BRENDA, the ELIXIR core data resource in 2021: new developments and updates.

The BRENDA enzyme database (https://www.brenda-enzymes.org), established in 1987, has evolved into the main collection of functional enzyme and metabolism data. In 2018, BRENDA was selected as an ELIXIR Core Data Resource. BRENDA provides reliable data, continuous curation and updates of classified enzymes, and the integration of newly discovered enzymes. The main part contains >5 million data for ∼90 000 enzymes from ∼13 000 organisms, manually extracted from ∼157 000 primary literature references, combined with information of text and data mining, data integration, and prediction algorithms. Supplements comprise disease-related data, protein sequences, 3D structures, genome annotations, ligand information, taxonomic, bibliographic, and kinetic data. BRENDA offers an easy access to enzyme information from quick to advanced searches, text- and structured-based queries for enzyme-ligand interactions, word maps, and visualization of enzyme data. The BRENDA Pathway Maps are completely revised and updated for an enhanced interactive and intuitive usability. The new design of the Enzyme Summary Page provides an improved access to each individual enzyme. A new protein structure 3D viewer was integrated. The prediction of the intracellular localization of eukaryotic enzymes has been implemented. The new EnzymeDetector combines BRENDA enzyme annotations with protein and genome databases for the detection of eukaryotic and prokaryotic enzymes.

BRENDA in 2019: a European ELIXIR core data resource.

The BRENDA enzyme database (www.brenda-enzymes.org), recently appointed ELIXIR Core Data Resource, is the main enzyme and enzyme-ligand information system. The core database provides a comprehensive overview on enzymes. A collection of 4.3 million data for ∼84 000 enzymes manually evaluated and extracted from ∼140 000 primary literature references is combined with information obtained by text and data mining, data integration and prediction algorithms. Supplements comprise disease-related data, protein sequences, 3D structures, predicted enzyme locations and genome annotations. Major developments are a revised ligand summary page and the structure search now including a similarity and isomer search. BKMS-react, an integrated database containing known enzyme-catalyzed reactions, is supplemented with further reactions and improved access to pathway connections. In addition to existing enzyme word maps with graphical information of enzyme specific terms, plant word maps have been developed. They show a graphical overview of terms, e.g. enzyme or plant pathogen information, connected to specific plants. An organism summary page showing all relevant information, e.g. taxonomy and synonyms linked to enzyme data, was implemented. Based on a decision by the IUBMB enzyme task force the enzyme class EC 7 has been established for 'translocases', enzymes that catalyze a transport of ions or metabolites across cellular membranes.

BRENDA in 2017: new perspectives and new tools in BRENDA.

The BRENDA enzyme database (www.brenda-enzymes.org) has developed into the main enzyme and enzyme-ligand information system in its 30 years of existence. The information is manually extracted from primary literature and extended by text mining procedures, integration of external data and prediction algorithms. Approximately 3 million data from 83 000 enzymes and 137 000 literature references constitute the manually annotated core. Text mining procedures extend these data with information on occurrence, enzyme-disease relationships and kinetic data. Prediction algorithms contribute locations and genome annotations. External data and links complete the data with sequences and 3D structures. A total of 206 000 enzyme ligands provide functional and structural data. BRENDA offers a complex query tool engine allowing the users an efficient access to the data via different search methods and explorers. The new design of the BRENDA entry page and the enzyme summary pages improves the user access and the performance. New interactive and intuitive BRENDA pathway maps give an overview on biochemical processes and facilitate the visualization of enzyme, ligand and organism information in the biochemical context. SCOPe and CATH, databases for protein structure classification, are included. New online and video tutorials provide online training for the users. BRENDA is freely available for academic users.

BRENDA in 2015: exciting developments in its 25th year of existence.

The BRENDA enzyme information system (http://www.brenda-enzymes.org/) has developed into an elaborate system of enzyme and enzyme-ligand information obtained from different sources, combined with flexible query systems and evaluation tools. The information is obtained by manual extraction from primary literature, text and data mining, data integration, and prediction algorithms. Approximately 300 million data include enzyme function and molecular data from more than 30,000 organisms. The manually derived core contains 3 million data from 77,000 enzymes annotated from 135,000 literature references. Each entry is connected to the literature reference and the source organism. They are complemented by information on occurrence, enzyme/disease relationships from text mining, sequences and 3D structures from other databases, and predicted enzyme location and genome annotation. Functional and structural data of more than 190,000 enzyme ligands are stored in BRENDA. New features improving the functionality and analysis tools were implemented. The human anatomy atlas CAVEman is linked to the BRENDA Tissue Ontology terms providing a connection between anatomical and functional enzyme data. Word Maps for enzymes obtained from PubMed abstracts highlight application and scientific relevance of enzymes. The EnzymeDetector genome annotation tool and the reaction database BKM-react including reactions from BRENDA, KEGG and MetaCyc were improved. The website was redesigned providing new query options.

BRENDA in 2013: integrated reactions, kinetic data, enzyme function data, improved disease classification: new options and contents in BRENDA.

The BRENDA (BRaunschweig ENzyme DAtabase) enzyme portal (http://www.brenda-enzymes.org) is the main information system of functional biochemical and molecular enzyme data and provides access to seven interconnected databases. BRENDA contains 2.7 million manually annotated data on enzyme occurrence, function, kinetics and molecular properties. Each entry is connected to a reference and the source organism. Enzyme ligands are stored with their structures and can be accessed via their names, synonyms or via a structure search. FRENDA (Full Reference ENzyme DAta) and AMENDA (Automatic Mining of ENzyme DAta) are based on text mining methods and represent a complete survey of PubMed abstracts with information on enzymes in different organisms, tissues or organelles. The supplemental database DRENDA provides more than 910 000 new EC number-disease relations in more than 510 000 references from automatic search and a classification of enzyme-disease-related information. KENDA (Kinetic ENzyme DAta), a new amendment extracts and displays kinetic values from PubMed abstracts. The integration of the EnzymeDetector offers an automatic comparison, evaluation and prediction of enzyme function annotations for prokaryotic genomes. The biochemical reaction database BKM-react contains non-redundant enzyme-catalysed and spontaneous reactions and was developed to facilitate and accelerate the construction of biochemical models.

Development of a classification scheme for disease-related enzyme information.

BACKGROUND: BRENDA (BRaunschweig ENzyme DAtabase, http://www.brenda-enzymes.org) is a major resource for enzyme related information. First and foremost, it provides data which are manually curated from the primary literature. DRENDA (Disease RElated ENzyme information DAtabase) complements BRENDA with a focus on the automatic search and categorization of enzyme and disease related information from title and abstracts of primary publications. In a two-step procedure DRENDA makes use of text mining and machine learning methods. RESULTS: Currently enzyme and disease related references are biannually updated as part of the standard BRENDA update. 910,897 relations of EC-numbers and diseases were extracted from titles or abstracts and are included in the second release in 2010. The enzyme and disease entity recognition has been successfully enhanced by a further relation classification via machine learning. The classification step has been evaluated by a 5-fold cross validation and achieves an F1 score between 0.802 ± 0.032 and 0.738 ± 0.033 depending on the categories and pre-processing procedures. In the eventual DRENDA content every category reaches a classification specificity of at least 96.7% and a precision that ranges from 86-98% in the highest confidence level, and 64-83% for the smallest confidence level associated with higher recall. CONCLUSIONS: The DRENDA processing chain analyses PubMed, locates references with disease-related information on enzymes and categorises their focus according to the categories causal interaction, therapeutic application, diagnostic usage and ongoing research. The categorisation gives an impression on the focus of the located references. Thus, the relation categorisation can facilitate orientation within the rapidly growing number of references with impact on diseases and enzymes. The DRENDA information is available as additional information in BRENDA.

BRENDA, the enzyme information system in 2011.

The BRENDA (BRaunschweig ENzyme Database, http://www.brenda-enzymes.org) enzyme information system is the main collection of enzyme functional and property data for the scientific community. The majority of the data are manually extracted from the primary literature. The content covers information on function, structure, occurrence, preparation and application of enzymes as well as properties of mutants and engineered variants. The number of manually annotated references increased by 30% to more than 100,000, the number of ligand structures by 45% to almost 100,000. New query, analysis and data management tools were implemented to improve data processing, data presentation, data input and data access. BRENDA now provides new viewing options such as the display of the statistics of functional parameters and the 3D view of protein sequence and structure features. Furthermore a ligand summary shows comprehensive information on the BRENDA ligands. The enzymes are linked to their respective pathways and can be viewed in pathway maps. The disease text mining part is strongly enhanced. It is possible to submit new, not yet classified enzymes to BRENDA, which then are reviewed and classified by the International Union of Biochemistry and Molecular Biology. A new SBML output format of BRENDA kinetic data allows the construction of organism-specific metabolic models.

The BRENDA Tissue Ontology (BTO): the first all-integrating ontology of all organisms for enzyme sources.

BTO, the BRENDA Tissue Ontology (http://www.BTO.brenda-enzymes.org) represents a comprehensive structured encyclopedia of tissue terms. The project started in 2003 to create a connection between the enzyme data collection of the BRENDA enzyme database and a structured network of source tissues and cell types. Currently, BTO contains more than 4600 different anatomical structures, tissues, cell types and cell lines, classified under generic categories corresponding to the rules and formats of the Gene Ontology Consortium and organized as a directed acyclic graph (DAG). Most of the terms are endowed with comments on their derivation or definitions. The content of the ontology is constantly curated with ∼1000 new terms each year. Four different types of relationships between the terms are implemented. A versatile web interface with several search and navigation functionalities allows convenient online access to the BTO and to the enzymes isolated from the tissues. Important areas of applications of the BTO terms are the detection of enzymes in tissues and the provision of a solid basis for text-mining approaches in this field. It is widely used by lab scientists, curators of genomic and biochemical databases and bioinformaticians. The BTO is freely available at http://www.obofoundry.org.

BRENDA, AMENDA and FRENDA the enzyme information system: new content and tools in 2009.

The BRENDA (BRaunschweig ENzyme DAtabase) (http://www.brenda-enzymes.org) represents the largest freely available information system containing a huge amount of biochemical and molecular information on all classified enzymes as well as software tools for querying the database and calculating molecular properties. The database covers information on classification and nomenclature, reaction and specificity, functional parameters, occurrence, enzyme structure and stability, mutants and enzyme engineering, preparation and isolation, the application of enzymes, and ligand-related data. The data in BRENDA are manually curated from more than 79,000 primary literature references. Each entry is clearly linked to a literature reference, the origin organism and, where available, to the protein sequence of the enzyme protein. A new search option provides the access to protein-specific data. FRENDA (Full Reference ENzyme DAta) and AMENDA (Automatic Mining of ENzyme DAta) are additional databases created by continuously improved text-mining procedures. These databases ought to provide a complete survey on enzyme data of the literature collection of PubMed. The web service via a SOAP (Simple Object Access Protocol) interface for access to the BRENDA data has been further enhanced.

BRENDA, AMENDA and FRENDA: the enzyme information system in 2007.

The BRENDA (BRaunschweig ENzyme DAtabase) enzyme information system (http://www.brenda.uni-koeln.de) is the largest publicly available enzyme information system worldwide. The major parts of its contents are manually extracted from primary literature. It is not restricted to specific groups of enzymes, but includes information on all identified enzymes irrespective of the enzyme's source. The range of data encompasses functional, structural, sequence, localisation, disease-related, isolation, stability information on enzyme and ligand-related data. Each single entry is linked to the enzyme source and to a literature reference. Recently the data repository was complemented by text-mining data in AMENDA (Automatic Mining of ENzyme DAta) and FRENDA (Full Reference ENzyme DAta). A genome browser, membrane protein prediction and full-text search capacities were added. The newly implemented web service provides instant access to the data for programmers via a SOAP (Simple Object Access Protocol) interface. The BRENDA data can be downloaded in the form of a text file from the beginning of 2007.

BRENDA, the enzyme database: updates and major new developments.

BRENDA (BRaunschweig ENzyme DAtabase) represents a comprehensive collection of enzyme and metabolic information, based on primary literature. The database contains data from at least 83,000 different enzymes from 9800 different organisms, classified in approximately 4200 EC numbers. BRENDA includes biochemical and molecular information on classification and nomenclature, reaction and specificity, functional parameters, occurrence, enzyme structure, application, engineering, stability, disease, isolation and preparation, links and literature references. The data are extracted and evaluated from approximately 46,000 references, which are linked to PubMed as long as the reference is cited in PubMed. In the past year BRENDA has undergone major changes including a large increase in updating speed with >50% of all data updated in 2002 or in the first half of 2003, the development of a new EC-tree browser, a taxonomy-tree browser, a chemical substructure search engine for ligand structure, the development of controlled vocabulary, an ontology for some information fields and a thesaurus for ligand names. The database is accessible free of charge to the academic community at http://www.brenda. uni-koeln.de.

BRENDA: a resource for enzyme data and metabolic information.

BRENDA (BRaunschweig ENzyme DAtabase), founded in 1987 by Dietmar Schomburg, is a comprehensive protein function database, containing enzymatic and metabolic information extracted from the primary literature. Presently, the database holds data on more than 40 000 enzymes and 4460 different organisms, and includes information about enzyme-ligand relationships with numerous chemical compounds. The collection of molecular and biochemical information in BRENDA provides a fundamental resource for research in biotechnology, pharmacology, medicinal diagnostics, enzyme mechanics, and metabolism. BRENDA is accessible free of charge to the academic community at http://www.brenda.uni-koeln.de/; commercial users need a license available from http://www.science-factory.com/

BRENDA, enzyme data and metabolic information.

BRENDA is a comprehensive relational database on functional and molecular information of enzymes, based on primary literature. The database contains information extracted and evaluated from approximately 46 000 references, holding data of at least 40 000 different enzymes from more than 6900 different organisms, classified in approximately 3900 EC numbers. BRENDA is an important tool for biochemical and medical research covering information on properties of all classified enzymes, including data on the occurrence, catalyzed reaction, kinetics, substrates/products, inhibitors, cofactors, activators, structure and stability. All data are connected to literature references which in turn are linked to PubMed. The data and information provide a fundamental tool for research of enzyme mechanisms, metabolic pathways, the evolution of metabolism and, furthermore, for medicinal diagnostics and pharmaceutical research. The database is a resource for data of enzymes, classified according to the EC system of the IUBMB Enzyme Nomenclature Committee, and the entries are cross-referenced to other databases, i.e. organism classification, protein sequence, protein structure and literature references. BRENDA provides an academic web access at http://www.brenda.uni-koeln.de.