Oncofusion

start / graph / ana-q120-the-q118-function-arm-falsifier-does-not-fire-in-rs4-11-and-fires-in-molm13

Analysisstrong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.Q120-h3k79me2-second-line-and-the-mll1-epitope

A falsifier written and scored inside Q118 last cycle, cashed again in the second cell line one cycle later: H3K79me2 at the MLL1-N held bins is 0.7008 in RS4;11 (does not fire, threshold 0.75) and 0.9980 in MOLM13 (FIRES) - the same pre-registered clause, opposite verdicts, and nothing in the clause names a cell line

also called the function arm falsifier, second line · a falsifier that flips between lines

Last cycle a prediction was written down in advance: if the histone mark stays above a stated level after the drug, then saying the protein complex is 'decoupled' understates what survives. In the first cell line the mark fell and the prediction did not trigger. In a second line the mark does not move at all and it triggers outright.

The same thing, for a scientist

**The falsifier, quoted from `hyp-q118-the-drug-removes-menin-and-leaves-an-mll1-n-complex-at-the-fusions-own-sites` as stored:** *H3K79me2 share ratio at the 1,390 RS4;11 MLL1-N held bins ABOVE 0.75 means the mark does NOT fall and 'decoupling' understates what survives.* | | RS4;11 (Q118) | MOLM13 (this beat) | |---|---:|---:| | H3K79me2 share ratio at the MLL1-N held set | 0.7008 | **0.9980** | | the track's genome-wide mid-occupancy floor | 0.9851 | 0.9899 | | floor-normalised | 0.7114 | **1.0082** | | threshold 0.75 | **DOES NOT FIRE** | **FIRES** | Same clause, same antibody lot, same drug and dose, same series, same instrument, same construction of the held set, one cycle apart. The clause names *the 1,390 RS4;11 MLL1-N held bins* and so is scoped to RS4;11 on a strict reading - but nothing in its logic is, and the conclusion it attaches to ('decoupling understates what survives') is a statement about menin inhibition, not about RS4;11. **What this costs the hypothesis.** `hyp-q118` says the drug removes menin and leaves an MLL1-N complex that has lost its function. In RS4;11 that reading survived because the mark fell to 0.70 while occupancy stayed at 1.04 over floor. **In MOLM13 occupancy stays at 1.036 over floor AND the mark stays at 1.008 over floor** - so in that line the retained material is not measurably decoupled from its own functional output at all, on this readout. The hypothesis is not refuted; its central adjective is.

Go deeper
This is reported, not applied

Rule 96 half two says that when a falsifier is answered the outcome is written INSIDE the falsifier, with a leading ALL-CAPS status phrase and without deleting the original text. hyp-q118-... is owned by another beat and the standing instruction is to report errors and updates in files I do not own rather than edit them.

Proposed appended text, for the coordinator to apply verbatim:

FIRES IN A SECOND CELL LINE, CYCLE 77 (Q120). The same clause scored in MOLM13 (KMT2A::MLLT3), GSM3635687/88, same series, same instrument: H3K79me2 at the 1,389 MOLM13 MLL1-N held bins is 0.9980, floor-normalised 1.0082, against the threshold of 0.75. In RS4;11 it was 0.7008 and did not fire. The clause is scoped to RS4;11 by its own wording and the conclusion it carries is not.

And the reagent clause the falsifier still lacks, which is why it fires without settling anything: CST #5427 anti-H3K79me2 reads a histone MARK, i.e. a consequence. It cannot distinguish halted deposition from active demethylation from replicative dilution, and it cannot attribute any of them to the fusion.

Two falsifiers, two cycles, two different failure modes

Cycle 76's registry row was that a pre-registered, scoreable, cheap falsifier can fire and still be unable to answer its own question, because the antibody in its own text is blind to the distinction the hypothesis is about. That was hyp-q117's human arm.

This is the adjacent failure: a falsifier whose numeric clause is perfectly scoreable and whose SCOPE is not stated. It names a bin count, a cell line, a mark, a threshold and a direction - everything rule 96 half one asks for - and it still gives opposite verdicts one cycle apart, because which cell lines the clause is meant to govern was never written down. A falsifier that fires in one line and not another is only informative if the hypothesis says in advance how many lines it claims.

The cheap fix, offered as a convention rather than a rule: a falsifier states its population, not just its instance - 'in any human KMT2A-rearranged line' or 'in RS4;11 specifically' - because those are different hypotheses and this one turned out to be the second while reading like the first.

Facts and figures
scriptanalyses/q120-h3k79me2-second-line-and-the-mll1-epitope/addendum-rank-and-crossline.py
statusrun
result summaryhyp-q118's FUNCTION ARM falsifier: RS4;11 0.7008 DOES NOT FIRE; MOLM13 0.9980 FIRES. Threshold 0.75 in both.
falsifier owner entryhyp-q118-the-drug-removes-menin-and-leaves-an-mll1-n-complex-at-the-fusions-own-sites
edit requested not appliedtrue
epigenetic readoutH3K79me2 (CST 5427) at the MLL1-N held set, two cell lines
shown for fusionKMT2A::MLLT3 in MOLM13 (fires) and KMT2A::AFF1 in RS4;11 (does not fire); neither reagent distinguishes the fusion from wild-type MLL1
absence classmeasured-not-analysed
absence class noteThe falsifier was unscoreable in a second line only because nobody had binned GSM3635687/88, public since 2019 in GSE127507 and excluded from the depositors' own processed table. Two downloads closed it.
absence class assigned2026-09-23 (Q120)
How this could bite us back
  • If a pre-registered clause can give opposite verdicts in two cell lines of the same disease family, then every single-line falsifier in this corpus - which is nearly all of them - is reporting a property of its line as a property of the mechanism, and no audit distinguishes the two.
Still open
  1. Does the graph want a `falsifier_population` field? 624 stated falsifiers, 17 recorded outcomes, and this is the first one measured to flip between systems. A one-line population clause would have made the flip a prediction rather than a surprise.
  2. Would the falsifier fire in ML-2 (KMT2A::AFDN)? GSE127507 has no H3K79me2 sample for that line, so the third partner cannot score it, and that is the cheapest way to tell a partner effect from a lineage effect.
Every source behind this entry (1)
  1. E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.dataset

    The FUNCTION ARM falsifier of hyp-q118, threshold 0.75, is 0.7008 (floor-normalised 0.7114) at the 1,390 RS4;11 MLL1-N held bins and 0.9980 (floor-normalised 1.0082) at the 1,389 MOLM13 MLL1-N held bins, both measured at 2 kb genome-wide bins from the deposited .deduped.tdf files of GSE127507 with within-sample shares.

    What this evidence cannot show

    The RS4;11 half is Q118's stored measurement re-read from its committed function-arm.json, not re-derived by me; the MOLM13 half is mine. NO SPIKE-IN NORMALISATION. All 26 GSE127507 records state a Drosophila spike-in was run, measured, and deliberately not used, and no scale factor is deposited; no GSE260742 record contains spike-in vocabulary at all. Every cross-condition number here is therefore a WITHIN-SAMPLE share or rank, which cancels the unknown per-sample scale factor exactly. No raw fold change is reported as a biological quantity anywhere in this beat. n = 1 per antibody per condition per line in both series. No number in this beat carries a spread and none is precise. CST #5427 anti-H3K79me2 reads a histone MARK, i.e. a consequence. It cannot distinguish halted deposition from active demethylation from replicative dilution, and it cannot attribute any of them to the fusion. Bethyl A300-086A, deposited as 'anti-MLL1n', an MLL1 N-TERMINUS epitope. The N-terminus is retained in every KMT2A fusion, so this track is the sum of the fusion and wild-type MLL1 in unknown proportion and CANNOT distinguish them. The immunogen residue range was not verified: three vendor routes were tried this session (fortislife.com two URL forms, bethyl.com/product/A300-086A) and all returned HTTP 404, so 'N-terminus' rests on the depositors' own target label and on the standard fact that MLL-FPs lack the C-terminal SET domain.

    Evidence that argues against this (1)
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