Oncofusion

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

The measurement q148 called the one thing that could overturn its headline: scored as ~20 kb intervals instead of 2 kb promoters, the authors' GMP-like class is enriched in 0 of 24 untreated non-circular samples, while the two control classes reach 19 and 10 - so the promoter window was not the limitation

also called AML_specific 0 of 24 at interval scale · interval scoring does not rescue the GMP class · 62-66% of the GMP signal was already promoter-visible

A previous beat found no sign of a progenitor gene programme, and its own best objection was that it had only looked at narrow windows around gene starts. Looking at the full wide regions the original authors defined gives the same answer, while two comparison sets behave as expected.

The same thing, for a scientist

Q148 returned NEITHER on whether the HOXA-negative blasts carry the authors' GMP-like programme, and named its own best objection as **the cheapest remaining gap and "the one measurement that could overturn the headline"**: it had scored **2 kb promoters of annotated genes**, while the authors' peaks have a **median width of 19,943 bp**, so a signal in gene bodies or enhancers would be invisible. Q150 ran the interval-scale version across all 27 samples and **died on the session limit before reporting it.** **Design: interval scale, genome-wide 5 kb fragment-count bins, leave-the-sample-out coverability, 10000 draws, seed 1500150.** | class | intervals scored | enriched, untreated non-circular | |---|---:|---:| | `Oncoprotein_Target` *(control)* | 677 | **19 of 24** | | `ALL_specific` *(control)* | 20 | **10 of 24** | | **`AML_specific`** *(the GMP-like class)* | 33 | **0 of 24** | 🔵 **The controls make the zero a measurement.** The canonical oncoprotein-target class is enriched in **19 of 24** samples and the B-lineage class in **10 of 24**, on the same intervals, the same null and the same samples. **The instrument works; the GMP-like class is simply not enriched anywhere** [E1]. 🟠 **And the width rationale was weaker than it looked.** Q150's direct test of it (M1b) measured what fraction of each class's signal a promoter window can actually see. For `AML_specific` that fraction is **0.62-0.66** - so a 2 kb window was already capturing roughly two thirds of the class's signal, and the ~20 kb intervals were never hiding most of it [E1]. 🔴 **So q148's NEITHER verdict is confirmed by the test q148 itself nominated to overturn it.** The GMP-like destination is not there at promoter scale and not there at interval scale, with working positive controls at both.

Go deeper
The reagent shrinks at interval scale, and that is a real limit

The interval-scale class sizes are smaller than the promoter-scale ones q148 used: Oncoprotein_Target 677 against q148's 827, ALL_specific 20 against 37, and AML_specific 33 against 40. Overlap with q148's universe is 595, 17 and 29 respectively.

So this is not simply a wider view of the same material - it is a different and in places thinner reagent, and a 33-interval class has correspondingly less power than a 40-promoter one. The zero should be read with that in mind. What protects it is the controls: the same shrinkage applies to Oncoprotein_Target, which still reaches 19 of 24.

Genome-wide, only 3.98% of the 5 kb bins used for the coverability null overlap a promoter, and 71 Oncoprotein_Target intervals were lost to zero-coverage bins. Both are declared in the result file rather than discovered afterwards.

Facts and figures
scriptanalyses/q150-the-authors-intervals-and-the-depth-matched-discriminator/m1c.py
statusrun
run date2026-09-24
written up bycoordinator, cycle 139, from the agent's result files after it died mid-beat
designinterval scale, genome-wide 5 kb fragment-count bins, leave-the-sample-out coverability
n draws10000
seed1500150
promoter overlapping bins PCT3.975
n scorable intervals1620
frac gmp signal promoter visible0.62-0.66 (M1b, one sample's libraries)
set sizes interval scale
ALL_specific20.0ALL_specific: 20AML_specific33.0AML_specific: 33Oncoprotein_Target677.0Oncoprotein_Target: 677
set sizes q148 promoter scale
ALL_specific37.0ALL_specific: 37AML_specific40.0AML_specific: 40Oncoprotein_Target827.0Oncoprotein_Target: 827
overlap with q148 universe
ALL_specific17.0ALL_specific: 17AML_specific29.0AML_specific: 29Oncoprotein_Target595.0Oncoprotein_Target: 595
lost intervals zero bins
ALL_specific0.000ALL_specific: 0AML_specific1.000AML_specific: 1Oncoprotein_Target71.0Oncoprotein_Target: 71
set sizes interval scale — the numbers behind the chart
{
  "Oncoprotein_Target": 677,
  "ALL_specific": 20,
  "AML_specific": 33
}
set sizes q148 promoter scale — the numbers behind the chart
{
  "ALL_specific": 37,
  "Oncoprotein_Target": 827,
  "AML_specific": 40
}
overlap with q148 universe — the numbers behind the chart
{
  "Oncoprotein_Target": 595,
  "ALL_specific": 17,
  "AML_specific": 29
}
enriched untreated noncircular
{
  "Oncoprotein_Target": "19/24",
  "ALL_specific": "10/24",
  "AML_specific": "0/24"
}
lost intervals zero bins — the numbers behind the chart
{
  "Oncoprotein_Target": 71,
  "ALL_specific": 0,
  "AML_specific": 1
}
measurements
[
  {
    "quantity": "samples in which the authors' AML_specific (GMP-like) class is enriched, interval scale",
    "value": 0,
    "unit": "count of samples",
    "subject": "the 33-interval AML_specific class against a width- and coverability-matched null",
    "universe": "24 untreated non-circular GSE252378 samples; the same test gives 19 and 10 for the Oncoprotein_Target and ALL_specific control classes"
  }
]
Still open
  1. Power: what effect size would a 33-interval class in 24 samples have detected? Without it, 0 of 24 bounds the programme loosely rather than excluding it.
  2. The class was defined in p279/p318, which are excluded as circular. Is there any independent definition of a GMP-like promoter set - from a normal haematopoiesis reference rather than from these patients - that could be scored without circularity?
Every source behind this entry (1)
  1. E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.

    Scored as intervals against a width-matched and coverability-matched null over 10000 draws, the authors' AML_specific class is enriched in 0 of 24 untreated non-circular GSE252378 samples, while Oncoprotein_Target reaches 19 of 24 and ALL_specific 10 of 24 on the same intervals and null; and a promoter window already captures 0.62 to 0.66 of the AML_specific class's signal.

    What this evidence cannot show

    Run by Q150 on 2026-09-24 (cycle 138) and written up by the coordinator in cycle 139 from the agent's result files after it died on the session limit; the coordinator did not re-run the scoring. The interval-scale classes are smaller than q148's promoter-scale ones (AML_specific 33 against 40), so power is lower, and only 29 of the 33 overlap q148's universe. p279/p318 are excluded as circular because the peak classes were derived in that pair. The 0.62-0.66 promoter-visible fraction is measured in one sample's libraries (M1b), not across the cohort.

    Evidence that argues against this (2)
    • A 33-interval class tested in 24 samples has limited power, and 0 of 24 is compatible with a real but small effect. The controls bound this only partly: Oncoprotein_Target has 677 intervals, twenty times more, so its success does not establish that a 33-interval class would have been detected had it been enriched. A power calculation against a stated effect size is the missing piece and was not done.
    • The GMP-like class was defined in the p279/p318 pair by the original authors, so excluding that pair as circular removes the samples where the class is by construction most likely to score. The zero across the other 24 is therefore a statement about transferability rather than about whether the programme exists at all.
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