Oncofusion

start / graph / ana-q135-the-first-measured-h3k79me2-same-condition-floor-is-four-times-tighter-than-h2ak119ubs-in-the-same-arm

Analysisweak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.Q135-the-clean-pair-and-the-two-uncomputed-mark-channels

The first same-condition H3K79me2 noise floor measured anywhere in this thread: 11.17% at D1 and 26.44% at the TOP 0.1% stratum, against 45.72% and 62.63% for H2AK119ub in the same arm, the same condition and the same pairing shape - 4.1x tighter. A mark floor transferred from H2AK119ub does not describe H3K79me2.

also called the first per-mark H3K79me2 floor · a transfer replaced by a measurement · marks do not share a floor

Until now the repeat-to-repeat wobble for one chemical tag on DNA was assumed to apply to the others. Measuring it directly for a second tag gives a number four times smaller, so the assumption was making that tag's results look far less reliable than they are.

The same thing, for a scientist

**Every mark floor in this thread has been transferred from H2AK119ub or imported from a factor ChIP.** This replaces one transfer with a measurement. **H3K79me2, MLLAF9 Control arm, rep1 (GSM8123373, `.filt.bam.tdf`) against rep2 (GSM8123387, bare `.tdf`), both Mar-2024 submission batch** - the `P_marker` shape, which is cycle 107's pairing shape: | stratum | TOP | D1 | D2 | D3 | D4 | D5 | D6 | D7 | D8 | D9 | D10 | |---|---:|---:|---:|---:|---:|---:|---:|---:|---:|---:|---:| | **H3K79me2 SGC** | 26.44 | **11.17** | 7.19 | 4.91 | 1.86 | 0.62 | 1.66 | 3.68 | 7.45 | 11.85 | 14.51 | | H2AK119ub SGC, same shape | 62.63 | **45.72** | 13.40 | 2.56 | 5.08 | 9.56 | 14.32 | 18.04 | 23.06 | 31.36 | 26.30 | | ratio | 0.42x | **0.24x** | | | | | | | | | | **Shape- AND condition-matched**, which is the strict comparison: H3K79me2's D1 floor is **0.24x** H2AK119ub's, i.e. 4.1x tighter. The pre-registered M1 outcome - mark-specific if any two shape-matched floors differ by more than 2x - **fires**. **The floor is U-shaped in coverage rank** for both marks: high at TOP and D1, minimal in the middle deciles (0.62% at D5 for H3K79me2), rising again at D10. A single global floor is the wrong instrument for either mark, which is cycle 107's P1 confirmed a third time.

Go deeper
Bounded by n = 1, and said plainly

Only one of the three H3K79me2 conditions survived the universe gate. H3K79me2/DMSO aborted at 93.76% track agreement and H3K79me2/VTP at 92.62%; both abort under the pre-registered gate too. So this floor is a single matched pair, not a distribution, and no spread, median or interval is reported for it. The comparison against H2AK119ub is made at the same condition (SGC0946 5 uM) so the n=1 does not also import a condition mismatch.

A second condition would be worth more than any reanalysis of this one. The cheapest route is the coverage-restricted universe question in the open questions below.

What this changes for the thread

Cycles 100-107 score H3K79me2 claims against a floor borrowed from H2AK119ub or from a factor ChIP. In the one place both are now measured, the borrowed floor is 4.1x too wide, which means H3K79me2 effects previously written off as within-noise may not be. That is the opposite direction from cycle 107's correction, and it is the direction that re-opens claims rather than closing them.

It does not mean H3K79me2 measurements are 4.1x more trustworthy in general - the floor is arm-dependent for H2AK119ub and nothing here shows it is not for H3K79me2.

THE RENORMALISATION BOUND, AND IT APPLIES TO EVERY NUMBER IN THIS ENTRY. Within-sample shares sum to 1 and GSE260742 has NO USABLE SPIKE-IN (Q117 verified zero hits for the entire spike-in vocabulary across all 419,824 characters of its 158 sample records, and no scale factor is deposited), so a purely local change leaks into every other stratum by arithmetic. A FLOOR COMPUTED THIS WAY CANNOT DISTINGUISH 'the bulk moved' from 'the peaks moved and the shares renormalised'. A TIGHTER NUMBER IS NOT THEREBY A CLEANER ONE.

Facts and figures
markH3K79me2
armMLLAF9 Control
conditionSGC0946 5 uM
rep1 gsmGSM8123373
rep2 gsmGSM8123387
pairing shapeP_marker (.filt.bam vs bare, same submission batch)
d1 ratio to h2ak119ub0.24
n conditions scored1
n conditions refused2
preregistered outcome firedM1 - mark-specific
floor PCT
D50.620D5: 0.62D111.2D1: 11.17D1014.5D10: 14.51TOP26.4TOP: 26.44
floor PCT — the numbers behind the chart
{
  "TOP": 26.44,
  "D1": 11.17,
  "D5": 0.62,
  "D10": 14.51
}
h2ak119ub same shape same condition
{
  "TOP": 62.63,
  "D1": 45.72
}
refusals
{
  "DMSO": "track agreement 93.76%",
  "VTP": "track agreement 92.62%"
}
Still open
  1. Does the H3K79me2 floor stay 4x tighter than H2AK119ub's in the NTvKO arm, where the H2AK119ub floor is itself 4x tighter? If the ratio holds across arms it is a property of the mark; if it collapses it is a property of this arm.
  2. Would restricting to bins both members cover at depth rescue the two refused conditions without changing the surviving one's floor? That is a single re-run and has not been done.
Every source behind this entry (1)
  1. E1weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.dataset

    In GSE260742's MLLAF9 Control arm under SGC0946 5 uM, the same-condition H3K79me2 floor |R-1| measured between GSM8123373 (.filt.bam.tdf) and GSM8123387 (bare .tdf), same Mar-2024 submission batch, is 26.44% at the TOP 0.1% stratum and 11.17% at D1, against 62.63% and 45.72% for H2AK119ub in the same arm, condition and pairing shape - a D1 ratio of 0.24x. The other two H3K79me2 conditions failed the universe gate at 92.62% and 93.76% track agreement and were refused.

    What this evidence cannot show

    n = 1 CONDITION. This is a single matched pair and not a distribution; two of three conditions were refused and the refusals are recorded with their percentages. THE H3K79me2 ANTIBODY IS NOT RESOLVED - the token `antibod` occurs zero times in GSE260742's 158 sample records - so the mark identity rests on the depositor's titles and filenames, which cycle 107 verified are self-consistent across all 30 H3K79me2-titled samples but which is self-consistency, not correctness. SYSTEM: murine MLL-AF9 (KMT2A::MLLT3) myeloid blood cells, Mus musculus, mm10, one lab, one deposit - NOT the infant B-lineage KMT2A::AFF1 disease this graph is about. n = 3 conditions per arm, one cell system; the spread across conditions is reported so stability is visible and IS NOT A CONFIDENCE INTERVAL. THE RENORMALISATION BOUND, AND IT APPLIES TO EVERY NUMBER IN THIS ENTRY. Within-sample shares sum to 1 and GSE260742 has NO USABLE SPIKE-IN (Q117 verified zero hits for the entire spike-in vocabulary across all 419,824 characters of its 158 sample records, and no scale factor is deposited), so a purely local change leaks into every other stratum by arithmetic. A FLOOR COMPUTED THIS WAY CANNOT DISTINGUISH 'the bulk moved' from 'the peaks moved and the shares renormalised'. A TIGHTER NUMBER IS NOT THEREBY A CLEANER ONE.

    Evidence that argues against this (2)
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