pbcheck audit report

1. Header

pbcheck audit of 'scaled_liver_atlas.h5ad'

pbcheck 0.1.0, generated 2026-09-01T12:00:00Z.

Status: naive_only (no counts matrix passed the raw-count check)

This is a pbcheck v0.1.0 audit of one stratum of one file. It measures how a naive per-cell test and a donor-pseudobulk test behave on this data under a donor-permutation null. It is run outside pbcheck's pre-registered Phase 0 protocol, is not a Phase 0 measurement, and makes no claim about any publication or about whether any reported result is true.

2. Read-out

Under donor permutation, with no true signal to find, the naive per-cell test calls a median of 41 genes (0.5% of the 6120-gene universe; Monte-Carlo SE 0.63) over 1000 permutations; on the real labels it calls 63. Both counts are corrected over the whole universe on their own (solo BH).

The naive arm's inflation factor lambda is 3.21 (IQR 0.44): above the band 0.9 to 1.1, which is the donor-pseudobulk arm's band, shown here to describe the naive number and not as the naive arm's own criterion.

The donor-pseudobulk arm was not run: no counts matrix passed the raw-count check.

11 donors in 'lupus_nephritis', 10 in 'healthy'; 352716 distinct donor splits exist.

Real-label calls over the permutation floor: the per-cell arm calls 1.54 times its own floor, both counts corrected over the whole universe on their own (solo BH).

Amendment 3 declares an operating envelope for the pseudobulk arm on synthetic oracles. For each donor-variance point it states the donor count per group at which the power target is reached, and each row says what the committed grid supports there: a point measured on the grid, or a count derived or extrapolated from it.
sigma_donor 0.2: at least 4 donors per group (power at least 0.6 at log2FC 1.0 in 200 genes; grid support 'not in the grid; Amendment 1 frontier only')
sigma_donor 0.35: at least 8 donors per group (power at least 0.6 at log2FC 1.0 in 200 genes; grid support 'ebayes power 0.793 at 8v8 (calibrated) -> n* <= 8')
sigma_donor 0.5: at least 13 donors per group (power at least 0.6 at log2FC 1.0 in 200 genes; grid support 'ebayes power 0.486 at 12v12, the largest n tested -> n* > 12')
sigma_donor 0.7: at least 23 donors per group (power at least 0.6 at log2FC 1.0 in 200 genes; grid support 'ebayes power 0.003 at 8v8 -> n* far above 8')
The arm's calibration was evaluated at one hard regime (sigma_donor 0.5, 8 against 8 donors) and nowhere else. pbcheck does not estimate sigma_donor for real data, so whether this stratum lies inside that envelope is not determined here.
Everything in this report is a diagnostic of this file: the naive arm's inflation factor and permutation floor, the pseudobulk arm's inflation factor, floor and false-positive rate as its negative control, and the bookkeeping of the shared gene universe. None of it is a Phase 0 result, and pbcheck does not rate this file against the Phase 0 decision rule.
The count matrix failed the raw-count check ('3812 of 4,000,000 scanned values are not integers'). The pseudobulk arm was dropped, never rounded, so this run has no negative control. The naive arm was run on the matrix as found, with the naive pipeline's own normalisation and log transform applied on top of it; its numbers describe that pipeline on this matrix and are not comparable to a run on raw counts.
No cell type was selected, so all cells were pooled into one stratum; the file has a column that looks like a cell-type annotation ('cell_type'). Pooling mixes composition shifts between conditions into the contrast; rerun with --celltype 'cell_type' --celltype-value <level> for a per-cell-type audit.

3. What these words mean

lambda: the genomic inflation factor: the ratio of observed test statistics to the null expectation, with 1.0 meaning no inflation.

permutation floor: the number of genes a test calls under donor permutation, when condition labels carry no real signal; it is the test's own false-positive baseline on this data.

donor-permutation null: the null distribution built by reassigning condition labels between donors, keeping every donor's cells together, and rerunning the test on each reassignment.

gene universe: the fixed set of genes both arms are tested and corrected over, frozen before either arm sees the real labels.

replication unit: the unit whose independent draws the statistics assume; for donor data that unit is the donor, not the cell.

thin-donor filter: the rule that drops a donor's pseudobulk profile when it is built from too few cells or too few counts, rather than keeping a noisy profile.

operating envelope: the region of donor count and donor-to-donor variability that Amendment 3 declares for the pseudobulk arm on synthetic data; each of its points states the donor count per group at which the power target is reached, on the committed grid or by the derivation the grid support of that point names.

sigma_donor: a knob of pbcheck's synthetic simulator for how much donors differ from each other; it cannot be measured on your data, which is why the envelope question is left open.

Monte-Carlo SE: the standard error of a quantity estimated from a finite number of permutations; it shrinks as more permutations are drawn.

BH convention (solo vs paired): solo BH corrects an arm's p-values over the whole gene universe on its own; paired BH corrects both arms together over the genes common to both, so their real-label counts are directly comparable.

4. Design audit

Donors per group
groupdonors (pre-filter)pseudobulk profiles (post-filter)
lupus_nephritis11n/a
healthy10n/a
Cells per donor (top 20 of 21; 1 more not shown)
donorcells
donor_00620
donor_01605
donor_02590
donor_03575
donor_04560
donor_05545
donor_06530
donor_07515
donor_08500
donor_09485
donor_10470
donor_11455
donor_12440
donor_13425
donor_14410
donor_15395
donor_16380
donor_17365
donor_18350
donor_19335

No batch columns were provided.

Design flags
FieldValue
donor nests in conditionTrue
imbalance ratio1.07
usable for pseudobulkTrue
flagsnone
Dropped cells
FieldValue
dropped, other condition1500
dropped, other cell type600
dropped, missing donor90
dropped, missing condition40
dropped, missing cell type20

5. Counts check

Counts check
FieldValue
sourcen/a
passedFalse
reason3812 of 4,000,000 scanned values are not integers
dtypefloat32
values scanned4000000

Examples of the values checked: 0.0, 1.34, 2.71, 0.0.

6. Naive per-cell arm

Real-label counts
FieldValue
real-label calls, solo BH63
Top genes, naive arm
genepvalpadjlog2fcpct grouppct reference
GOLGA8A2.1e-060.000141.8371.222.5
<b>3.4e-050.00089-1.211244.3
TXN29e-050.00190.9755.530.1
Naive inflation factor
FieldValue
lambda3.21
lambda IQR0.44
classabove_band
Solo permutation floor
FieldValue
median count41
median fraction0.005
IQR count12
bh modesolo
Monte-Carlo SE0.63

The paired floor is not shown: the pseudobulk arm left 6120 genes without a value, so a paired correction over the two arms would not cover the same genes; the solo floor above stands alone.

Permutations, naive arm
FieldValue
requested1000
achieved1000
Machinery check of the permutation engine, not a criterion of any kind: the inflation factor of the empirical permutation p-values is 1.02.

7. Donor-pseudobulk arm

Donor-pseudobulk arm: not run, because no counts matrix passed the raw-count check.

8. Shared universe bookkeeping

Frozen gene universe
FieldValue
size6120
minimum size200
buildernaive_detection_fallback

Builder rule: a gene is kept when it has a value greater than 0 in at least one cell of at least half the donors, computed on the matrix as found; no count-sum rule applies to a non-integer matrix

Thin-donor filter: not run.

Shared universe, real-label bookkeeping
FieldValue
common tested0
dropped for fairness0
no value in naive arm0
no value in pseudobulk arm6120
pseudobulk arm complete for every geneFalse
Real split against the permutation range
FieldValue
real split inside permutation rangen/a
real split percentile in permutationsn/a

9. Settings and provenance

Tool settings
settingvalue
n_perm_requested1000
n_perm_pb_requested200
seed0
top_n20
design_onlyno
naive_methodwilcoxon
naive_enginefast
pseudobulk_methodmoderated_ebayes
trendno
min_donors_per_group3
universe_min_total_count15
universe_min_prop0.5
fallback_universe_min_prop0.5
fallback_universe_min_size200
min_profiles_per_group_after_thin_filter3
Protocol constants
protocol constantvalue
alpha0.05
lambda_band[0.9, 1.1]
min_universe_size200
min_cells10
min_counts1000
Operating envelope
sigma_donormin donors per groupgrid support
0.24not in the grid; Amendment 1 frontier only
0.358ebayes power 0.793 at 8v8 (calibrated) -> n* <= 8
0.513ebayes power 0.486 at 12v12, the largest n tested -> n* > 12
0.723ebayes power 0.003 at 8v8 -> n* far above 8
Package versions
packageversion
numpy1.26.4
scipy1.13.1
pandas2.2.2
anndata0.10.7
scanpy1.10.1
statsmodels0.14.2
decoupler1.7.0
pydeseq20.4.10
Platform
FieldValue
platformWindows-10-10.0.26200
python3.12.4
Runtime by stage
stageseconds
load3.1
prepare0.4
design0.2
counts0.6
pseudobulk_build1.8
universe0.3
real_label5.2
permutation_null30.9
render0.2
The engine was measured on one synthetic oracle point (sigma_donor 0.5, 8 against 8 donors, 1500 genes), recorded in pilot/gate/synthetic_gate_2026-08-15.json; that measurement is not repeated on this file. Of the settings below, only the ones listed as protocol constants are pre-registered values taken from pbcheck.gate_config (alpha, lambda_band, min_universe_size, min_cells, min_counts); the permutation counts, the universe filter parameters, the fallback universe rule and the display settings are the tool's own and are not protocol values.

10. Footer

Generated by pbcheck 0.1.0. Protocol: docs/PHASE0_SPEC.md and docs/AMENDMENTS.md in the pbcheck repository.