Direct relationships include direct causal relationships and non-causal relationships that are considered direct because they are self-referential.
The direct casual relationships included in BEL v2.0 are directlyIncreases (=>) and directlyDecreases (=|).
Direct casual relationships are causal relationships where the mechanism of the causal relationship is based on the physical interaction of entities related to the BEL Statement subject and object terms.
If A or B is an abundance, then members of the abundance are part of the interaction. If A or B are <
Inhibition of the Patched 1 receptor signaling activity by Hedgehog is represented as direct, because Hedgehog and Patched 1 physically interact:
p(PFH:"Hedgehog Family") =| act(p(HGNC:PTCH1))
In the case of transcriptional activity, if the protein performing the transcriptional activity interacts with the gene that the RNA is transcribed from, the relationship is considered direct. For example, repression of the transcription of miR-21 by FOXO3 protein transcriptional activity is represented as direct because FOXO3 binds the miR-21 promoter:
act(p(HGNC:FOXO3),ma(tscript)) =| r(HGNC:MIR21)
If B is a BEL Statement, the relationship is considered direct if the subject abundance term for B physically interacts with the abundance term for A. For example, for the BEL Statement:
p(HGNC:CLSPN) => (act(p(HGNC:ATR), ma(kin)) => p(HGNC:CHEK1, pmod(Ph)))
CLSPN protein is considered to directly activate the phosphorylation of CHEK1 protein by the kinase activity of ATR, because the CLSPN and ATR proteins physically interact.
Self-referential causal relationships are generally represented as direct. For example, phosphorylation of GSK3B at serine 9 inhibiting the kinase activity of GSK3B can be represented as:
p(HGNC:GSK3B, pmod(Ph, S, 9)) =| act(p(HGNC:GSK3B), ma(kin))