Knowledge in BEL is expressed as BEL Statements. Generally, BEL Statements have the form of a subject – predicate – object triple, where the subject is a BEL Term, the predicate is one of the BEL relationship types (e.g., increases), and the object can be either a BEL Term or a BEL Statement. A BEL Statement may also be comprised of a subject term only.

BEL Terms are composed of BEL Functions applied to concepts referenced using Namespace identifiers. Each BEL Term represents either an abundance of a biological entity, e.g., human AKT1 protein, or a process such as apoptosis.

BEL Annotations are applied to BEL Statements to optionally express additional information about the statement itself such as the citation for the publication reporting the observation, or the context in which the observation was made (e.g., species, tissue, cell line).

1.1. Namespaces

BEL is specifically designed to adopt external vocabularies and ontologies, and represent life-science knowledge in the language and schema of the organization collecting or using the knowledge. Thus, BEL Terms are defined by reference to concepts in external vocabularies, which provide a set of well-known domain values, such as the official human gene symbols provided by HGNC (http://www.genenames.org/) . While we consider it good practice to define biological entities with respect to well-defined domains such as public ontologies, no specific vocabulary is essential to the use of BEL, and users are free to define and reference their own vocabularies as needed.

BEL uses Namespaces to unambiguously reference concepts. The user associates a Namespace prefix with an external vocabulary and uses the prefix to refer to elements of the vocabulary. For example, if we associate the Namespace prefix HGNC with the vocabulary of symbols managed by the HGNC committee, we can then compose BEL Terms by referencing the HGNC Namespace prefix and any concept from the HGNC namespace together with a relevant BEL Function, e.g., proteinAbundance(HGNC:AKT1) or rnaAbundance(HGNC:TNF).

1.1.1. Equivalencing between Namespaces

Values from different Namespaces may correspond to the same biological concept. For example, the name AKT1 in the HGNC Namespace refers to the same gene referenced with ID 207 in the EGID (Entrez Gene Identifier) Namespace. The BEL Framework assembles knowledge into a cohesive network, mapping equivalent BEL Terms, e.g., proteinAbundance(HGNC:AKT1) and proteinAbundance(EGID:207), to a single node in the network. This correspondence of Namespace values is handled in the BEL Framework separately from BEL knowledge representation.

1.2. Terms

Two general categories of biological entities are represented as BEL Terms: abundances and processes.

1.2.1. Abundances

Life science experiments often measure the abundance of a type of thing in a given sample or set of samples. BEL Abundance Terms represent classes of abundance, the abundances of specific types of things. Examples include the protein abundance of TP53, the RNA abundance of CCND1, the abundance of the protein AKT1 phosphorylated at serine 21, or the abundance of the complex of the proteins CCND1 and CDK4.

1.2.2. Processes

BEL Process Terms represent classes of complex phenomena taking place at the level of the cell or the organism, such as the biological process of cell cycle or a disease process such as Cardiomyopathy. In other cases, BEL Terms may represent classes of specific molecular activities, such as the kinase activity of the AKT1 protein, or a specific chemical reaction like conversion of superoxides to hydrogen peroxide and oxygen.

Measurable biological parameters such as Blood Pressure or Body Temperature are represented as process BEL Terms. These BEL Terms denote biological activities that, when measured, are reduced to an output parameter.

1.2.3. BEL Terms as Functional Expressions

BEL Terms are denoted by expressions composed of a BEL Function and a list of arguments. BEL v2.0 specifies a set of approximately 20 functions allowed in term expressions.

The combination of a BEL function and its arguments fully specifies a BEL Term. The BEL Term expression f(a) denotes a BEL Term defined by function f() applied to an argument a. Wherever the same function is applied to the same arguments, the resulting BEL Term references the same biological entity.

The semantics of a BEL Term are determined by the function used in the term expression. For example, the function proteinAbundance() is defined such that any term expression using proteinAbundance() represents a class of abundance of protein. Many BEL functions take only single values as arguments, providing a structured method of using ontologies and vocabularies in BEL. For example, values in the HUGO Gene Nomenclature Committee (HGNC) vocabulary of official human gene symbols can be used to designate gene, RNA, and protein abundances. The function proteinAbundance() could then be applied to an HGNC gene symbol, AKT1 for example, to indicate the class of protein abundances produced by the AKT1 gene, producing the BEL Term proteinAbundance(HGNC:AKT1).

1.3. Statements

A BEL Statement represents an experimental observation, generally reported in a scientific publication or unpublished experimental data. Generally, BEL Statements express a causal or correlative relationship between two biological entities. Because BEL Terms are functionally composed, a BEL Statement can consist of a single BEL Term; this simple statement indicates that the biological entity represented by the term has been observed.

1.3.1. Example BEL Statements

Subject Term Only
complex(p(HGNC:CCND1), p(HGNC:CDK4))

The abundance of a complex formed from protein abundances designated by CCND1 and CDK4 in the HGNC namespace. This is a subject term only statement, and indicates that the entity specified by the term has been observed.

Causal
p(HGNC:CCND1) => act(p(HGNC:CDK4))

The abundance of the protein designated by CCND1 in the HGNC namespace directly increases the activity of the abundance of the protein designated by CDK4 in the HGNC namespace.

Causal
p(HGNC:BCL2)-| bp(MESHPP:Apoptosis)

The abundance of the protein designated by BCL2 in the HGNC namespace decreases the biological process designated by apoptosis in the MESHPP (phenomena and processes) namespace.

Nested Statement – Object Term is Statement
p(HGNC:GATA1) => ( act(p(HGNC:ZBTB16)) => r(HGNC:MPL) )

The abundance of the protein designated by GATA1 in the HGNC namespace directly increases the process in which the activity of the protein abundance designated by ZBTB16 in the HGNC namespace directly increases the abundance of RNA designated by MPL in the HGNC namespace.

1.4. Annotations

Each BEL Statement can optionally be annotated to express knowledge about the statement itself. Some important uses of annotations are to specify information about the:

  • biological system in which the observation represented by the statement was made

  • experimental methods used to demonstrate the observation

  • knowledge source on which the statement is based, such as the citation and specific text supporting the statement

Examples of annotations that could be associated with a BEL Statement are the:

  • PubMed ID specifying the publication in which the observation was reported,

  • Species, tissue, and cellular location in which the observations were made, and

  • Dosage, exposure and recovery time associated with the observation.