IntAct curates 47 interactions against engineered MLL fusion proteins, and every accession-keyed query in this project is blind to all of them - while its PSICQUIC mirror stops at 2024
also called MLL fusion construct interactors in IntAct · PSICQUIC versus IntAct REST currency · EBI-2890930 MLL-AF9 fusion interactor
The interaction database this project measures its coverage against contains experiments done directly on laboratory-made MLL fusion proteins - the exact kind of evidence the project says it lacks. Those entries have no standard protein identifier, so every automated query here misses them completely.
The same thing, for a scientist
Two independent instrument defects, both found while adjudicating the cycle-54 interactome read queue, both verified against live endpoints on 2026-09-22. **First: IntAct holds four engineered KMT2A/MLL-fusion INTERACTORS carrying 47 interaction records between them** - `EBI-2890930` "MLL-AF9 fusion protein" with 32, `EBI-2620068` mll_enl with 8, `EBI-2620048` mll_aff4 with 6 and `EBI-2620075` mll_aff4-1 with 1 - and **all four have an empty `interactorXrefs` list and an `interactorPreferredIdentifier` equal to their own IntAct accession**, i.e. no UniProt, no Ensembl, no gene name [E1]. Every interactome analysis in this repository queries by UniProt accession and every one resolves a partner's gene symbol from a `(gene name)` alias token, so **all 47 records are structurally invisible**, and the one that does leak through - the MED19 row - was mis-attributed by `analyses/core-complex-interactome-gap/run.py` to both its KMT2A query and its AFF4 query because PSICQUIC free-text matched the construct's description [E1][E2]. This matters because the project's recurring finding is that its evidence is partner-imported, with **0 of 24 sampled load-bearing experiments resting on a dedicated human KMT2A::AFF1 experiment**: here are 47 curated records whose bait or prey IS a KMT2A fusion protein. **Second: IntAct's PSICQUIC mirror is stale by at least a year.** For AFF4 (Q9UHB7) PSICQUIC serves 179 rows over 23 distinct publications with a **maximum PMID of 39251607 (2024)** and **zero rows from PMID 40205054** - a Nature 2025 5,100-protein U2OS multimodal map that IntAct REST does serve [E3][E4]. The read queue's per-partner publication lists are therefore floors, and the brief's "two papers may be one platform" warning was right about what the queue can see and incomplete about what exists [E4].
Defect 1: the fusion-construct interactors, and what is in them
IntAct models an engineered chimera as its own interactor with a free-text description and no cross-references at all 1:
| IntAct interactor | interactorName | description in the record | interactionCount | interactorXrefs |
|---|---|---|---|---|
EBI-2890930 | mll_af9_human_protein | MLL-AF9 fusion protein | 32 | [] |
EBI-2620068 | mll_enl_human_protein | Fusion of human MLL (N-terminal region) with human ENL C-terminal residues 373-559 | 8 | [] |
EBI-2620048 | mll_aff4_fusion | Fusion of Human MLL (N -terminus) and Human AFF4 (518-1163) -C terminal region | 6 | [] |
EBI-2620075 | mll_aff4_fusion-1 | Fusion of human MLL (N-terminal region) and human AFF4 (C terminal region) | 1 | [] |
47 interaction records. The six on EBI-2620048, enumerated in full: MED19 once (PMID 21729782, HeLa, anti-tag co-IP), MED26 four times (same publication and system), and AFF1 once (PMID 20153263, HEK293T, anti-tag co-IP) 1. The AFF1 row's publication is the AF4/ENL/P-TEFb higher-order complex paper that this graph already treats as load-bearing 5.
Why every query here misses them. analyses/core-complex-interactome-gap/run.py and analyses/aff1-interactome-gap both query by UniProt accession and both resolve a partner's identity with a regex for uniprotkb:([A-Za-z0-9._-]+)\(gene name\) 2. A fusion-construct interactor's MITAB alias field is psi-mi:mll_aff4_fusion(display_short)|psi-mi:EBI-2620048(display_long) - no (gene name) token - so gene_of() returns None and the row is dropped from the union, from the read queue and from the coverage denominator alike 2.
And when one does leak through, it is mis-attributed. PSICQUIC's free-text search/query/<accession> is not an id: query, so query/Q03164 and query/Q9UHB7 BOTH return the EBI-4321349 MED19 row - the same single interaction, counted once under KMT2A and once under AFF4. The read queue's MED19 n_baits: 2 is that artefact, and neither bait is what MED19 was tested against 2.
This is rule 93's family with a new member. Rule 93 established that a processed-chain identifier is a different identifier from its parent, and that the taspase1 fragments' records are filed separately from Q03164. This is the further case: an interactor with NO identifier at all, which no accession-keyed query can reach by any spelling.
Defect 2: PSICQUIC is stale, and the coverage figure is computed on it
Measured on two accessions, both endpoints, 2026-09-22 34:
| endpoint | AFF4 (Q9UHB7) | PIP4K2A (P48426) |
|---|---|---|
PSICQUIC search/query/<acc> rows | 179 | 234 |
| PSICQUIC distinct PMIDs | 23 | 17 |
| PSICQUIC maximum PMID | 39251607 (2024) | 39251607 (2024) |
| PSICQUIC rows from PMID 40205054 | 0 | 0 |
IntAct REST findInteractions/<acc> indexed interactions | 179 (same order) | 320 |
| IntAct REST rows from PMID 40205054 | present | present |
PMID 40205054 is Schaffer LV et al., Nature 2025 - a joint biophysical-interaction and immunofluorescence map of over 5,100 proteins in U2OS osteosarcoma cells, resolving 275 molecular assemblies 4. It is a genuinely independent platform from BioPlex: different laboratory, different cell line, and an orthogonal imaging modality.
The consequence for this project's headline interactome number. analyses/core-complex-interactome-gap/results.json reported 217 union human partners of the six core baits, 89 with an entry (41.0%) and 119 absent entirely; re-running it after this tranche's five entries gives 94/217 (43.3%) with 112 absent and the read queue down from 20 rows to 15, the denominator unchanged. So it is "live" by date and by corpus - and it is still live against a mirror whose newest publication is from 2024. Both the numerator and the denominator are floors, the 2025 depositions are wholly absent, and nothing in the results file says so.
Which way the error runs. The denominator (217) is too small, so partners exist that the queue has never nominated. The per-partner publications lists are too short, so a row that looks like a single platform may have two: CAMKV, PIP4K2A and EPB41L1 each gained a publication between the PSICQUIC snapshot and the REST query 4. The dispatch brief's warning that "a row saying 2 paper(s) may rest on a single method" is correct about the queue's own contents and understates the evidence for three of the seven partners in this tranche.
This is not a reason to silently re-run. Per rule 93 item 4, switching endpoints changes every n unevenly between baits. The recommendation is that run.py be moved to IntAct REST and both numbers carried, with a banner, rather than the figure quietly corrected.
A third, smaller trap found doing this: IntAct accession search matches by substring
Querying findInteractions/EBI-2620048 returns 7 rows where IntAct's own interactionCount for that interactor is 6 1.
The extra row is S100B - NEDD8 from PMID 32814053, a neurodegenerative-disease interactome mapping study 6. Its interaction accession is EBI-26200486, which contains the queried string EBI-2620048 as a prefix. The same collision adds a SPATS1 - SARS1 row to a query on EBI-2620075 (via EBI-26200754).
The control that identifies it is cheap and general: in a spurious row, neither participant is the queried interactor. Any beat querying IntAct by accession rather than by UniProt id should apply it, because IntAct accessions grew by an order of magnitude as the database grew, so short early accessions are prefixes of long recent ones - and the number of collisions will increase over time, not decrease.
What to do about it, and the part that is a research opportunity rather than a bug report
Instrument fixes, in order of value:
- Enumerate the four fusion-construct interactors explicitly. They cannot be discovered by accession, so they have to be named.
EBI-2890930,EBI-2620068,EBI-2620048,EBI-2620075. Add them as extra "baits" toanalyses/core-complex-interactome-gap/run.pyand the 47 records become visible. - Make
gene_of()record an unresolvable partner instead of dropping it. A row whose alias field has no(gene name)token should increment a named counter and be listed, not vanish. This is the repository's own rule that a field which is absent must be recorded absent rather than searched for elsewhere - applied to a partner rather than to an accession. - Make every interactome filter isoform-tolerant. Strip a trailing
-Nbefore comparing accessions. Measured in this tranche: CAMKV's twelve rows split six-and-six betweenQ8NCB2andQ8NCB2-2, and an exact-match filter sees two publications instead of three. - Move to IntAct REST and carry both numbers. Do not silently correct 89/217.
And the research opportunity, which is the reason this entry exists. This project's most-quoted self-criticism is that its evidence is partner-imported - 0 of 24 sampled load-bearing experiments rest on a dedicated human KMT2A::AFF1 experiment, and the standing caveat on every IntAct partner is that an interactor of KMT2A is not an interactor of the fusion. Forty-seven curated interaction records exist in which a KMT2A fusion protein is itself a participant, thirty-two of them on MLL-AF9, and this graph has never read any of them. They are laboratory chimeras rather than endogenous t(4;11) products, so they are not a substitute for the index fusion - but they are a strictly better class of evidence than a wild-type KMT2A partner, and they are one query away.
| script | none (live endpoint comparison: IntAct REST versus IntAct PSICQUIC, plus reading analyses/core-complex-interactome-gap/run.py) |
|---|---|
| status | run |
| result summary | IntAct holds 47 interaction records against four engineered MLL-fusion constructs, none of which carries any cross-reference, so every accession-keyed query in this repository is blind to all of them; and IntAct's PSICQUIC mirror - the endpoint the 89/217 coverage figure is computed on - serves no publication newer than PMID 39251607 (2024), omitting a Nature 2025 5,100-protein U2OS map that adds a second independent platform to three of this tranche's seven partners. |
| absence class | measured-not-curated |
inputs
[ "IntAct REST ws/interactor/findInteractor and ws/interaction/findInteractions, retrieved 2026-09-22", "IntAct PSICQUIC search/query/<accession>?format=tab25&maxResults=4000, retrieved 2026-09-22", "analyses/core-complex-interactome-gap/run.py (read, and executed against both endpoints)", "NCBI E-utilities efetch for every publication identifier quoted" ]
defect 1 fusion construct interactors
{
"interactors": [
{
"intact_ac": "EBI-2890930",
"name": "mll_af9_human_protein",
"description": "MLL-AF9 fusion protein",
"interaction_count": 32,
"xrefs": "empty",
"preferred_identifier": "its own IntAct AC",
"enumerated_here": false
},
{
"intact_ac": "EBI-2620068",
"name": "mll_enl_human_protein",
"description": "Fusion of human MLL (N-terminal region) with human ENL C-terminal residues 373-559",
"interaction_count": 8,
"xrefs": "empty",
"preferred_identifier": "its own IntAct AC",
"enumerated_here": false
},
{
"intact_ac": "EBI-2620048",
"name": "mll_aff4_fusion",
"description": "Fusion of Human MLL (N -terminus) and Human AFF4 (518-1163) -C terminal region",
"interaction_count": 6,
"xrefs": "empty",
"preferred_identifier": "its own IntAct AC",
"enumerated_here": true,
"partners": [
"MED19 x1 (PMID 21729782, HeLa)",
"MED26 x4 (PMID 21729782, HeLa)",
"AFF1 x1 (PMID 20153263, HEK293T)"
]
},
{
"intact_ac": "EBI-2620075",
"name": "mll_aff4_fusion-1",
"description": "Fusion of human MLL (N-terminal region) and human AFF4 (C terminal region)",
"interaction_count": 1,
"xrefs": "empty",
"preferred_identifier": "its own IntAct AC",
"enumerated_here": true,
"partners": [
"AFF1 x1 (PMID 20153263, HEK293T)"
]
}
],
"total_interaction_records": 47,
"records_enumerated_in_this_entry": 7,
"search_stems_tried": [
"mll_af4",
"mll_aff1",
"mll_fusion",
"mll_enl",
"mll_af9"
],
"search_stems_returning_records": [
"mll_enl",
"mll_af9"
],
"set_is_a_floor": "Only five name stems were tried and two returned records, so four interactors is a lower bound and not an exhaustive enumeration.",
"why_invisible": "Both interactome gap analyses query by UniProt accession and resolve partner identity with the regex uniprotkb:([A-Za-z0-9._-]+)\\(gene name\\). A fusion construct's MITAB alias field is psi-mi:<name>(display_short)|psi-mi:<AC>(display_long) with NO (gene name) token, so gene_of() returns None and the row is dropped from the union, the read queue and the coverage denominator - silently and without a counter.",
"leakage_artifact": "PSICQUIC search/query/<accession> is free-text, not id-scoped, so query/Q03164 and query/Q9UHB7 both return the same MED19 interaction EBI-4321349. The read queue's MED19 n_baits of 2 is that double attribution, and neither KMT2A nor AFF4 is what MED19 was tested against.",
"why_it_matters": "This project's most-quoted self-criticism is that 0 of 24 sampled load-bearing experiments rest on a dedicated human KMT2A::AFF1 experiment, and its standing caveat is that an interactor of KMT2A is not an interactor of the fusion. Forty-seven curated records exist whose participant IS a KMT2A fusion protein, thirty-two of them on MLL-AF9, and this graph has read none of them. They are laboratory chimeras and not endogenous t(4;11) products, so not a substitute for the index fusion - but a strictly better class of evidence than a wild-type KMT2A partner."
}defect 2 psicquic staleness
{
"measured_2026_09_22": {
"Q9UHB7_psicquic_rows": 179,
"Q9UHB7_psicquic_distinct_pmids": 23,
"Q9UHB7_psicquic_max_pmid": "39251607",
"Q9UHB7_psicquic_rows_from_40205054": 0,
"P48426_psicquic_rows": 234,
"P48426_psicquic_distinct_pmids": 17,
"P48426_psicquic_max_pmid": "39251607",
"P48426_psicquic_rows_from_40205054": 0,
"P48426_rest_indexed_interactions": 320,
"rest_rows_from_40205054": "present for both accessions"
},
"missing_publication": "PMID 40205054, Schaffer LV et al., Nature 2025 - joint biophysical interaction and immunofluorescence map of >5,100 proteins in U2OS, 275 molecular assemblies. A different laboratory, a different cell line and an orthogonal modality from BioPlex.",
"consequence_for_the_headline_number": "analyses/core-complex-interactome-gap/results.json reported 217 union partners, 89 with an entry (41.0%) and 119 absent; re-run after this tranche it gives 94/217 (43.3%), 112 absent, read queue 20 -> 15, denominator unchanged at 217. Either way it is computed against a mirror whose newest publication is from 2024, so numerator AND denominator are FLOORS and nothing in the results file says so.",
"which_way_the_error_runs": "The denominator is too small, so unnominated partners exist. The per-partner publications lists are too short, so a row that looks like one platform may have two: CAMKV, PIP4K2A and EPB41L1 each gain a publication between the PSICQUIC snapshot and the REST query. The brief's warning that a 2-paper row may rest on one platform is correct about what the queue can see and understates the evidence for three of this tranche's seven partners.",
"recommendation": "Move run.py to IntAct REST and CARRY BOTH NUMBERS with a banner, per this project's rule that an endpoint change must be announced as an instrument change rather than a corrected figure. Do not silently re-run.",
"also_found": "The PSICQUIC tab25 response carries only 15 COLUMNS, so experimental role, biological role and expansion method are unavailable from that endpoint entirely. A filter written against the 25-column MITAB spec drops every row and returns a clean zero - which this beat hit on its first sweep and corrected by printing the column count."
}defect 3 substring accession search
{
"measured_2026_09_22": {
"findInteractions/EBI-2620048 rows returned": 7,
"intact interactionCount for EBI-2620048": 6,
"spurious row": "S100B-NEDD8, interaction AC EBI-26200486, PMID 32814053",
"second instance": "SPATS1-SARS1 via EBI-26200754 on a query for EBI-2620075"
},
"control": "In a spurious row NEITHER participant is the queried interactor. Apply it to every accession-based IntAct query.",
"trend": "Will worsen: IntAct accessions have grown by an order of magnitude, so short early accessions are prefixes of long recent ones."
}recommended fixes in order of value
[ "Enumerate the four fusion-construct interactors explicitly as extra baits in analyses/core-complex-interactome-gap/run.py - they cannot be discovered by accession, so they must be named.", "Make gene_of() record an unresolvable partner in a named counter instead of dropping it silently.", "Make every interactome accession filter isoform-tolerant by stripping a trailing -N; measured cost of not doing so is CAMKV's 12 rows seen as 6 and 3 publications seen as 2.", "Move to IntAct REST and carry both numbers with a banner rather than correcting 89/217 in place." ]
- The 47 fusion-construct records are experiments on overexpressed laboratory chimeras in HeLa and HEK293T, so reading them will produce fusion-side evidence that is still two imports away from infant B-lineage KMT2A::AFF1 - and the temptation will be to quote them as 'measured on the fusion' without that qualifier.
- Moving run.py to IntAct REST will change the headline coverage figure in an uncontrolled direction, because the denominator grows with newly curated partners while the numerator grows only with partners that happen to have entries. The figure could fall while the graph gets strictly better, which is exactly what happened the last time this project changed an interaction endpoint.
- Recommending that unresolvable partners be counted rather than dropped will raise the 'absent entirely' figure, and a rising gap number after a beat whose job was to close gaps will read as a regression unless the instrument change is announced with it.
- This entry asserts that 47 records exist and enumerates 7. If the 40 unread records turn out to be redundant spoke expansions of a handful of pulldowns, the headline number in this entry's own title is inflated - and the title is what will be quoted.
- What are the 32 interactions on EBI-2890930, the MLL-AF9 fusion protein interactor? They were not enumerated here, they are the largest single body of fusion-side interaction evidence in IntAct, and reading them is one query.
- Are there fusion-construct interactors this beat's five name stems did not reach? Only mll_enl and mll_af9 returned records out of five stems tried, so a systematic sweep of IntAct interactors whose interactorXrefs list is empty would establish the true size of the blind spot.
- By how much does the 217-partner denominator grow when run.py moves from PSICQUIC to IntAct REST? Nobody knows, and the answer changes the PI's headline number in both the numerator and the denominator.
- How many partners in the 128-row all_missing list have their IntAct record split across isoform accessions, as CAMKV's is? Nothing in this project's interactome code is isoform-tolerant.
- Should a coverage analysis that cannot see a class of records report that class's size as a named zero? The deeper failure here is not that 47 records were missed but that nothing in the output said anything had been dropped.
- E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
IntAct holds four engineered MLL-fusion interactors - EBI-2890930 (MLL-AF9 fusion protein, 32 interactions), EBI-2620068 (mll_enl, 8), EBI-2620048 (mll_aff4, 6) and EBI-2620075 (mll_aff4-1, 1) - each with an EMPTY interactorXrefs list and an interactorPreferredIdentifier equal to its own IntAct accession; the six records on EBI-2620048 are MED19 once and MED26 four times from PMID 21729782 in HeLa, plus AFF1 once from PMID 20153263 in HEK293T, all anti-tag co-immunoprecipitation typed association.
IntAct REST findInteractor (mll_af9, mll_enl, mll_aff4_fusion, EBI-2620048, EBI-2620075) and findInteractions for each accession, with interactorXrefs, interactorPreferredIdentifier, interactionCount, experimentalRole, detectionMethod, hostOrganism and publicationPubmedIdentifier read per record; retrieved 2026-09-22 · IntAct molecular interaction database (EMBL-EBI) 2026What this evidence cannot show
Retrieved 2026-09-22 and the counts will move. The 32 interactions on EBI-2890930 and the 8 on EBI-2620068 were NOT enumerated for this entry - only EBI-2620048's six and EBI-2620075's one were read - so '47 records' is IntAct's own interactionCount summed, and the CONTENT of the 40 unread records is not claimed. The search for further fusion interactors used five name stems (mll_af4, mll_aff1, mll_fusion, mll_enl, mll_af9), of which two returned records, so the set of four is a floor and not an exhaustive enumeration. Every construct is an overexpressed laboratory chimera, so its partners are candidates for an endogenous fusion, not members of it.
Evidence that argues against this (1)
- A proteome-scale AP-MS interactome of the index fusion exists in the literature and has never been curated into IntAct at all, so the fusion-side evidence this entry recovers is a fragment of what exists rather than the whole of it - and an argument built on the scarcity of fusion-side records understates how much sits uncurated. Skucha A et al. 2018
- E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
Both of this repository's interactome gap analyses query by UniProt accession and resolve a partner's identity with a regex for a uniprotkb (gene name) alias token, so a fusion-construct interactor - whose MITAB alias field carries only psi-mi display names and no gene-name token - returns None from gene_of() and is dropped from the partner union, the read queue and the coverage denominator; and because PSICQUIC's search/query endpoint is free-text rather than id-scoped, the one MED19 record that does match is returned under BOTH the KMT2A and the AFF4 query, producing the read queue's MED19 n_baits of 2 for a single interaction against neither protein.
analyses/core-complex-interactome-gap/run.py - gene_of() regex on the MITAB alias field, PSICQUIC search/query/<accession>?format=tab25 endpoint; and the returned MITAB rows for query/Q03164 and query/Q9UHB7 showing interaction EBI-4321349 with alias field psi-mi:mll_aff4_fusion(display_short)|psi-mi:EBI-2620048(display_long); read and executed 2026-09-22 · This repository / IntAct PSICQUIC (EMBL-EBI) 2026What this evidence cannot show
This is a defect in a file this beat does not own and it is reported rather than edited. The double-attribution was diagnosed by dumping the raw MITAB rows for both bait accessions and observing the identical interaction accession EBI-4321349 in both, with column 1 reading intact:EBI-2620048 rather than any UniProt accession. Note the PSICQUIC tab25 response here carries only 15 columns, so experimental role and expansion method are NOT available from that endpoint at all - a filter written for the 25-column spec silently drops every row, which this beat also hit and corrected.
Evidence that argues against this (1)
- Dropping an unresolvable partner is defensible behaviour for a coverage metric, because a construct with no accession cannot be matched against a gene-<symbol> node id and counting it would inflate the denominator with something the graph could never cover. The defect is that the drop is SILENT and uncounted, not that it happens. This repository 2026
- E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
IntAct's PSICQUIC mirror is stale by at least a year: for AFF4 (Q9UHB7) it serves 179 rows over 23 distinct publications with a maximum PMID of 39251607 (2024) and ZERO rows from PMID 40205054, and for PIP4K2A (P48426) 234 rows over 17 publications with the same maximum PMID and again zero rows from 40205054 - while IntAct REST serves the 40205054 rows for both accessions.
IntAct PSICQUIC search/query/Q9UHB7 and /P48426 (format=tab25, maxResults=4000), all pubmed identifiers extracted per row, compared against IntAct REST findInteractions for the same accessions; run 2026-09-22 · IntAct molecular interaction database (EMBL-EBI) 2026What this evidence cannot show
Measured on two accessions, not on all six baits, so 'stale by at least a year' is established for these two and inferred for the mirror. A maximum PMID is a proxy for recency and not a release date - PMIDs are assigned at indexing, not at curation - so the claim is specifically that no PMID above 39251607 appears for either accession, which is what was measured. The two endpoints also differ in what they return per interaction: PSICQUIC tab25 here has 15 columns and no experimental-role field, REST has structured roles, so a row-for-row comparison of counts between them is not meaningful and only the publication sets were compared.
Evidence that argues against this (1)
- A PSICQUIC-versus-REST discrepancy could be an indexing lag on one accession rather than a systematic staleness, and the project's own rule about endpoint changes warns that switching endpoints changes every n unevenly between baits - so the right response is to carry both numbers rather than to treat the REST figure as the corrected one. IntAct molecular interaction database (EMBL-EBI) 2026
- E4established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
The publication missing from PSICQUIC is a genuinely independent platform: PMID 40205054 is a global map of human subcellular architecture built from joint measurement of biophysical interactions and immunofluorescence images for over 5,100 proteins in U2OS osteosarcoma cells, resolving 275 molecular assemblies - and three of the seven partners in this tranche (CAMKV, PIP4K2A, EPB41L1) gain a publication from it that the read queue does not list.
Multimodal cell maps as a foundation for structural and functional genomics. · Schaffer LV, Hu M, Qian G, Moon KM, et al. (34 authors; senior author Ideker T) · Nature 2025What this evidence cannot show
Independence here is of laboratory, cell line and modality, not of method class: this is still affinity purification with mass spectrometry on tagged proteins, so a systematic artefact of tagged-bait AP-MS would appear in it as in BioPlex. U2OS is an osteosarcoma line with no KMT2A rearrangement. The map assigns new functions to 975 proteins by integration rather than by direct test, so an individual row inside it is a model-generated hypothesis. Read as abstract and title; the assembly tables were not opened.
Evidence that argues against this (1)
- The same paper reports that its map decodes paediatric cancer genomes and implicates 102 validated new cancer proteins, which means rows inside it have been filtered through the authors' own integration and validation pipeline - so treating one row as an independent replication of a BioPlex row conflates a raw observation with a model output. Schaffer LV et al. 2025
- E5established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
The AFF1 record on the mll_aff4 fusion construct comes from the AF4/ENL/P-TEFb higher-order complex paper, an anti-tag co-immunoprecipitation in HEK293T, which is a focused complex purification rather than a proteome-scale screen.
A higher-order complex containing AF4 and ENL family proteins with P-TEFb facilitates oncogenic and physiologic MLL-dependent transcription. · Yokoyama A, Lin M, Naresh A, et al. (5 authors; senior author Cleary ML) · Cancer Cell 2010What this evidence cannot show
HEK293T with overexpressed constructs. This paper is already recognised in this repository as a focused complex purification rather than a screen - it is one of the five publications this project's own bait-supported-filter audit found misclassified as screen-like - so its appearance here adds a construct-side reading of a paper the graph already holds, not a new source.
Evidence that argues against this (1)
- Calling a paper a complex purification rather than a screen says what its authors set out to do and does not grade any single row inside it. This repository's own audit of that distinction hand-checked nine publications its heuristic had flagged as screen-like and found five of them misclassified, so the label is a useful provenance tag and a poor quality filter - a single construct-side row from PMID 20153263 should be read on its own method (overexpressed constructs, HEK293T, MI:0914 association) rather than on the paper's classification. This repository (IntAct-derived) 2026
- E6strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
IntAct's accession search matches by substring, so a query on EBI-2620048 returns 7 rows against an interactionCount of 6 - the extra being a S100B-NEDD8 row whose interaction accession EBI-26200486 contains the queried string - and the identifying control is that in a spurious row neither participant is the queried interactor.
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. · Haenig C, Atias N, Taylor AK, et al. (25 authors; senior author Wanker EE) · Cell Rep 2020What this evidence cannot show
The paper cited here is the source of the SPURIOUS row, cited so the artefact is identifiable rather than because its content bears on this analysis - it is a yeast two-hybrid neurodegeneration interactome and has nothing to do with KMT2A. Two collisions were observed (EBI-26200486 against EBI-2620048, EBI-26200754 against EBI-2620075), which is enough to establish the mechanism and not enough to quantify its frequency. The collision will become more common over time, because IntAct accessions have grown by an order of magnitude and short early accessions are prefixes of long recent ones.
Evidence that argues against this (1)
- Substring matching is also why the fusion-construct records are reachable at all - a strict identifier match on an interactor with no identifier would return nothing - so the permissive search is simultaneously the defect and the only route to the 47 records this entry is about. IntAct molecular interaction database (EMBL-EBI) 2026
the isoform-split and substring-match traps were found in the same sweep as the fusion-construct blind spot
the one fusion-construct record that leaked into the read queue is MED19's, and it was attributed to two baits it was not tested against
MED26 carries four of the six enumerated mll_aff4 construct records - more than any other protein
AFF1 is the third protein with a curated interaction against an mll_aff4 construct (PMID 20153263, HEK293T)
- related to →KMT2A::MLLT3 (MLL-AF9), t(9;11)(p21.3;q23.3)
IntAct's largest fusion-side body of evidence is 32 interactions on an MLL-AF9 construct (EBI-2890930), unread by this graph
- related to →KMT2A::MLLT1 (MLL-ENL), t(11;19)(q23;p13.3)
EBI-2620068 mll_enl carries 8 interactions against an MLL-ENL construct, also unread
the 89/217 figure is computed on a PSICQUIC mirror whose newest publication is from 2024; both numerator and denominator are floors
same accession-keyed gene_of() regex, so the same blind spot for fusion-construct interactors
PIP4K2A gains a third publication (PMID 40205054) that the PSICQUIC-based read queue cannot see