Oncofusion

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Analysisstrong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.Q142-aff1-in-primary-infants

The pre-registered magnitude test failed because the statistic was bounded by construction - top-decile share spreads only 1.1-1.4x between samples and cannot express what the published oncoprotein score says varies

I planned to test whether the strength of the fusion's binding differs between patients, using a measure that turned out to be incapable of showing a big difference even if one existed. The test is reported as void rather than as a negative result.

The same thing, for a scientist

**Pre-registered outcome B1** was that between-sample rank ordering would agree (rho >= 0.7) while the magnitude of enrichment would differ by >= 1.5-fold, reproducing the project's standing claim that ordering transfers and magnitude does not. **Measured spread of the top-decile share** - the share of a sample's total promoter signal that falls in its own top 10% of promoters [E1]: | factor | max/min across samples | |---|---:| | H3K4me3 | 1.11x | | IgG | 1.11x | | ENL | 1.14x | | KMT2A-N | 1.21x | | DOT1L | 1.29x | | AFF1 | 1.36x | **Not one factor reaches the pre-registered 1.5x, so B1 fails - and the failure is mine, not the data's.** The top-decile share is bounded below by 0.1 and above by 1 by construction, and in practice it sits between 0.27 and 0.85 in every track here. A statistic with that little room cannot register the kind of between-sample variation the source paper reports, which it measures with a per-interval oncoprotein score that has no such ceiling [E2]. **There is no spike-in in this deposit, so no unbounded magnitude statistic was available to me** - the depth-free alternatives are all shares. **Recorded as a void test rather than a negative one.** Reporting 'magnitude transfers between infant samples' from these numbers would be a claim about the metric's ceiling. The project's standing 'ordering transfers, magnitude does not' is neither confirmed nor refuted here.

Go deeper
What would actually test it

A spike-in-normalised or occupancy-per-cell measurement, or the paper's own Bayesian oncoprotein score recomputed from the fragment BEDs, which are deposited. The second is feasible from this deposit and was not attempted in this beat: it needs the peak intervals and the read-count model, not the bigWig means used here.

Facts and figures
scriptanalyses/q142-aff1-in-primary-infants/analyze.py
statusrun
result summaryB1 magnitude criterion not met; test declared void because the statistic is bounded.
pre registered outcomeB1 VOID
Still open
  1. Can the paper's oncoprotein score be recomputed from the deposited fragment BEDs, giving this corpus an unbounded between-sample magnitude statistic for primary infant material?
Every source behind this entry (2)
  1. E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.dataset

    The between-sample spread of top-decile promoter share in GSE252378 is 1.11-1.36-fold for every factor measured, below the 1.5-fold threshold pre-registered for a magnitude difference.

    GSE252378 - AutoCUT&RUN and AutoCUT&Tag profiles of 36 MLL-rearranged leukemia samples (171 GSMs, hg38) · Janssens DH, Henikoff S (Fred Hutchinson Cancer Center / Van Andel Institute) · NCBI Gene Expression Omnibus 2024
    What this evidence cannot show

    The statistic is bounded in [0.1, 1] by construction, which is the point of this entry. Computed from within-sample promoter shares; no spike-in exists in the deposit.

    Evidence that argues against this (1)
    • A bounded statistic is not necessarily an insensitive one - a 1.36x spread in a quantity confined to [0.27, 0.85] is a substantial relative move, and a reader could argue B1 was correctly scored as failing rather than void. The reason for voiding it is the mismatch with the paper's unbounded score, not the bound alone. Janssens DH et al. 2024
  2. E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper

    The source paper measures between-sample variation in oncoprotein enrichment with a Bayesian per-interval oncoprotein score derived from N- and C-terminal read shares, and reports that enrichment is highly variable between samples.

    MLL oncoprotein levels influence leukemia lineage identities · Janssens DH, Duran M, Otto DJ, Wu W, Xu Y, Kirkey D, Mullighan CG, Yi JS, Meshinchi S, Sarthy JF, Ahmad K, Henikoff S · Nature Communications 15:9341 2024
    What this evidence cannot show

    The score is itself built from read shares within each library and so is also depth-normalised; it is unbounded per interval but is not an absolute occupancy measurement either.

    Evidence that argues against this (1)
    • Because the oncoprotein score is also a within-sample share at its base, the paper's variability claim is not an absolute-occupancy claim either, and neither instrument in this comparison can say how many fusion molecules are on a promoter in a patient. Janssens DH et al. 2024
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