Oncofusion

start / graph / ana-q113-pride-holds-three-mll-af4-proteomes-so-the-junction-peptide-absence-now-has-accessions

Analysisstrong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.Q113-bounded-absence-audit

The junction-peptide absence was a claim about mass-spectrometry datasets bounded by a PubMed abstract search: PRIDE holds three human MLL-AF4 proteomics projects, so measured-not-searched is now named rather than asserted

also called Q113 PRIDE sweep · junction peptide archive bound

This project says nobody has ever reported the short piece of protein that straddles the join in a fusion protein. That statement was made by searching paper summaries, but the claim is about raw data files - and three sets of the right kind of raw data are sitting in the public proteomics archive.

The same thing, for a scientist

`absence-no-kmt2a-fusion-junction-peptide-reported-in-any-mass-spectrometry-dataset` is classed `measured-not-searched`, and its `not_swept` field names the step: *PRIDE/ProteomeXchange raw files from SEM, RS4;11, MV4-11 re-searched against a fusion-augmented database with 2 missed cleavages*. Its bound, however, is five PubMed `[tiab]` queries. Those establish that nobody has WRITTEN about a junction peptide; they say nothing about what is in the archive. This beat queried PRIDE Archive directly: keyword **MLL-AF4** returns **three** human projects - PXD043920 (MLL-AF4 with PAF1 and FACT at high-density enhancers, LTQ, 2023), PXD041875 (NG2 as an MLL-AF4 target gene in glucocorticoid-resistant infant MLL-r B-ALL, Orbitrap Eclipse, 2024) and PXD009338 (*Protein Interactions of 7 MLL-fusion Proteins*, LTQ Orbitrap Velos, 2018, already cited by this graph). Keyword **RS4;11** returns two more, of which PXD014711 (exosome proteomes from drug-tolerant MLL leukaemia cells) is on-topic-adjacent and PXD057859 is an MDM2-degrader study that merely names the line [E1][E2]. The absence **survives** - no junction peptide is reported anywhere - but its archive half is now a list of accessions with instruments and dates attached, which is the difference between a to-do and a task.

Go deeper
Why the instrument mismatch matters more than the count

A junction peptide is exactly the object rule 80 was written about: it would appear, if at all, in a supplementary identification table, never in an abstract. No widening of the query, no additional synonym and no MeSH term can reach it. The only instruments that can are (a) the archive itself and (b) a re-search of the raw files. This entry does (a). It does not do (b), and (b) is where the answer actually is.

The original entry's own control is the strongest thing in it and should be kept in view: "BCR-ABL"[tiab] AND ("junction peptide" OR "fusion peptide")[tiab] AND mass spectrometry[tiab] returns 0 as well. The most-measured fusion protein in medicine has no published junction-peptide identification either, which argues the absence is a field-wide convention rather than a KMT2A-specific gap - and that is a much stronger claim than the one the entry makes.

What the three projects can and cannot answer

PXD009338 is the most directly useful: it is an interaction proteome of seven MLL fusion proteins, so a fusion polypeptide was physically enriched and digested. If a junction peptide is anywhere in a public deposit, it is most likely in that one - and it has already been opened by this graph for a different purpose without a junction peptide being reported, which is weak evidence that the re-search will confirm the absence rather than overturn it 2.

PXD043920 and PXD041875 are chromatin- and target-gene-centred and were not designed to enrich the fusion, so a junction peptide there would be serendipitous. All three are LTQ- or Orbitrap-class instruments with published raw files, so the re-search is mechanically possible. None of the three is an infant-derived KMT2A::AFF1 line profiled for the fusion protein itself, which is the experiment the graph actually wants.

Facts and figures
scriptno script; PRIDE Archive v3 project search API, run inline 2026-09-22
statusrun
run date2026-09-22
run byQ113-bounded-absence-audit
absence testedabsence-no-kmt2a-fusion-junction-peptide-reported-in-any-mass-spectrometry-dataset
verdictSURVIVES. No junction peptide is reported. What changes is that its archive half is now enumerated.
instrument mismatchthe claim is about mass-spectrometry DATASETS; the bound was five PubMed [tiab] queries. PubMed cannot see a supplementary identification table (rule 80) and cannot see an archive at all.
what this does NOT dono raw file was downloaded and no re-search against a fusion-augmented database was performed. The step the original entry names remains unrun; it now has a starting list.
the strongest thing in the original entryits BCR-ABL control also returns 0 - the most-measured fusion protein in medicine has no published junction-peptide identification either, which makes this a field-wide convention rather than a KMT2A-specific gap
pride projects
[
  {
    "accession": "PXD043920",
    "title": "MLL-AF4 cooperates with PAF1 and FACT to drive high density enhancer interactions in leukemia",
    "organism": "Homo sapiens",
    "instrument": "LTQ",
    "public": "2023-08-18"
  },
  {
    "accession": "PXD041875",
    "title": "NG2 is a target gene of MLL-AF4 that underlies glucocorticoid resistance in infant MLL-rearranged B-ALL by regulating NR3C1 expression",
    "organism": "Homo sapiens",
    "instrument": "Orbitrap Eclipse",
    "public": "2024-07-12"
  },
  {
    "accession": "PXD009338",
    "title": "Protein Interactions of 7 MLL-fusion Proteins",
    "organism": "Homo sapiens",
    "instrument": "LTQ Orbitrap Velos",
    "public": "2018-05-25",
    "note": "already cited by this graph"
  },
  {
    "accession": "PXD014711",
    "title": "Drug-tolerant cell-derived exosomes regulate proteasome inhibitor resistance pathways in MLL leukemias",
    "organism": "Homo sapiens",
    "instrument": "LTQ Orbitrap",
    "public": "2020-05-26",
    "retrieved_by": "keyword RS4;11"
  },
  {
    "accession": "PXD057859",
    "title": "KT-253, A Novel MDM2 Degrader and p53 Stabilizer",
    "organism": "Homo sapiens",
    "public": "2025-05-07",
    "retrieved_by": "keyword RS4;11",
    "on_topic": false
  }
]
keyword counts
{
  "MLL-AF4": 3,
  "RS4;11": 2,
  "KMT2A": "at least 20 (first page)",
  "MV4-11": "at least 20 (first page)"
}
How this could bite us back
  • A junction peptide is the only direct proof the fusion protein exists, and every therapeutic argument in this graph assumes it does. If a properly powered re-search of three public deposits still finds nothing, that is not reassurance - it is a measurement that the protein is below the detection floor of ordinary proteomics, which has consequences for any modality that depends on presenting or binding the junction.
Still open
  1. Does a re-search of PXD009338 against a KMT2A::AFF1-augmented database with two missed cleavages recover a junction-spanning peptide? That is the experiment the original entry asked for and it is now a named, bounded compute task.
  2. Is the in-frame KMT2A::AFF1 junction tryptic peptide of usable length and charge at all? The original entry computed a target; reconciling that computation against the actual junction sequences would say whether a negative re-search means absent or undetectable.
  3. The BCR-ABL control returns zero too. Is there any fusion oncoprotein in any cancer for which a junction peptide has been reported by mass spectrometry, and if there is exactly one, what did that group do differently?
Every source behind this entry (2)
  1. E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    PRIDE Archive holds three human proteomics projects indexed under MLL-AF4 and two under RS4;11.

    What this evidence cannot show

    A keyword search matches project metadata, so a project that used an MLL-AF4 line without naming it would be missed, and a project naming it in passing is counted. PXD057859 is an MDM2-degrader study that only mentions the line and is counted here but is not on topic. No search of the raw files was performed.

    Evidence that argues against this (1)
    • The PRIDE keyword index is not a census of the MLL-fusion proteomics literature: keyword 'KMT2A' alone returns at least 20 projects on the first page, so the three-project figure is a bound on the string MLL-AF4 and not on the material available for a junction-peptide re-search. EMBL-EBI PRIDE Archive 2026
  2. E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.dataset

    One of the three is an interaction proteome of seven MLL fusion proteins, so a fusion polypeptide was physically enriched and digested in a public deposit.

    What this evidence cannot show

    The project title asserts fusion-protein interaction proteomics; whether the affinity handle was on the fusion itself or on a partner, and whether the fusion polypeptide was recovered at all, was not checked by this beat and would decide whether a junction peptide could even be present.

    Evidence that argues against this (1)
    • A tag-based pulldown of a fusion protein enriches the bait, but a junction peptide is only observable if the tryptic peptide spanning the junction is of usable length and charge and is in the search space. A negative from a re-search of PXD009338 would therefore be a bound on that peptide's detectability in that experiment, not on its existence. EMBL-EBI PRIDE Archive 2018
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