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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.
Autophagy ; 17(6): 1543-1554, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32486891

RESUMO

The 21st century has revealed much about the fundamental cellular process of autophagy. Autophagy controls the catabolism and recycling of various cellular components both as a constitutive process and as a response to stress and foreign material invasion. There is considerable knowledge of the molecular mechanisms of autophagy, and this is still growing as new modalities emerge. There is a need to investigate autophagy mechanisms reliably, comprehensively and conveniently. Reactome is a freely available knowledgebase that consists of manually curated molecular events (reactions) organized into cellular pathways (https://reactome.org/). Pathways/reactions in Reactome are hierarchically structured, graphically presented and extensively annotated. Data analysis tools, such as pathway enrichment, expression data overlay and species comparison, are also available. For customized analysis, information can also be programmatically queried. Here, we discuss the curation and annotation of the molecular mechanisms of autophagy in Reactome. We also demonstrate the value that Reactome adds to research by reanalyzing a previously published work on genome-wide CRISPR screening of autophagy components.Abbreviations: CMA: chaperone-mediated autophagy; GO: Gene Ontology; MA: macroautophagy; MI: microautophagy; MTOR: mechanistic target of rapamycin kinase; SQSTM1: sequestosome 1.

5.
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
6.
Database (Oxford) ; 20192019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31802127

RESUMO

Reactome is a manually curated, open-source, open-data knowledge base of biomolecular pathways. Reactome has always provided clear credit attribution for authors, curators and reviewers through fine-grained annotation of all three roles at the reaction and pathway level. These data are visible in the web interface and provided through the various data download formats. To enhance visibility and credit attribution for the work of authors, curators and reviewers, and to provide additional opportunities for Reactome community engagement, we have implemented key changes to Reactome: contributor names are now fully searchable in the web interface, and contributors can 'claim' their contributions to their ORCID profile with a few clicks. In addition, we are reaching out to domain experts to request their help in reviewing and editing Reactome pathways through a new 'Contribution' section, highlighting pathways which are awaiting community review. Database URL: https://reactome.org.


Assuntos
Curadoria de Dados , Transdução de Sinais , Interface Usuário-Computador
7.
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
8.
RNA ; 22(5): 667-76, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26917558

RESUMO

MicroRNA regulation of developmental and cellular processes is a relatively new field of study, and the available research data have not been organized to enable its inclusion in pathway and network analysis tools. The association of gene products with terms from the Gene Ontology is an effective method to analyze functional data, but until recently there has been no substantial effort dedicated to applying Gene Ontology terms to microRNAs. Consequently, when performing functional analysis of microRNA data sets, researchers have had to rely instead on the functional annotations associated with the genes encoding microRNA targets. In consultation with experts in the field of microRNA research, we have created comprehensive recommendations for the Gene Ontology curation of microRNAs. This curation manual will enable provision of a high-quality, reliable set of functional annotations for the advancement of microRNA research. Here we describe the key aspects of the work, including development of the Gene Ontology to represent this data, standards for describing the data, and guidelines to support curators making these annotations. The full microRNA curation guidelines are available on the GO Consortium wiki (http://wiki.geneontology.org/index.php/MicroRNA_GO_annotation_manual).


Assuntos
Guias como Assunto , MicroRNAs/genética , Animais , Inativação Gênica , Humanos , Camundongos
9.
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
10.
J Pharm Technol ; 31(3): 104-114, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34860923

RESUMO

Background: The marriage of cutting-edge technology to the practice of pharmacy for the purpose of promoting patient safety and enhancing pharmacy workflow is an exciting and continuous evolution. Objective: To assess whether the incorporation of portable tablet technology into a mock patient counseling exercise enhances or detracts from the overall counseling experience. Methods: Second professional year Doctor of Pharmacy students enrolled in a pharmacy practice laboratory were randomly assigned to either a portable tablet or a desktop computer group. During patient counseling, students using the portable tablet were required to incorporate the device into the counseling session in addition to written notations; the desktop computer group was allowed to utilize only written notations. Surveys were developed and distributed to students and instructors following each counseling session. Survey data and numerical grades earned for each counseling session were collected and analyzed. Results: One hundred seventy-eight students participated in the study. Survey data revealed students in the portable tablet group were more satisfied with their patient counseling sessions, as well as more confident during their interactions. Instructor grading revealed similar earned numerical grades for both study groups. Instructors noted little or no difference between the groups with regard to counseling effectiveness; however, students in the portable tablet group appeared more engaged with their mock patients. Conclusion: Incorporation of a portable tablet during a patient education session did not detract from, and may have enhanced, the experience. However, the essential components of the pharmacist-patient interaction remain vital, and technology should not become the focus of the interaction.

11.
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
12.
Database (Oxford) ; 2013: bas056, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23327936

RESUMO

In many databases, biocuration primarily involves literature curation, which usually involves retrieving relevant articles, extracting information that will translate into annotations and identifying new incoming literature. As the volume of biological literature increases, the use of text mining to assist in biocuration becomes increasingly relevant. A number of groups have developed tools for text mining from a computer science/linguistics perspective, and there are many initiatives to curate some aspect of biology from the literature. Some biocuration efforts already make use of a text mining tool, but there have not been many broad-based systematic efforts to study which aspects of a text mining tool contribute to its usefulness for a curation task. Here, we report on an effort to bring together text mining tool developers and database biocurators to test the utility and usability of tools. Six text mining systems presenting diverse biocuration tasks participated in a formal evaluation, and appropriate biocurators were recruited for testing. The performance results from this evaluation indicate that some of the systems were able to improve efficiency of curation by speeding up the curation task significantly (∼1.7- to 2.5-fold) over manual curation. In addition, some of the systems were able to improve annotation accuracy when compared with the performance on the manually curated set. In terms of inter-annotator agreement, the factors that contributed to significant differences for some of the systems included the expertise of the biocurator on the given curation task, the inherent difficulty of the curation and attention to annotation guidelines. After the task, annotators were asked to complete a survey to help identify strengths and weaknesses of the various systems. The analysis of this survey highlights how important task completion is to the biocurators' overall experience of a system, regardless of the system's high score on design, learnability and usability. In addition, strategies to refine the annotation guidelines and systems documentation, to adapt the tools to the needs and query types the end user might have and to evaluate performance in terms of efficiency, user interface, result export and traditional evaluation metrics have been analyzed during this task. This analysis will help to plan for a more intense study in BioCreative IV.


Assuntos
Mineração de Dados , Educação , Bases de Dados como Assunto , Documentação , Humanos , Software , Fatores de Tempo
13.
Biochem Mol Biol Educ ; 40(3): 181-90, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22615226

RESUMO

Genome scale experiments routinely produce large data sets that require computational analysis, yet there are few student-based labs that illustrate the design and execution of these experiments. In order for students to understand and participate in the genomic world, teaching labs must be available where students generate and analyze large data sets. We present a microarray-based gene expression analysis experiment that is tailored for undergraduate students. The methods in this article describe an expression analysis experiment that can also be applied to CGH and SNP experiments. Factors such as technical difficulty, duration, cost, and availability of materials and equipments are considered in the lab design. The microarray teaching lab is performed in two sessions. The first is an introductory wet bench exercise that allows students to master the basic technical skills. The second builds on the concepts and skills with students acquiring and analyzing the microarray data. This lab exercise familiarizes students with large-scale data experiments and introduces them to the initial analysis steps.


Assuntos
Disciplinas das Ciências Biológicas/educação , Expressão Gênica , Genômica/educação , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Aprendizagem Baseada em Problemas/métodos , Disciplinas das Ciências Biológicas/métodos , Currículo , Genômica/métodos , Humanos , Processamento de Imagem Assistida por Computador , Grupo Associado , Estudantes , Fatores de Tempo
14.
J Cell Mol Med ; 16(4): 649-56, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21880114

RESUMO

Mast cell function and dysregulation is important in the development and progression of allergic and autoimmune disease. Identifying novel proteins involved in mast cell function and disease progression is the first step in the design of new therapeutic strategies. Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are a family of proteins demonstrated to mediate the transport and fusion of secretory vesicles to the membrane in mast cells, leading to the subsequent release of the vesicle cargo through an exocytotic mechanism. The functional role[s] of specific SNARE family member complexes in mast cell degranulation has not been fully elucidated. Here, we review recent and historical data on the expression, formation and localization of various SNARE proteins and their complexes in murine and human mast cells. We summarize the functional data identifying the key SNARE family members that appear to participate in mast cell degranulation. Furthermore, we discuss the utilization of RNA interference (RNAi) methods to validate SNARE function and the use of siRNA as a therapeutic approach to the treatment of inflammatory disease. These studies provide an overview of the specific SNARE proteins and complexes that serve as novel targets for the development of new therapies to treat allergic and autoimmune disease.


Assuntos
Degranulação Celular , Mastócitos/citologia , Animais , Humanos , Camundongos , Interferência de RNA , Proteínas SNARE
15.
Nucleic Acids Res ; 39(Database issue): D691-7, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21067998

RESUMO

Reactome (http://www.reactome.org) is a collaboration among groups at the Ontario Institute for Cancer Research, Cold Spring Harbor Laboratory, New York University School of Medicine and The European Bioinformatics Institute, to develop an open source curated bioinformatics database of human pathways and reactions. Recently, we developed a new web site with improved tools for pathway browsing and data analysis. The Pathway Browser is an Systems Biology Graphical Notation (SBGN)-based visualization system that supports zooming, scrolling and event highlighting. It exploits PSIQUIC web services to overlay our curated pathways with molecular interaction data from the Reactome Functional Interaction Network and external interaction databases such as IntAct, BioGRID, ChEMBL, iRefIndex, MINT and STRING. Our Pathway and Expression Analysis tools enable ID mapping, pathway assignment and overrepresentation analysis of user-supplied data sets. To support pathway annotation and analysis in other species, we continue to make orthology-based inferences of pathways in non-human species, applying Ensembl Compara to identify orthologs of curated human proteins in each of 20 other species. The resulting inferred pathway sets can be browsed and analyzed with our Species Comparison tool. Collaborations are also underway to create manually curated data sets on the Reactome framework for chicken, Drosophila and rice.


Assuntos
Bases de Dados Factuais , Modelos Biológicos , Fenômenos Biológicos , Gráficos por Computador , Bases de Dados Genéticas , Bases de Dados de Proteínas , Regulação da Expressão Gênica , Humanos , Internet , Redes e Vias Metabólicas , Transdução de Sinais
16.
Mamm Genome ; 22(1-2): 130-8, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21052677

RESUMO

The innate immune responses mediated by Toll-like receptors (TLR) provide an evolutionarily well-conserved first line of defense against microbial pathogens. In the Reactome Knowledgebase we previously integrated annotations of human TLR molecular functions with those of over 4000 other human proteins involved in processes such as adaptive immunity, DNA replication, signaling, and intermediary metabolism, and have linked these annotations to external resources, including PubMed, UniProt, EntrezGene, Ensembl, and the Gene Ontology to generate a resource suitable for data mining, pathway analysis, and other systems biology approaches. We have now used a combination of manual expert curation and computer-based orthology analysis to generate a set of annotations for TLR molecular function in the chicken (Gallus gallus). Mammalian and avian lineages diverged approximately 300 million years ago, and the avian TLR repertoire consists of both orthologs and distinct new genes. The work described here centers on the molecular biology of TLR3, the host receptor that mediates responses to viral and other doubled-stranded polynucleotides, as a paradigm for our approach to integrated manual and computationally based annotation and data analysis. It tests the quality of computationally generated annotations projected from human onto other species and supports a systems biology approach to analysis of virus-activated signaling pathways and identification of clinically useful antiviral measures.


Assuntos
Galinhas/genética , Biologia Computacional , Evolução Molecular , Mamíferos/genética , Transdução de Sinais , Receptores Toll-Like/genética , Animais , Galinhas/classificação , Humanos , Mamíferos/classificação , Mamíferos/metabolismo , Dados de Sequência Molecular , Receptores Toll-Like/metabolismo
17.
Nucleic Acids Res ; 37(Database issue): D619-22, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18981052

RESUMO

Reactome (http://www.reactome.org) is an expert-authored, peer-reviewed knowledgebase of human reactions and pathways that functions as a data mining resource and electronic textbook. Its current release includes 2975 human proteins, 2907 reactions and 4455 literature citations. A new entity-level pathway viewer and improved search and data mining tools facilitate searching and visualizing pathway data and the analysis of user-supplied high-throughput data sets. Reactome has increased its utility to the model organism communities with improved orthology prediction methods allowing pathway inference for 22 species and through collaborations to create manually curated Reactome pathway datasets for species including Arabidopsis, Oryza sativa (rice), Drosophila and Gallus gallus (chicken). Reactome's data content and software can all be freely used and redistributed under open source terms.


Assuntos
Bases de Dados de Proteínas , Fenômenos Fisiológicos , Proteínas/metabolismo , Animais , Humanos , Redes e Vias Metabólicas , Modelos Animais , Proteínas/genética , Proteínas/fisiologia , Transdução de Sinais , Software , Integração de Sistemas
18.
Genome Biol ; 8(3): R39, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17367534

RESUMO

Reactome http://www.reactome.org, an online curated resource for human pathway data, provides infrastructure for computation across the biologic reaction network. We use Reactome to infer equivalent reactions in multiple nonhuman species, and present data on the reliability of these inferred reactions for the distantly related eukaryote Saccharomyces cerevisiae. Finally, we describe the use of Reactome both as a learning resource and as a computational tool to aid in the interpretation of microarrays and similar large-scale datasets.


Assuntos
Biologia Computacional/métodos , Bases de Conhecimento , Redes e Vias Metabólicas , Biologia de Sistemas , Animais , Bases de Dados como Assunto , Humanos , Internet , Análise em Microsséries , Saccharomyces cerevisiae
19.
Expert Opin Drug Discov ; 1(5): 389-94, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23495941

RESUMO

Many proteomic technologies require a heavy investment in expertise and technology, which place these approaches beyond many labs and small companies. However, proteomic approaches are ideal for pilot experiments, identifying relevant biomarkers and protein pathways for development or analysis of therapeutic compounds. The two-hybrid proteomic systems are available and affordable to most researchers, requiring little more than standard microbiological equipment. The screens rapidly generate data, identifying protein interactions that can be used to construct small local protein networks. Using data from large-scale projects, these small local protein networks can be used to identify the larger cellular pathways that are being affected by therapeutic compounds in the screen. The foundation for the two-hybrid proteomic systems are commercially available, as are high quality cDNA libraries. The straightforwardness of the two-hybrid proteomic system allows smaller groups to focus their resources on critical cellular pathways and molecular targets by taking advantage of a trusted molecular assay and an ever growing set of postgenomic era databases.

20.
Curr Opin Mol Ther ; 5(3): 266-70, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12870436

RESUMO

Numerous proteomic methodologies exist, but most require a heavy investment in expertise and technology. This puts these approaches out of reach for many laboratories and small companies, rarely allowing proteomics to be used as a pilot approach for biomarker or target identification. Two proteomic approaches, 2D gel electrophoresis and the two-hybrid systems, are currently available to most researchers. The two-hybrid systems, though accommodating to large-scale experiments, were originally designed as practical screens, that by comparison to current proteomics tools were small-scale, affordable and technically feasible. The screens rapidly generated data, identifying protein interactions that were previously uncharacterized. The foundation for a two-hybrid proteomic investigation can be purchased as separate kits from a number of companies. The true power of the technique lies not in its affordability, but rather in its portability. The two-hybrid system puts proteomics back into laboratories where the output of the screens can be evaluated by researchers with experience in the particular fields of basic research, cancer biology, toxicology or drug development.


Assuntos
Proteômica/economia , Proteômica/métodos , Técnicas do Sistema de Duplo-Híbrido/economia , Biblioteca Gênica , Humanos , Proteínas/análise , Kit de Reagentes para Diagnóstico
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