The BTOGremse, M., Chang, A., Schomburg, I., Grote, A., Scheer, M., Ebeling, C., Schomburg, D. (2011): �
The BRENDA Tissue Ontology (BTO): the first all-integrating ontology of all organisms for enzyme sources
��, ''Nucleic Acids Res.'', 39 (Database issue): D507–D513
BRENDA Tissue Ontology
represents a comprehensive structured

encyclopedia An encyclopedia (American English) or encyclopædia (British English) is a reference work or compendium providing summaries of knowledge either general or special to a particular field or discipline. Encyclopedias are divided into articles ...

. It provides terms, classifications, and definitions of tissues,

organs In biology, an organ is a collection of tissues joined in a structural unit to serve a common function. In the hierarchy of life, an organ lies between tissue and an organ system. Tissues are formed from same type cells to act together in a fu ...

, anatomical structures, plant parts,

cell culture Cell culture or tissue culture is the process by which cells are grown under controlled conditions, generally outside of their natural environment. The term "tissue culture" was coined by American pathologist Montrose Thomas Burrows. This te ...

cell type A cell type is a classification used to identify cells that share morphological or phenotypical features. A multicellular organism may contain cells of a number of widely differing and specialized cell types, such as muscle cells and skin cells, ...

s, and cell lines of organisms from all taxonomic groups (

animal Animals are multicellular, eukaryotic organisms in the Kingdom (biology), biological kingdom Animalia. With few exceptions, animals Heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, are Motilit ...

plant Plants are predominantly photosynthetic eukaryotes of the kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all current definitions of Plantae exclud ...

s, fungis,

protozoon Protozoa (singular: protozoan or protozoon; alternative plural: protozoans) are a group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic tissues and debris. Histor ...

) as enzyme sources. The information is connected to the functional data in the

BRENDA Brenda is a feminine given name in the English language. Origin The overall accepted origin for the female name Brenda is the Old Nordic male name ''Brandr'' meaning both ''torch'' and ''sword'': evidently the male name Brandr took root in areas ...

("BRaunschweig ENzyme DAtabase“)Chang, A., Jeske, L., Ulbrich, S., Hofmann, J., Koblitz, J., Schomburg, I., Neumann-Schaal, M., Jahn, D., Schomburg, D. (2021): �
BRENDA, the ELIXIR core data resource in 2021: new developments and updates
��, ''Nucleic Acids Res.'', 49 (Database issue): D498–D508

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

information system. BTO is one of the first tissue-specific ontologies in

life sciences This list of life sciences comprises the branches of science that involve the scientific study of life – such as microorganisms, plants, and animals including human beings. This science is one of the two major branches of natural science, the ...

, not restricted to a specific organism or a specific organism group providing a user-friendly access to the wide range of tissue and cell-type information. Databases, such as ''Ontology Lookup Service'' or ses, such as '' MIRIAM Registry'' or of the EBI-EMBL, the ''TissueDistributionDB'', including the ''Tissue Synonym Library'' of the German Cancer Research Center (DKFZ) in Heidelberg or the ''Bioportal'' platform of the National Center for Biomedical Ontology in Stanford, USA rely on BTO and implement the encyclopedia as an essential repository of information into their respective platform. BTO enables users from

medical research Medical research (or biomedical research), also known as experimental medicine, encompasses a wide array of research, extending from "basic research" (also called ''bench science'' or ''bench research''), – involving fundamental scientif ...

and pharmaceutical sciences to search for the occurrence and histological detection of disease-related enzymes in tissues, which play an important role in

diagnosis Diagnosis is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in many different disciplines, with variations in the use of logic, analytics, and experience, to determine " cause and effect". In systems engin ...

, therapies, and drug development. In

biochemistry Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology and ...

and

biotechnology Biotechnology is the integration of natural sciences and engineering sciences in order to achieve the application of organisms, cells, parts thereof and molecular analogues for products and services. The term ''biotechnology'' was first used b ...

the organism-specific tissue terms linked to enzyme functional data are an important resource for the understanding of the metabolism and regulation in life sciences. Ontologies represent classification systems that provide controlled and structured vocabularies.Schomburg, I., Chang, A., Schomburg, D. (2014): �
Standardization in enzymology—Data integration in the world's enzyme information system BRENDA
��, ''Perspectives in Science'', 1: 15–23 They are important tools to illustrate and to link evolutionary correlations. Development of BTO started in 2003, aimed to connect the biochemical and molecular biological enzyme data of BRENDA with a hierarchical and standardized collection of tissue-specific terms. The functional enzyme data and information in BRENDA have been manually annotated and structured by experts from biochemistry, biology, and chemistry. By October 2022, the BTO contained over 6,527 terms, linked to 6,065 synonyms and 5,474 definitions. The terms are classified under generic categories, rules, and formats of the Gene Ontology Consortium (GO,Roncaglia, P., Martone, M.E., Hill, D.P., Berardini, T.Z., Foulger, R.E., Imam, F.T., Drabkin, H., Mungall, C.J., Lomax, J. (2013): �
The Gene Ontology (GO) Cellular Component Ontology: integration with SAO (Subcellular Anatomy Ontology) and other recent developments
��, ''J. Biomed. Semantics'', 4: 20), organized as a directed acyclic graph (DAG) created using the

open-source Open source is source code that is made freely available for possible modification and redistribution. Products include permission to use the source code, design documents, or content of the product. The open-source model is a decentralized sof ...

OBO-Edit.Smith, B., Ashburner, M., Rosse, C., Bard, J., Bug, W., Ceusters, W., Goldberg, L.J., Eilbeck, K., Ireland, A., Mungall, C.J.; OBI Consortium, Leontis, N., Rocca-Serra, P., Ruttenberg, A., Sansone, S.A., Scheuermann, R.H., Shah, N., Whetzel,P.L,, Lewis, S. (2010): �
The OBO Foundry: coordinated evolution of ontologies to support biomedical data integration
��, ''Nat. Biotechnol.'', 25: 1251–1255 All terms from each level are directly connected the enzyme data in BRENDA. BTO is a suitable tool to distinguish between different enzymes which are expressed in a tissue-specific manner.

Content and Features

BTO draws upon the comprehensive enzyme specific data of the BRENDA enzyme information system. Presently (October 2019) 112,200 enzyme-organism-tissue specific data from more than 11,000 proteins are stored in BRENDA. These entries were manually annotated from more than 150,000 different literature references. All terms in BTO are evaluated and classified according to the OBO-format, and are connected by specific relationships. Each term is a distinct entry within the ontology and is automatically assigned to a unique BTO-identifier (BTO-ID). The BTO-IDs serve as stable accession numbers in order to create cross-references to further external biochemical databases. Further tissue und cell-type specific terms from external databases (i.e. UniProt) are integrated into BTO. The terms are classified in 4 main categories (subgraphs): * animal * plant * fungus * other sources Further levels are defined below the main categories (=nodes), classifying the “parent”, “child”, and “grandchild” all connected via specific relationships (=edges) * is_a (e.g. skeletal muscle fibre is_a muscle fibre) * part_of (e.g. muscle fibre part_of muscle) * develops/derives_from (e.g.myoma cell develops/derives_from muscle fibre) * related_to (description of more general relationships between terms which are not covered by the other ones) Most of the terms are clearly associated with specific organisms, organs, tissues, or cell types. However, there are several identical designations for tissues both in plants and animals, e.g. “epidermis”. To distinguish between those tissue terms and to classify them correctly into BTO for plant tissues the prefix “plant” is placed before the term, e.g. “plant epidermis”. More than 80% of the tissue terms have definitions that describe the meaning and context. These definitions are obtained from i.e. medical dictionaries and cell line databases (

Webster's Dictionary ''Webster's Dictionary'' is any of the English language dictionaries edited in the early 19th century by American lexicographer Noah Webster (1758–1843), as well as numerous related or unrelated dictionaries that have adopted the Webster's n ...

DSMZ The Leibniz Institute DSMZ - German Collection of Microorganisms and Cell Cultures GmbH (German: ''Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH''), located in Braunschweig, is a research infrastructure in th ...

Availability

The entries in BTO are updated bi-annually as part of the major update of BRENDA. It is available via the BRENDA website in the category �
Ontology Explorer
��. The enzyme source terms can be searched via the BTO query form. As a result, the user receives a list of EC numbers which are directly connected to the enzyme information of BRENDA. It is also possible to search via the BRENDA “Source Tissue” search form (“Classic View”). The result page displays all enzymes which are isolated or detected in the searched tissue term, directly linked to BTO. BTO and BRENDA are freely accessible for academic users. It can be freely downloaded via the �
Ontology Explorer
�� of the BRENDA website or in the OBO format from �

��.

Literature References

Links

BTO (BRENDA Tissue Ontology)

BRENDA Ontology Explorer

BRENDA-website

ExplorEnz – Enzyme Nomenclature

Gene Ontology Consortium

EBI-EMBL

Bioportal des National Center for Biomedical Ontology, Stanford, USA
Biological databases Ontology (information science) Cell culture Developmental biology Biochemistry Enzymes