species and regulation annotations based on ENCODE and other data sets. Ensembl data are accessible through the genome browser at http://www.ensembl.org and through other tools and programmatic interfaces.
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Bases de Datos Genéticas , Genómica , Animales , Regulación de la Expresión Génica , Variación Genética , Humanos , Internet , Ratones , Anotación de Secuencia Molecular , Ratas , Programas Informáticos , Pez Cebra/genéticaRESUMEN
The male-specific region of the human Y chromosome (MSY) contains eight large inverted repeats (palindromes), in which high-sequence similarity between repeat arms is maintained by gene conversion. These palindromes also harbor microsatellites, considered to evolve via a stepwise mutation model (SMM). Here, we ask whether gene conversion between palindrome microsatellites contributes to their mutational dynamics. First, we study the duplicated tetranucleotide microsatellite DYS385a,b lying in palindrome P4. We show, by comparing observed data with simulated data under a SMM within haplogroups, that observed heteroallelic combinations in which the modal repeat number difference between copies was large, can give rise to homoallelic combinations with zero-repeats difference, equivalent to many single-step mutations. These are unlikely to be generated under a strict SMM, suggesting the action of gene conversion. Second, we show that the intercopy repeat number difference for a large set of duplicated microsatellites in all palindromes in the MSY reference sequence is significantly reduced compared with that for nonpalindrome-duplicated microsatellites, suggesting that the former are characterized by unusual evolutionary dynamics. These observations indicate that gene conversion violates the SMM for microsatellites in palindromes, homogenizing copies within individual Y chromosomes, but increasing overall haplotype diversity among chromosomes within related groups.
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Conversión Génica , Secuencias Invertidas Repetidas/genética , Repeticiones de Microsatélite/genética , Mutación , Cromosomas Humanos Y/genética , Humanos , Modelos GenéticosAsunto(s)
Biología Computacional/métodos , Bases de Datos Genéticas/tendencias , Almacenamiento y Recuperación de la Información/métodos , Disciplinas de las Ciencias Biológicas , Bases de Datos Factuales/estadística & datos numéricos , Bases de Datos Factuales/tendencias , Bases de Datos Genéticas/estadística & datos numéricos , Genómica , Humanos , Programas Informáticos , Interfaz Usuario-ComputadorRESUMEN
The Ensembl project (http://www.ensembl.org) provides genome resources for chordate genomes with a particular focus on human genome data as well as data for key model organisms such as mouse, rat and zebrafish. Five additional species were added in the last year including gibbon (Nomascus leucogenys) and Tasmanian devil (Sarcophilus harrisii) bringing the total number of supported species to 61 as of Ensembl release 64 (September 2011). Of these, 55 species appear on the main Ensembl website and six species are provided on the Ensembl preview site (Pre!Ensembl; http://pre.ensembl.org) with preliminary support. The past year has also seen improvements across the project.