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1.
Nucleic Acids Res ; 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34788843

RESUMO

The Reactome Knowledgebase (https://reactome.org), an Elixir core resource, provides manually curated molecular details across a broad range of physiological and pathological biological processes in humans, including both hereditary and acquired disease processes. The processes are annotated as an ordered network of molecular transformations in a single consistent data model. Reactome thus functions both as a digital archive of manually curated human biological processes and as a tool for discovering functional relationships in data such as gene expression profiles or somatic mutation catalogs from tumor cells. Recent curation work has expanded our annotations of normal and disease-associated signaling processes and of the drugs that target them, in particular infections caused by the SARS-CoV-1 and SARS-CoV-2 coronaviruses and the host response to infection. New tools support better simultaneous analysis of high-throughput data from multiple sources and the placement of understudied ('dark') proteins from analyzed datasets in the context of Reactome's manually curated pathways.

2.
Nucleic Acids Res ; 48(D1): D498-D503, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31691815

RESUMO

The Reactome Knowledgebase (https://reactome.org) provides molecular details of signal transduction, transport, DNA replication, metabolism and other cellular processes as an ordered network of molecular transformations in a single consistent data model, an extended version of a classic metabolic map. Reactome functions both as an archive of biological processes and as a tool for discovering functional relationships in data such as gene expression profiles or somatic mutation catalogs from tumor cells. To extend our ability to annotate human disease processes, we have implemented a new drug class and have used it initially to annotate drugs relevant to cardiovascular disease. Our annotation model depends on external domain experts to identify new areas for annotation and to review new content. New web pages facilitate recruitment of community experts and allow those who have contributed to Reactome to identify their contributions and link them to their ORCID records. To improve visualization of our content, we have implemented a new tool to automatically lay out the components of individual reactions with multiple options for downloading the reaction diagrams and associated data, and a new display of our event hierarchy that will facilitate visual interpretation of pathway analysis results.


Assuntos
Bases de Dados de Compostos Químicos , Bases de Dados de Produtos Farmacêuticos , Bases de Conhecimento , Software , Genoma Humano , Humanos , Redes e Vias Metabólicas , Mapas de Interação de Proteínas , Transdução de Sinais
3.
Nucleic Acids Res ; 46(D1): D649-D655, 2018 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-29145629

RESUMO

The Reactome Knowledgebase (https://reactome.org) provides molecular details of signal transduction, transport, DNA replication, metabolism, and other cellular processes as an ordered network of molecular transformations-an extended version of a classic metabolic map, in a single consistent data model. Reactome functions both as an archive of biological processes and as a tool for discovering unexpected functional relationships in data such as gene expression profiles or somatic mutation catalogues from tumor cells. To support the continued brisk growth in the size and complexity of Reactome, we have implemented a graph database, improved performance of data analysis tools, and designed new data structures and strategies to boost diagram viewer performance. To make our website more accessible to human users, we have improved pathway display and navigation by implementing interactive Enhanced High Level Diagrams (EHLDs) with an associated icon library, and subpathway highlighting and zooming, in a simplified and reorganized web site with adaptive design. To encourage re-use of our content, we have enabled export of pathway diagrams as 'PowerPoint' files.


Assuntos
Bases de Conhecimento , Redes e Vias Metabólicas , Gráficos por Computador , Bases de Dados de Compostos Químicos , Bases de Dados de Proteínas , Humanos , Internet , Anotação de Sequência Molecular , Transdução de Sinais , Interface Usuário-Computador
4.
Bioinformatics ; 33(21): 3461-3467, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29077811

RESUMO

Motivation: Reactome is a free, open-source, open-data, curated and peer-reviewed knowledge base of biomolecular pathways. Pathways are arranged in a hierarchical structure that largely corresponds to the GO biological process hierarchy, allowing the user to navigate from high level concepts like immune system to detailed pathway diagrams showing biomolecular events like membrane transport or phosphorylation. Here, we present new developments in the Reactome visualization system that facilitate navigation through the pathway hierarchy and enable efficient reuse of Reactome visualizations for users' own research presentations and publications. Results: For the higher levels of the hierarchy, Reactome now provides scalable, interactive textbook-style diagrams in SVG format, which are also freely downloadable and editable. Repeated diagram elements like 'mitochondrion' or 'receptor' are available as a library of graphic elements. Detailed lower-level diagrams are now downloadable in editable PPTX format as sets of interconnected objects. Availability and implementation: http://reactome.org. Contact: fabregat@ebi.ac.uk or hhe@ebi.ac.uk.


Assuntos
Fenômenos Biológicos , Bases de Conhecimento , Interface Usuário-Computador , Gráficos por Computador , Ontologia Genética , Internet , Bibliotecas , Transdução de Sinais
5.
Artigo em Inglês | MEDLINE | ID: mdl-27589961

RESUMO

Fully automated text mining (TM) systems promote efficient literature searching, retrieval, and review but are not sufficient to produce ready-to-consume curated documents. These systems are not meant to replace biocurators, but instead to assist them in one or more literature curation steps. To do so, the user interface is an important aspect that needs to be considered for tool adoption. The BioCreative Interactive task (IAT) is a track designed for exploring user-system interactions, promoting development of useful TM tools, and providing a communication channel between the biocuration and the TM communities. In BioCreative V, the IAT track followed a format similar to previous interactive tracks, where the utility and usability of TM tools, as well as the generation of use cases, have been the focal points. The proposed curation tasks are user-centric and formally evaluated by biocurators. In BioCreative V IAT, seven TM systems and 43 biocurators participated. Two levels of user participation were offered to broaden curator involvement and obtain more feedback on usability aspects. The full level participation involved training on the system, curation of a set of documents with and without TM assistance, tracking of time-on-task, and completion of a user survey. The partial level participation was designed to focus on usability aspects of the interface and not the performance per se In this case, biocurators navigated the system by performing pre-designed tasks and then were asked whether they were able to achieve the task and the level of difficulty in completing the task. In this manuscript, we describe the development of the interactive task, from planning to execution and discuss major findings for the systems tested.Database URL: http://www.biocreative.org.


Assuntos
Curadoria de Dados/métodos , Mineração de Dados/métodos , Processamento Eletrônico de Dados/métodos
6.
Nucleic Acids Res ; 44(D1): D481-7, 2016 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-26656494

RESUMO

The Reactome Knowledgebase (www.reactome.org) provides molecular details of signal transduction, transport, DNA replication, metabolism and other cellular processes as an ordered network of molecular transformations-an extended version of a classic metabolic map, in a single consistent data model. Reactome functions both as an archive of biological processes and as a tool for discovering unexpected functional relationships in data such as gene expression pattern surveys or somatic mutation catalogues from tumour cells. Over the last two years we redeveloped major components of the Reactome web interface to improve usability, responsiveness and data visualization. A new pathway diagram viewer provides a faster, clearer interface and smooth zooming from the entire reaction network to the details of individual reactions. Tool performance for analysis of user datasets has been substantially improved, now generating detailed results for genome-wide expression datasets within seconds. The analysis module can now be accessed through a RESTFul interface, facilitating its inclusion in third party applications. A new overview module allows the visualization of analysis results on a genome-wide Reactome pathway hierarchy using a single screen page. The search interface now provides auto-completion as well as a faceted search to narrow result lists efficiently.


Assuntos
Bases de Dados de Compostos Químicos , Redes e Vias Metabólicas , Expressão Gênica , Humanos , Bases de Conhecimento , Proteínas/metabolismo , Transdução de Sinais , Software
7.
Nucleic Acids Res ; 42(Database issue): D472-7, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24243840

RESUMO

Reactome (http://www.reactome.org) is a manually curated open-source open-data resource of human pathways and reactions. The current version 46 describes 7088 human proteins (34% of the predicted human proteome), participating in 6744 reactions based on data extracted from 15 107 research publications with PubMed links. The Reactome Web site and analysis tool set have been completely redesigned to increase speed, flexibility and user friendliness. The data model has been extended to support annotation of disease processes due to infectious agents and to mutation.


Assuntos
Bases de Dados de Proteínas , Proteínas/metabolismo , Doença , Humanos , Internet , Bases de Conhecimento , Redes e Vias Metabólicas
8.
Cancers (Basel) ; 4(4): 1180-211, 2012 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-24213504

RESUMO

Reactome describes biological pathways as chemical reactions that closely mirror the actual physical interactions that occur in the cell. Recent extensions of our data model accommodate the annotation of cancer and other disease processes. First, we have extended our class of protein modifications to accommodate annotation of changes in amino acid sequence and the formation of fusion proteins to describe the proteins involved in disease processes. Second, we have added a disease attribute to reaction, pathway, and physical entity classes that uses disease ontology terms. To support the graphical representation of "cancer" pathways, we have adapted our Pathway Browser to display disease variants and events in a way that allows comparison with the wild type pathway, and shows connections between perturbations in cancer and other biological pathways. The curation of pathways associated with cancer, coupled with our efforts to create other disease-specific pathways, will interoperate with our existing pathway and network analysis tools. Using the Epidermal Growth Factor Receptor (EGFR) signaling pathway as an example, we show how Reactome annotates and presents the altered biological behavior of EGFR variants due to their altered kinase and ligand-binding properties, and the mode of action and specificity of anti-cancer therapeutics.

9.
Nucleic Acids Res ; 35(14): 4869-81, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17626045

RESUMO

The binding of transcription factor (TF) IIIA to the internal control region of the 5 S RNA gene is the first step in the assembly of a DNA-TFIIIA-TFIIIC- TFIIIB transcription complex, which promotes accurate transcription by RNA polymerase III. With the use of mutations that are predicted to disrupt the folding of a zinc finger, we have examined the roles of zinc fingers 1 through 7 of yeast TFIIIA in the establishment of a functional transcription complex both in vitro and in vivo. Our data indicate that, in addition to their role in DNA binding, the first and seventh zinc fingers contribute other essential roles in the assembly of an active transcription complex. Alanine-scanning mutagenesis identified residues within zinc finger 1 that are not required for DNA binding but are required for incorporation of TFIIIC into the TFIIIA-DNA complex. Although disruption of zinc finger 2 or 3 had a deleterious effect on the activity of TFIIIA both in vitro and in vivo, we found that increasing the level of their in vivo expression allowed these mutant proteins to support cell viability. Disruption of zinc fingers 4, 5 or 6 had minimal effect on the DNA binding and TF activities of TFIIIA.


Assuntos
RNA Ribossômico 5S/genética , Proteínas de Saccharomyces cerevisiae/química , Fator de Transcrição TFIIIA/química , Dedos de Zinco , Alanina/genética , DNA Ribossômico/metabolismo , Ensaio de Desvio de Mobilidade Eletroforética , Mutagênese Sítio-Dirigida , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Fator de Transcrição TFIIIA/genética , Fator de Transcrição TFIIIA/metabolismo , Transcrição Genética
10.
Mol Cell Biol ; 25(15): 6772-88, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16024810

RESUMO

The divergently transcribed DIT1 and DIT2 genes of Saccharomyces cerevisiae, which belong to the mid-late class of sporulation-specific genes, are subject to Ssn6-Tup1-mediated repression in mitotic cells. The Ssn6-Tup1 complex, which is required for repression of diverse sets of coordinately regulated genes, is known to be recruited to target genes by promoter-specific DNA-binding proteins. In this study, we show that a 42-bp negative regulatory element (NRE) present in the DIT1-DIT2 intergenic region consists of two distinct subsites and that a multimer of each subsite supports efficient Ssn6-Tup1-dependent repression of a CYC1-lacZ reporter gene. By genetic screening procedures, we identified DFG16, YGR122w, VPS36, and the DNA-binding proteins Rim101 and Nrg1 as potential mediators of NRE-directed repression. We show that Nrg1 and Rim101 bind simultaneously to adjacent target sites within the NRE in vitro and act as corepressors in vivo. We have found that the ability of Rim101 to be proteolytically processed to its active form and mediate NRE-directed repression not only depends on the previously characterized RIM signaling pathway but also requires Dfg16, Ygr122w, and components of the ESCRT trafficking pathway. Interestingly, Rim101 was processed in bro1 and doa4 strains but was unable to mediate efficient repression.


Assuntos
Proteínas de Ligação a DNA/fisiologia , Regulação Fúngica da Expressão Gênica/fisiologia , Genes Fúngicos/fisiologia , Genes Reguladores/fisiologia , Hidroximetil e Formil Transferases/genética , Proteínas Repressoras/fisiologia , Proteínas de Saccharomyces cerevisiae/fisiologia , Saccharomyces cerevisiae/genética , Complexos Ubiquitina-Proteína Ligase/fisiologia , Sequência de Bases , Proteínas F-Box , Hidroximetil e Formil Transferases/biossíntese , Hidroximetil e Formil Transferases/fisiologia , Dados de Sequência Molecular , Transporte Proteico/genética , Transporte Proteico/fisiologia , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/biossíntese , Proteínas de Saccharomyces cerevisiae/genética , Esporos Fúngicos/genética , Esporos Fúngicos/fisiologia
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