Reactome MF verdict vocabulary

Back to Reactome-GO Alignment

Bottom line: every Reactome:R-* row should be classified at the same
granularity as the Reactome object that supports it. Reaction-like events can
support molecular functions on the protein that executes the chemistry or
transport; pathway containers can support only pathway/BP context; complex
events need the active member separated from scaffold, assembly, and regulatory
members. These verdicts give the inventory a compact way to count the repeated
cases before each affected gene review receives its final ACCEPT, MODIFY,
MARK_AS_OVER_ANNOTATED, REMOVE, or UNDECIDED action.

Verdicts

Verdict	Use when	Typical curation action
`reaction_mf_exact`	The stable ID is a catalyzed reaction or transport event, the gene product is the executor, and the GO MF matches the event chemistry or transported substrate class at the right specificity.	`ACCEPT`
`reaction_mf_refine`	The event is mechanistically sound evidence for the gene product, but the exported or local GO term is too broad, too narrow, or missing a substrate qualifier implied by the reaction.	`MODIFY`
`reaction_context_only`	The Reactome event is good evidence for localization or non-core pathway context on the executor, but it is not the row that should carry the molecular-function assertion.	`ACCEPT` or `KEEP_AS_NON_CORE` for CC/BP rows; keep out of MF counts
`complex_active_member`	A protein complex executes the reaction and this gene product is the catalytic, transport, receptor, or adaptor subunit that directly supplies the MF.	`ACCEPT`, often with explicit complex context
`complex_contributes_to`	The member is required for a complex MF but does not itself contain the active site or transport pore.	`MODIFY` to a `contributes_to` activity when available
`complex_over_export`	Reactome or GOA flattened a complex-level MF onto a scaffold, accessory, assembly, or regulatory subunit that does not perform the activity.	`MARK_AS_OVER_ANNOTATED` or `REMOVE`
`wrong_executor`	The Reactome event or GOA row names a real reaction, but the MF belongs to the redox partner, transfer partner, catalytic partner, or carrier rather than to this gene product.	`REMOVE`
`regulator_not_executor`	The gene product regulates or accelerates a reaction but is not itself the GTPase, kinase, transporter, or other executor named by the MF.	`REMOVE`
`wrong_transport_mechanism`	The gene product moves cargo by vesicle selection, sorting, or another non-channel/non-carrier mechanism, while the GO term asserts movement across a lipid bilayer.	`REMOVE`
`wrong_go_branch`	The Reactome reaction is assigned to the wrong molecular-function branch, such as an oxygen-acceptor methyltransferase exported as an S-methyltransferase.	`REMOVE` or `MARK_AS_OVER_ANNOTATED`
`obsolete_go_term`	The row uses an obsolete GO molecular-function term even if the underlying reaction evidence is otherwise interpretable.	`REMOVE` or `MODIFY`
`activity_contradicted`	The stable ID comes from a family or legacy event that is contradicted by direct evidence for this paralog or by explicit NOT annotations on the same gene.	`REMOVE`
`contested_direct_activity`	The Reactome event records a historical direct-activity model that has been weakened by newer mechanism work and should not be treated as settled.	`MARK_AS_OVER_ANNOTATED` or `UNDECIDED`
`nonphysiological_side_activity`	The reaction has weak in-vitro support but is not a physiological or representative function of the gene product.	`MARK_AS_OVER_ANNOTATED` or `KEEP_AS_NON_CORE`
`pathway_container_bp`	The stable ID names a Reactome pathway and the gene product performs one of the pathway's molecular steps, making the BP assertion valid but less precise than the direct MF.	usually `KEEP_AS_NON_CORE`
`pathway_container_overreach`	A pathway stable ID is being used as if it were a reaction, or the pathway/BP assertion only reflects downstream necessity, a substrate role, or generic membership.	`MARK_AS_OVER_ANNOTATED`, `MODIFY`, or `REMOVE`
`input_product_only`	The entity linked to the event is only consumed, produced, or carried by the reaction and does not catalyze, transport, recruit, or structurally enable the step.	`REMOVE` for executor-like MF/BP rows
`black_box_gap`	Reactome records that the reaction occurs but has no assigned catalyst or transporter, and AIGR has a plausible candidate from gene reviews.	feed into `REACTOME_GAP_FILLING`, not an automatic GO row
`boundary_mismatch`	A transport or membrane event uses the right substrate class but the GO term, compartment, or direction crosses a different boundary than Reactome.	`MODIFY` or `UNDECIDED`
`insufficient_event_detail`	The cached Reactome Markdown is a pathway summary or free-text statement that does not expose enough participants, compartments, or catalyst roles to decide.	`UNDECIDED` until the event graph can be checked

Pathway Comparator Verdicts

ingest_reactome_pathways.py emits a narrower set of event-to-module verdicts
for local pathway comparisons:

Verdict	Use when
`reaction_id_exact`	The local activity cites the same Reactome stable ID, Reactome exposes an exact accessioned executor, and the GO MF ID matches the event activity.
`same_reaction_mf_unconfirmed`	The local activity cites the same Reactome stable ID and the exact executor matches, but the Reactome MF and local GO MF IDs differ. This can be a benign parent/child specificity difference or a wrong GO branch that needs manual review.
`same_reaction_executor_unconfirmed`	The local activity cites the same Reactome stable ID and overlaps a Reactome `Complex`, `DefinedSet`, or `CandidateSet`, but the exact active accession is not established by the comparator.
`same_reaction_missing_executor`	The local activity cites the same Reactome stable ID, but no imported catalyst member overlaps the local executor.
`same_executor_different_reaction`	A Reactome-only or module-only event shares an exact accessioned executor with an event on the other side under a different Reactome stable ID.
`reactome_only_event`	The imported Reactome subtree has a reaction-like event that is not cited by the local module.
`black_box_event`	The imported Reactome subtree has a `BlackBoxEvent` without explicit catalyst members.
`unmatched_family_event`	The imported Reactome subtree has an uncited set/candidate-set catalyst with no exact local executor match.
`module_only_event`	A local module activity cites a Reactome stable ID absent from the imported pathway slice.

Counting Rules

Count the Reactome stable ID itself, not only the GO term. One GO term can be
clean for a reaction stable ID and over-broad for a pathway-container stable
ID.
Classify pathway stable IDs before comparing MFs. A pathway container that
mentions the reaction family is still not one individual MF event.
Assign complex_active_member, complex_contributes_to, or
complex_over_export only after checking which entity supplies the active
site, pore, receptor binding, adaptor recruitment, or structural cofactor
activity.
Use input_product_only for substrates and products that are necessary but
passive. Those relationships belong on the executor through has input, not
as a process annotation on the substrate.
Use black_box_gap for missing Reactome participants. It is a Reactome
curation candidate first; a new GO annotation still needs ordinary gene-level
evidence.
Keep manual splits for REMOVE and MARK_AS_OVER_ANNOTATED rows in
mf_manual_verdicts.yaml. A review action alone
does not distinguish a wrong GO branch from a regulator/executor swap or a
paralog-specific contradiction.

Pilot Calibration

The first purine nucleotide interconversion pilot establishes two positive
controls and one exclusion:

Stable ID	Verdict	Reason
`R-HSA-73792`	`reaction_mf_exact`	The stable ID is a direct soluble reaction and its chemistry matches the local GMPS MF.
`R-HSA-111524`, `R-HSA-73794`, `R-HSA-76590`	`same_reaction_executor_unconfirmed`	The ADSS, IMPDH, and AMP deaminase chemistries match, but Reactome represents each enzyme family as a `DefinedSet`; these family events are not exact executor assertions for any one paralog.
Same four reaction IDs on human gene-review cytosol rows	`reaction_context_only`	The rows in completed reviews are accepted CC rows, not MF rows, even though the same event also matches a local MF.
`R-HSA-73817`	`pathway_container_bp`	The stable ID names a purine biosynthesis pathway; it can support BP context but is excluded from one-to-one reaction/MF matching.

MF Failure-Mode Calibration

The first manual pass over MARK_AS_OVER_ANNOTATED and REMOVE MF rows split
37 previously blank rows:

Failure mode	Rows	Typical example
`reaction_mf_refine` / `broad_parent_or_duplicate`	19	Correct Reactome reaction, but exported to a broad parent such as `GO:0008168` methyltransferase activity
`activity_contradicted`	5	A Reactome family event assigned to a paralog whose direct biochemistry contradicts the family activity
`contested_direct_activity`	3	Historical MAGT1/TUSC3 magnesium-transporter events versus newer OST-B oxidoreductase evidence
`regulator_not_executor`	3	RGS or GAP regulators exported as the substrate GTPase
`wrong_executor`	2	A redox or cofactor-transfer partner receiving the enzyme or carrier MF
`wrong_go_branch`	2	Correct chemical event mapped to the wrong GO branch
`nonphysiological_side_activity`	1	A weak in-vitro steroid reaction exported as an SRD5A3 MF
`obsolete_go_term`	1	An old ATPase-coupled anion transporter term on CFTR
`wrong_transport_mechanism`	1	AP-4 cargo selection exported as transmembrane protein transport