RESUMO
RegulonDB is a database that contains the most comprehensive corpus of knowledge of the regulation of transcription initiation of Escherichia coli K-12, including data from both classical molecular biology and high-throughput methodologies. Here, we describe biological advances since our last NAR paper of 2019. We explain the changes to satisfy FAIR requirements. We also present a full reconstruction of the RegulonDB computational infrastructure, which has significantly improved data storage, retrieval and accessibility and thus supports a more intuitive and user-friendly experience. The integration of graphical tools provides clear visual representations of genetic regulation data, facilitating data interpretation and knowledge integration. RegulonDB version 12.0 can be accessed at https://regulondb.ccg.unam.mx.
Assuntos
Bases de Dados Genéticas , Escherichia coli K12 , Regulação Bacteriana da Expressão Gênica , Biologia Computacional/métodos , Escherichia coli K12/genética , Internet , Transcrição GênicaRESUMO
RegulonDB (http://regulondb.ccg.unam.mx) is one of the most useful and important resources on bacterial gene regulation,as it integrates the scattered scientific knowledge of the best-characterized organism, Escherichia coli K-12, in a database that organizes large amounts of data. Its electronic format enables researchers to compare their results with the legacy of previous knowledge and supports bioinformatics tools and model building. Here, we summarize our progress with RegulonDB since our last Nucleic Acids Research publication describing RegulonDB, in 2013. In addition to maintaining curation up-to-date, we report a collection of 232 interactions with small RNAs affecting 192 genes, and the complete repertoire of 189 Elementary Genetic Sensory-Response units (GENSOR units), integrating the signal, regulatory interactions, and metabolic pathways they govern. These additions represent major progress to a higher level of understanding of regulated processes. We have updated the computationally predicted transcription factors, which total 304 (184 with experimental evidence and 120 from computational predictions); we updated our position-weight matrices and have included tools for clustering them in evolutionary families. We describe our semiautomatic strategy to accelerate curation, including datasets from high-throughput experiments, a novel coexpression distance to search for 'neighborhood' genes to known operons and regulons, and computational developments.
Assuntos
Bases de Dados Genéticas , Escherichia coli K12/genética , Regulação Bacteriana da Expressão Gênica , Regulon , Análise por Conglomerados , Escherichia coli K12/metabolismo , Redes Reguladoras de Genes , Óperon , Matrizes de Pontuação de Posição Específica , Pequeno RNA não Traduzido/metabolismo , Fatores de Transcrição/classificaçãoRESUMO
RegulonDB provides curated information on the transcriptional regulatory network of Escherichia coli and contains both experimental data and computationally predicted objects. To account for the heterogeneity of these data, we introduced in version 6.0, a two-tier rating system for the strength of evidence, classifying evidence as either 'weak' or 'strong' (Gama-Castro,S., Jimenez-Jacinto,V., Peralta-Gil,M. et al. RegulonDB (Version 6.0): gene regulation model of Escherichia Coli K-12 beyond transcription, active (experimental) annotated promoters and textpresso navigation. Nucleic Acids Res., 2008;36:D120-D124.). We now add to our classification scheme the classification of high-throughput evidence, including chromatin immunoprecipitation (ChIP) and RNA-seq technologies. To integrate these data into RegulonDB, we present two strategies for the evaluation of confidence, statistical validation and independent cross-validation. Statistical validation involves verification of ChIP data for transcription factor-binding sites, using tools for motif discovery and quality assessment of the discovered matrices. Independent cross-validation combines independent evidence with the intention to mutually exclude false positives. Both statistical validation and cross-validation allow to upgrade subsets of data that are supported by weak evidence to a higher confidence level. Likewise, cross-validation of strong confidence data extends our two-tier rating system to a three-tier system by introducing a third confidence score 'confirmed'. Database URL: http://regulondb.ccg.unam.mx/
Assuntos
Biologia Computacional/métodos , Bases de Dados Genéticas , Escherichia coli/genética , Regulon/genética , Estatística como Assunto , Vias Biossintéticas/genética , Imunoprecipitação da Cromatina , Regulação Bacteriana da Expressão Gênica , Redes Reguladoras de Genes , Matrizes de Pontuação de Posição Específica , Reprodutibilidade dos Testes , Sítio de Iniciação de TranscriçãoRESUMO
The stationary-phase response mediated by the RpoS sigma factor (σ(S), σ³8) has been widely studied as a general mechanism of activation of highly diverse genes that maintain cell viability. In bacteria, genes for diverse functions have been associated with this response, showing that bacteria use a large number of functions to contend with adverse conditions in their environment. However, little is known about how the genes have been functionally recruited in diverse organisms. In this work, we address the analysis of genes regulated by σ(S), based on a comparative genomic-scale analysis considering four versatile bacterial species that represent different lifestyles and taxonomic groups, Escherichia coli K-12, Geobacter sulfurreducens, Borrelia burgdorferi and Bacillus subtilis, as well as the extent of conservation in bacterial genomes, as a means of assessing the evolution of this sigmulon across all organisms completely sequenced. The analysis presented here shows that genes associated with the σ(S) response have been recruited from diverse regulons to achieve a global response. In addition, and based on the distribution of orthologues, we show a group of genes that is highly conserved among all organisms, mainly associated with glycerol metabolism, as well as diverse functional genes recruited in a lineage-specific manner.
Assuntos
Bactérias/genética , Proteínas de Bactérias/genética , Evolução Molecular , Variação Genética , Genoma Bacteriano , Fator sigma/genética , Bactérias/classificação , Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Fator sigma/metabolismoAssuntos
Bactérias/genética , Biologia Computacional/métodos , Regulação Bacteriana da Expressão Gênica , Bacillus subtilis/genética , Biologia Computacional/tendências , DNA Bacteriano/genética , Eletrônica , Escherichia coli K12/genética , Genoma Bacteriano , Publicações Periódicas como Assunto , Pseudomonas aeruginosa/genética , EditoraçãoRESUMO
RegulonDB (http://regulondb.ccg.unam.mx/) is the primary reference database offering curated knowledge of the transcriptional regulatory network of Escherichia coli K12, currently the best-known electronically encoded database of the genetic regulatory network of any free-living organism. This paper summarizes the improvements, new biology and new features available in version 6.0. Curation of original literature is, from now on, up to date for every new release. All the objects are supported by their corresponding evidences, now classified as strong or weak. Transcription factors are classified by origin of their effectors and by gene ontology class. We have now computational predictions for sigma(54) and five different promoter types of the sigma(70) family, as well as their corresponding -10 and -35 boxes. In addition to those curated from the literature, we added about 300 experimentally mapped promoters coming from our own high-throughput mapping efforts. RegulonDB v.6.0 now expands beyond transcription initiation, including RNA regulatory elements, specifically riboswitches, attenuators and small RNAs, with their known associated targets. The data can be accessed through overviews of correlations about gene regulation. RegulonDB associated original literature, together with more than 4000 curation notes, can now be searched with the Textpresso text mining engine.
Assuntos
Bases de Dados Genéticas , Escherichia coli K12/genética , Regulação Bacteriana da Expressão Gênica , Redes Reguladoras de Genes , Biologia Computacional , Internet , Modelos Genéticos , Regiões Promotoras Genéticas , Sequências Reguladoras de Ácido Ribonucleico , Regulon , Fator sigma/metabolismo , Software , Fatores de Transcrição/metabolismo , Sítio de Iniciação de Transcrição , Transcrição GênicaRESUMO
RegulonDB is the internationally recognized reference database of Escherichia coli K-12 offering curated knowledge of the regulatory network and operon organization. It is currently the largest electronically-encoded database of the regulatory network of any free-living organism. We present here the recently launched RegulonDB version 5.0 radically different in content, interface design and capabilities. Continuous curation of original scientific literature provides the evidence behind every single object and feature. This knowledge is complemented with comprehensive computational predictions across the complete genome. Literature-based and predicted data are clearly distinguished in the database. Starting with this version, RegulonDB public releases are synchronized with those of EcoCyc since our curation supports both databases. The complex biology of regulation is simplified in a navigation scheme based on three major streams: genes, operons and regulons. Regulatory knowledge is directly available in every navigation step. Displays combine graphic and textual information and are organized allowing different levels of detail and biological context. This knowledge is the backbone of an integrated system for the graphic display of the network, graphic and tabular microarray comparisons with curated and predicted objects, as well as predictions across bacterial genomes, and predicted networks of functionally related gene products. Access RegulonDB at http://regulondb.ccg.unam.mx.
Assuntos
Bases de Dados Genéticas , Escherichia coli K12/genética , Regulação Bacteriana da Expressão Gênica , Óperon , Regulon , Escherichia coli K12/crescimento & desenvolvimento , Genoma Bacteriano , Internet , Software , Transcrição Gênica , Interface Usuário-ComputadorRESUMO
RegulonDB is the primary database of the major international maintained curation of original literature with experimental knowledge about the elements and interactions of the network of transcriptional regulation in Escherichia coli K-12. This includes mechanistic information about operon organization and their decomposition into transcription units (TUs), promoters and their sigma type, binding sites of specific transcriptional regulators (TRs), their organization into 'regulatory phrases', active and inactive conformations of TRs, as well as terminators and ribosome binding sites. The database is complemented with clearly marked computational predictions of TUs, promoters and binding sites of TRs. The current version has been expanded to include information beyond specific mechanisms aimed at gathering different growth conditions and the associated induced and/or repressed genes. RegulonDB is now linked with Swiss-Prot, with microarray databases, and with a suite of programs to analyze and visualize microarray experiments. We provide a summary of the biological knowledge contained in RegulonDB and describe the major changes in the design of the database. RegulonDB can be accessed on the web at the URL: http://www.cifn.unam.mx/Computational_Biology/regulondb/.