Causal Relationships¶

These relationship types denote a causal relationship, or the absence of a causal relationship between a subject and an object term.

Regulates¶

For terms A and B, A regulates B or A reg B indicate that A is reported to have an effect on B, but information is missing about whether A increases B or A decreases B. This relationship provides more information than association, association, because the upstream entity (source term) and downstream entity (target term) can be assigned.

This relationship is equivalent to RO:0002211.

There isn't currently a differentiation between direct regulation and indirect regulation, so right now this should be considered as indirect.

Increases¶

For terms A and B, A increases B or A -> B indicate that increases in A have been observed to cause increases in B.

Depending on the terms A and B, this relationship can be used to describe a phosphorylation event, the increase in the amount of a protein, the activation of a protein, the transportation of a protein, or several other things.

Directly Increases¶

For terms A and B, A directlyIncreases B or A => B indicates that increases in A have been observed to cause increases in B and that the mechanism of the causal relationship is based on physical interaction of entities related to A and B. This is a Direct Relationships, direct version of the increases relationship.

Decreases¶

For terms A and B, A decreases B or A -| B indicate that increases in A have been observed to cause decreases in B.

Depending on the terms A and B, this relationship can be used to describe a dephosphorylation event, the decrease in the amount of a protein, the deactivation of a protein, the inhibition of the transportation of a protein, or several other things.

Directly Decreases¶

For terms A and B, A directlyDecreases B or A =| B indicates that increases in A have been observed to cause decreases in B and that the mechanism of the causal relationship is based on physical interaction of entities related to A and B. This is a Direct Relationship, direct version of the decreases relationship.

For example, the inhibition of the Patched 1 receptor signaling activity by Hedgehog is represented as direct, because Hedgehog and Patched 1 physically interact:

# long form
p(fplx:Hedgehog) directlyDecreases act(p(hgnc:9585 ! PTCH1))

# short form
p(fplx:Hedgehog) =| act(p(hgnc:9585 ! PTCH1))

Example - Transcription Factors¶

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:3821 ! FOXO3), ma(tscript)) =| r(hgnc:31586 ! MIR21)

Example - Self-referential relationships¶

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:4617 ! GSK3B, pmod(Ph, Ser, 9)) =| act(p(hgnc:4617 ! GSK3B), ma(kin))

Rate Limiting Step¶

For process, activity, or transformation term A and process term P, A rateLimitingStepOf P indicates both:

A partOf bp(B)
A -> bp(B)

For example, the catalytic activity of HMG CoA reductase is a rate-limiting step for cholesterol biosynthesis:

act(p(hgnc:5006 ! HMGCR), ma(go:0003824 ! "catalytic activity")) rateLimitingStepOf bp(go:0006695 ! "cholesterol biosynthetic process")

Causes No Change¶

For terms A and B, A causesNoChange B or A cnc B indicate that B was observed not to change in response to changes in A.

Statements using this relationship correspond to cases where explicit measurement of B demonstrates lack of significant change, not for cases where the state of B is unknown.