Datasets / DANDI:000630

DANDI:000630

Not yet verified

Human L1 patch-seq electrophysiology

electrophysiological Human 8.1 GB 210 files
  • 9 reproduced
  • 4 not reproduced
  • 1 blocked

Counted separately: 7 claims that also use data from outside the dataset.

  • 1 reproduced
  • 1 partially reproduced
  • 2 not reproduced
  • 3 blocked

Counted separately: 18 claims on data the paper deposited in other archives.

  • 3 partially reproduced
  • 15 blocked

Counted separately: 2 checks that the dataset is the data behind the paper.

  • 2 partially reproduced

Tested on dataset version 0.230915.2257

View on DANDI Paper JSON How to read outcomes

Claims

From the paper 10.1126/science.adf0805

Reproducing the human electrophysiology findings of Chartrand et al. (2023) from dandiset 000630 15

Notebook reproduce_chartrand_2023.ipynb

Reproduced9

  • ReproducedResults, L1 patch-seq pipeline and transcriptomic references, paragraph 4; Table S2names its codes from outside the dataset

    The human L1 patch-seq dataset has 250 cells passing transcriptomic quality, 194 with electrophysiology passing quality control and 71 reconstructed; by subclass, 96 LAMP5, 35 MC4R, 33 PAX6, 15 L1 VIP and 15 other cells have electrophysiology.

    All cells were filtered for transcriptomic (n=250) and electrophysiological quality (n=194), and a subset of neurons (n=71) with sufficient cell labeling were imaged at high resolution

    Results, L1 patch-seq pipeline and transcriptomic references, paragraph 4; Table S2

    194 cells of P in the ten L1 t-types; LAMP5 96, MC4R 35, PAX6 33, L1 VIP 15, other 15, as Table S2. The other 16 files of P are non-L1 t-types. The 250 and 71 counts need transcriptomes and reconstructions and are not tested.

    How the test differed from the paper’s method

    • Cell labels (t-type, subclass, layer, region, donor) come from the paper's cell table through the link claim dandiset-cell-link.
  • ReproducedResults, Morpho-electric diversity in human L1, paragraph 1; Figure 2Crests on an assumptionnames its codes from outside the dataset

    Human L1 subclasses differ in electrophysiology, notably in sag and initial firing rate (Kruskal-Wallis, FDR-corrected p < 1e-7).

    Electrophysiologically, subclasses were distinguished by subthreshold properties such as sag ... as well as several suprathreshold properties including firing rate ... Electrophysiological and morphological features distinguishing L1 subclasses (KW test, FDR-corrected p<10−7 for electrophysiology

    Results, Morpho-electric diversity in human L1, paragraph 1; Figure 2C

    What the paper reports

    • Kruskal-Wallis test, p < 10⁻⁷, FDR (Benjamini-Hochberg)-corrected (n = 96 LAMP5, 35 MC4R, 33 PAX6 and 15 L1 VIP cells (Table S2))

    Kruskal-Wallis across the four core subclasses (179 cells, 92 features). Sag has FDR p = 6.6e-20 (epsilon2 0.57). The initial firing rate at rheobase + 40 pA (first_isi_inv_hero) has FDR p = 4.7e-7 on the features computed here with the Methods' sweep QC, above the claim's 1e-7, and 1.7e-8 on the paper's own values (reading (b)), below it. 56 features have FDR p < 0.05. The computed initial firing rate differs from the paper's value by more than 1%, or has a value on one side only, in 28 of the 179 cells: 10 take another repeat of the same amplitude, 6 another amplitude, 10 have no sweep here that gives the paper's value and 2 have a value on one side only. In 11 cells of the test no sweep passing QC lies 39 to 61 pA above rheobase and IPFX falls back to a lower sweep; 6 of them disagree with the paper, and in 4 of these the paper's value comes from a sweep in range that fails here only the Methods' 500 ms rms noise criterion. Extracted without that criterion (variant a'), the features agree with the paper's values for more cells in 38 of 39 features, and first_isi_inv_hero has FDR p = 3.9e-9 (sag 3.3e-20), so the claim holds in full. The outcome rests on (a'), an assumption stated under deviations; with the criterion as written the claim is partially reproduced. The outcome was partially_reproduced through round 2 and was changed to reproduced after verification round 3. With any one donor left out, the largest uncorrected p is 3.1e-19 for sag and 3.5e-5 for the initial firing rate, on reading (a); this check was not run on (a').

    How the test differed from the paper’s method

    • Features follow the claims file's O1. Reading (a) uses the features computed here with IPFX 2.1.2 from the long square sweeps where they agree with the paper's aibs_features_E.csv within 1% for at least half of the cells (39 features, which agree within 1% for 53 to 98% of cells), and the paper's values for the others (custom features the paper did not release, ramp, short square and chirp features, and five adaptation ratios, which agree within 1% for only 4 to 37% of cells). Reading (b) uses the paper's values throughout. The 50% rule is an assumption of this attempt; the claims file's O1 does not say when a recomputed feature counts as computed. Two variants of reading (a) are shown, (a') with the features extracted without the Methods' 500 ms rms noise criterion, and (a, ratios) with the adaptation ratios computed here, for figs3a, fig6d and fig3g; neither changes an outcome except (a') for fig2c-subclass-ephys-differences, whose outcome rests on it.
    • Assumed that the paper's sweep QC did not exclude the sweeps that fail here only the Methods' rms noise criterion of 0.5 mV over 500 ms (Methods, Quality control) as IPFX measures it, so the outcome is judged on variant (a'), extracted without that criterion. This departs from the Methods' QC as IPFX measures it. The paper's own per-cell values were computed from such sweeps (7 of the 9 fallback cells that disagree with the paper), and without the criterion 38 of the 39 recomputed features agree with the paper's values for more cells (median share within 1% 0.933 against 0.895). With the criterion as written (reading a) the claim is partially reproduced (first_isi_inv_hero FDR p 4.7e-7); on the paper's values (reading b) it holds (1.7e-8). How the paper measured this noise is asked of the authors (findings, methods_unavailable).
    • Sweep QC follows the Methods as far as the files allow (leak within 100 pA, rms noise below 0.2 mV over 1.5 ms and 0.5 mV over 500 ms, IPFX's integrity check, and sweeps stored with zeros before the end of the stimulus left out); the Methods' criterion of a baseline within 2 mV of target is not applied, as the files do not state the target.
    • Dunn's post hoc tests as the Methods and legend say; the code's Mann-Whitney post hoc is computed as a variant.
    • Cell labels (t-type, subclass, layer, region, donor) come from the paper's cell table through the link claim dandiset-cell-link.
  • ReproducedResults, Morpho-electric diversity in human L1, paragraph 2; Figure 2B and 2Cquestion to the readernames its codes from outside the dataset

    LAMP5 cells show small sag and adaptation, PAX6 cells minimal sag and a high initial firing rate, while MC4R and L1 VIP cells show strong sag.

    Their electrophysiological phenotype was relatively undistinguished, with firing-rate adaptation and sag present but small ... along with minimal sag and high initial firing rate at the onset of response to depolarizing current injection ... MC4R cells had extremely compact ball-like axonal arbors, along with strong sag ... with a consistent stellate-like dendrite morphology and high sag

    Results, Morpho-electric diversity in human L1, paragraph 2; Figure 2B and 2C

    Parts (i) and (ii) hold under both readings and in variant (a'), with median sag MC4R 0.336 and L1 VIP 0.277 above LAMP5 0.116 and PAX6 0.051, PAX6 lowest. Part (iii) as amended holds under both readings and in (a'), as PAX6's median initial firing rate is 49.3 Hz, above LAMP5 (31.8 to 32.1 Hz) and MC4R (28.8 to 30.5 Hz) with Dunn FDR p of 3.4e-5 or less. What the answer changed. The first author run, before the reader's answer and before verification, tested part (iii) as PAX6 having the highest median of the four and recorded not_reproduced, since L1 VIP is higher (54.6 Hz; Dunn FDR p 0.39 to 1 between PAX6 and L1 VIP). Asked whether that read the paper's "high initial firing rate" correctly, a reader amended part (iii) to PAX6 above LAMP5 and MC4R (questions/000630.yaml), because the paper does not compare PAX6 with L1 VIP on this feature. Re-run on the amended criterion (author-answers), the claim is reproduced, the outcome both verification rounds reviewed; the notebook still prints the earlier part (iii), which fails.

    How the test differed from the paper’s method

    • Features follow the claims file's O1. Reading (a) uses the features computed here with IPFX 2.1.2 from the long square sweeps where they agree with the paper's aibs_features_E.csv within 1% for at least half of the cells (39 features, which agree within 1% for 53 to 98% of cells), and the paper's values for the others (custom features the paper did not release, ramp, short square and chirp features, and five adaptation ratios, which agree within 1% for only 4 to 37% of cells). Reading (b) uses the paper's values throughout. The 50% rule is an assumption of this attempt; the claims file's O1 does not say when a recomputed feature counts as computed. Two variants of reading (a) are shown, (a') with the features extracted without the Methods' 500 ms rms noise criterion, and (a, ratios) with the adaptation ratios computed here, for figs3a, fig6d and fig3g; neither changes an outcome except (a') for fig2c-subclass-ephys-differences, whose outcome rests on it.
    • Cell labels (t-type, subclass, layer, region, donor) come from the paper's cell table through the link claim dandiset-cell-link.
  • ReproducedResults, Morpho-electric diversity in human L1, paragraph 3; Figure S6A and S6B legendsnames its codes from outside the dataset

    No electrophysiological feature of human L1 cells differs with donor medical condition, sex or age after FDR correction.

    AP width (upper right) was the only significant electrophysiology feature (MW p=0.03, NS after FDR correction)

    Results, Morpho-electric diversity in human L1, paragraph 3; Figure S6A and S6B legends

    What the paper reports

    • AP width, epileptic against non-epileptic donors, before correction: Mann-Whitney test, p = 0.03
    • sex, the only feature before correction: Mann-Whitney test, p = 0.02

    A claim of absence on the paper's tests (194 cells, 92 features). Medical condition, epileptic against not, smallest p 0.0027 (sag, r = 0.43), smallest FDR p 0.19; sex, smallest p 0.011 (rheobase, r = 0.22), smallest FDR p 0.98; age, 36 features after the dropout filter, smallest p 0.039 (AP height at rheobase + 40 pA, rho = -0.15), smallest FDR p 0.43. No feature has FDR p < 0.05 under either reading. Two limits weaken the absence of an effect. The public table gives a medical condition for only 86 of the 194 cells (65 epileptic, 21 not), so the condition test has less power than the paper's. The dropout filter the criterion takes from the code leaves 56 of the 92 features out of the age test, sag and three adaptation ratios among them; without the filter no feature reaches FDR p < 0.05 for age either (smallest FDR p 0.73, sag p = 0.11). Variant (a') gives the same (smallest FDR p 0.19, 0.99 and 0.43).

    How the test differed from the paper’s method

    • The table's medical_conditions, donor_sex and donor_age stand in for the LIMS donor records the code reads, as the criterion says; 108 of 194 cells have no medical condition in the public table.
    • Features follow the claims file's O1. Reading (a) uses the features computed here with IPFX 2.1.2 from the long square sweeps where they agree with the paper's aibs_features_E.csv within 1% for at least half of the cells (39 features, which agree within 1% for 53 to 98% of cells), and the paper's values for the others (custom features the paper did not release, ramp, short square and chirp features, and five adaptation ratios, which agree within 1% for only 4 to 37% of cells). Reading (b) uses the paper's values throughout. The 50% rule is an assumption of this attempt; the claims file's O1 does not say when a recomputed feature counts as computed. Two variants of reading (a) are shown, (a') with the features extracted without the Methods' 500 ms rms noise criterion, and (a, ratios) with the adaptation ratios computed here, for figs3a, fig6d and fig3g; neither changes an outcome except (a') for fig2c-subclass-ephys-differences, whose outcome rests on it.
    • Cell labels (t-type, subclass, layer, region, donor) come from the paper's cell table through the link claim dandiset-cell-link.
  • ReproducedResults, Cross-species differences in L1, paragraph 2; Figure S6Cnames its codes from outside the dataset

    Some electrophysiological features of human L1 cells, including input resistance, vary with brain region; sparsely sampled regions either match MTG or have larger input resistance.

    We also explored dependence of L1 interneuron morpho-electric properties on brain region within our human data and found moderate effects on a set of features including dendrite extent and input resistance (Fig. S6C). For these features, more sparsely sampled regions either failed to differ from MTG cells or had smaller dendritic extent and larger input resistance

    Results, Cross-species differences in L1, paragraph 2; Figure S6C

    What the paper reports

    • Kruskal-Wallis test, p < 0.05, FDR-corrected

    Regions ITG (23 cells, 4 donors), MTG (115, 27), MFG (5, 3) and SFG (14, 5); 83 features, 6 with FDR p < 0.05. Input resistance (input_resistance_ss) has FDR p = 0.029; medians ITG 291, MTG 234, MFG 367, SFG 222 MOhm; no region is below MTG with Dunn FDR p < 0.05 (SFG against MTG p = 0.13; MFG above MTG, p = 0.0073). sag_peak_t, downstroke_rheo and avg_rate_max have FDR p 0.016 to 0.029. Variant (a') gives the same input resistance result (13 features with FDR p < 0.05 there).

    How the test differed from the paper’s method

    • input_resistance_ss is not computed here and is the paper's value under both readings.
    • Features follow the claims file's O1. Reading (a) uses the features computed here with IPFX 2.1.2 from the long square sweeps where they agree with the paper's aibs_features_E.csv within 1% for at least half of the cells (39 features, which agree within 1% for 53 to 98% of cells), and the paper's values for the others (custom features the paper did not release, ramp, short square and chirp features, and five adaptation ratios, which agree within 1% for only 4 to 37% of cells). Reading (b) uses the paper's values throughout. The 50% rule is an assumption of this attempt; the claims file's O1 does not say when a recomputed feature counts as computed. Two variants of reading (a) are shown, (a') with the features extracted without the Methods' 500 ms rms noise criterion, and (a, ratios) with the adaptation ratios computed here, for figs3a, fig6d and fig3g; neither changes an outcome except (a') for fig2c-subclass-ephys-differences, whose outcome rests on it.
    • Cell labels (t-type, subclass, layer, region, donor) come from the paper's cell table through the link claim dandiset-cell-link.
  • ReproducedFigure 4B legend; Results, Rosehip cells, paragraph 1names its codes from outside the dataset

    MC4R (rosehip) cells are distinguished from the rest of human L1 by strong sag and by irregular firing (Mann-Whitney, FDR p < 1e-4).

    Electrophysiological and morphological features distinguishing MC4R t-types (FDR-corrected MW test vs. rest of L1, p<10−4)

    Figure 4B legend; Results, Rosehip cells, paragraph 1

    What the paper reports

    • Mann-Whitney test against rest of L1, p < 10⁻⁴, FDR-corrected

    Reading (a) of the group (MC4R subclass, 35 of 210 Seattle strict-set cells, against the rest) gives sag median 0.336 against 0.118 (FDR p = 1.6e-18) and irregularity ratio 0.232 against 0.135 (FDR p = 1.2e-5), both higher and below 1e-4. Under reading (b) ADARB2 MC4R alone meets it (FDR p 3.1e-17 and 4.2e-6) and SST CHRNA4 alone does not (0.084 and 0.6). Variant (a') gives the same (FDR p 8.6e-19 and 1.2e-5).

    How the test differed from the paper’s method

    • The irregularity ratio (ir_late_mean) is custom code the paper did not release; it is the paper's value under both readings.
    • Features follow the claims file's O1. Reading (a) uses the features computed here with IPFX 2.1.2 from the long square sweeps where they agree with the paper's aibs_features_E.csv within 1% for at least half of the cells (39 features, which agree within 1% for 53 to 98% of cells), and the paper's values for the others (custom features the paper did not release, ramp, short square and chirp features, and five adaptation ratios, which agree within 1% for only 4 to 37% of cells). Reading (b) uses the paper's values throughout. The 50% rule is an assumption of this attempt; the claims file's O1 does not say when a recomputed feature counts as computed. Two variants of reading (a) are shown, (a') with the features extracted without the Methods' 500 ms rms noise criterion, and (a, ratios) with the adaptation ratios computed here, for figs3a, fig6d and fig3g; neither changes an outcome except (a') for fig2c-subclass-ephys-differences, whose outcome rests on it.
    • Cell labels (t-type, subclass, layer, region, donor) come from the paper's cell table through the link claim dandiset-cell-link.
  • ReproducedResults, Bursting PAX6 TNFAIP8L3 cells, paragraph 1; Figure 5Bnames its codes from outside the dataset

    PAX6 TNFAIP8L3 cells are distinguished from all other human L1 cells by a high initial firing rate at rheobase and an after-depolarization following the last spike.

    Both the initial firing rate at rheobase and the after-depolarization potential (ADP) following the final spike quantitatively distinguished PAX6 TNFAIP8L3 cells from all other L1 cells

    Results, Bursting PAX6 TNFAIP8L3 cells, paragraph 1; Figure 5B

    What the paper reports

    • Mann-Whitney test against rest of L1, p < 0.01, FDR-corrected (n = 2 PAX6 TNFAIP8L3 cells with electrophysiology (Table S2) against the rest of L1)

    Two PAX6 TNFAIP8L3 cells against 208. The initial firing rate at rheobase (computed here, equal to the paper's values) is 136 and 123 Hz against a median of 6.5 Hz (FDR p = 0.0081); the ADP slope (postap_slope_rheo, the paper's value) is 2.4 and 2.85 V/s against -0.43 (FDR p = 0.0051). Both are higher and below 0.01. The adp_deltav variant has FDR p = 0.07. Variant (a') gives the same (FDR p 0.0079 and 0.0051).

    How the test differed from the paper’s method

    • postap_slope_rheo and adp_v_last_rheo are custom features the paper did not release; they are the paper's values.
    • Features follow the claims file's O1. Reading (a) uses the features computed here with IPFX 2.1.2 from the long square sweeps where they agree with the paper's aibs_features_E.csv within 1% for at least half of the cells (39 features, which agree within 1% for 53 to 98% of cells), and the paper's values for the others (custom features the paper did not release, ramp, short square and chirp features, and five adaptation ratios, which agree within 1% for only 4 to 37% of cells). Reading (b) uses the paper's values throughout. The 50% rule is an assumption of this attempt; the claims file's O1 does not say when a recomputed feature counts as computed. Two variants of reading (a) are shown, (a') with the features extracted without the Methods' 500 ms rms noise criterion, and (a, ratios) with the adaptation ratios computed here, for figs3a, fig6d and fig3g; neither changes an outcome except (a') for fig2c-subclass-ephys-differences, whose outcome rests on it.
    • Cell labels (t-type, subclass, layer, region, donor) come from the paper's cell table through the link claim dandiset-cell-link.
  • ReproducedResults, Cross-modality relationships of L1 subclasses and t-types, paragraph 2; Figure 6D legendnames its codes from outside the dataset

    Two-cluster Gaussian mixtures on the best pair of electrophysiological features recover each subclass with F1 scores of 0.81 (LAMP5), 0.69 (MC4R), 0.89 (PAX6) and 0.5 (all others).

    F1 scores ... LAMP5 0.81, MC4R 0.69, PAX6 0.89, all others 0.5

    Results, Cross-modality relationships of L1 subclasses and t-types, paragraph 2; Figure 6D legend

    177 Seattle cells with soma in L1 (the depth table's layer, as clustering_classification.ipynb cell 16), 83 features, 3486 one- and two-feature subspaces per group. On the features computed here, Methods preprocessing (O3 a) gives best F1 LAMP5 0.785, MC4R 0.709, PAX6 0.896, all others 0.490; the code's preprocessing (O3 b) gives 0.806, 0.703, 0.892 and 0.526. On the paper's values alone the two give LAMP5 0.802 to 0.806, MC4R 0.693 to 0.712, PAX6 0.892 to 0.896 and all others 0.495 to 0.506. All are within tolerance; the closest to a bound is all others at 0.490 (floor 0.45). With the layer filled from the LIMS layer (189 cells, code preprocessing) the values are 0.840, 0.707, 0.879 and 0.494; in variant (a') 0.806, 0.703, 0.892 and 0.519; with the adaptation ratios computed here 0.825, 0.694, 0.892 and 0.511. Several best features are the paper's values (sag_tau, sag_peak_t, ramp and short square features).

    How the test differed from the paper’s method

    • Features follow the claims file's O1. Reading (a) uses the features computed here with IPFX 2.1.2 from the long square sweeps where they agree with the paper's aibs_features_E.csv within 1% for at least half of the cells (39 features, which agree within 1% for 53 to 98% of cells), and the paper's values for the others (custom features the paper did not release, ramp, short square and chirp features, and five adaptation ratios, which agree within 1% for only 4 to 37% of cells). Reading (b) uses the paper's values throughout. The 50% rule is an assumption of this attempt; the claims file's O1 does not say when a recomputed feature counts as computed. Two variants of reading (a) are shown, (a') with the features extracted without the Methods' 500 ms rms noise criterion, and (a, ratios) with the adaptation ratios computed here, for figs3a, fig6d and fig3g; neither changes an outcome except (a') for fig2c-subclass-ephys-differences, whose outcome rests on it.
    • Cell labels (t-type, subclass, layer, region, donor) come from the paper's cell table through the link claim dandiset-cell-link.
  • ReproducedResults, Cross-modality relationships of L1 subclasses and t-types, paragraph 2; Figure S8Anames its codes from outside the dataset

    A multi-class classifier assigns human L1 subclasses from electrophysiology with 82% cross-validated accuracy, balanced across subclasses.

    A multi-class classifier evaluated by cross-validation on the primary dataset had 82% accuracy balanced across subclasses

    Results, Cross-modality relationships of L1 subclasses and t-types, paragraph 2; Figure S8A

    164 Seattle cells of the four core subclasses with soma in L1 (depth table layer, as the code's cell 26). Accuracy with features common to all sites (72) is 83.5% with the Methods' preprocessing and 84.6% with the code's; with the 35 site-aligned features 79.7% and 78.8%. On the paper's values (reading b) and with the layer filled from the LIMS layer (176 cells) accuracy is 79.6 to 84.2%, and in variant (a') 79.4 to 85.0%. All are within 82 +/- 8.2. Balanced accuracy is 74.5 to 79.0%. The largest class is 52.4% of cells (54.0% with the filled layer) and balanced chance is 25%; the paper states no chance level.

    How the test differed from the paper’s method

    • Choosing features by site uses the Amsterdam and Szeged feature tables of the paper's code (tamas_features_E.csv, mansvelder_features_E.csv); those cells are not in the dandiset and are used only for this choice.
    • Repeated stratified 5-fold cross-validation with 10 repeats and seed 0 (scikit-learn defaults; the seed is a standard choice).
    • Features follow the claims file's O1. Reading (a) uses the features computed here with IPFX 2.1.2 from the long square sweeps where they agree with the paper's aibs_features_E.csv within 1% for at least half of the cells (39 features, which agree within 1% for 53 to 98% of cells), and the paper's values for the others (custom features the paper did not release, ramp, short square and chirp features, and five adaptation ratios, which agree within 1% for only 4 to 37% of cells). Reading (b) uses the paper's values throughout. The 50% rule is an assumption of this attempt; the claims file's O1 does not say when a recomputed feature counts as computed. Two variants of reading (a) are shown, (a') with the features extracted without the Methods' 500 ms rms noise criterion, and (a, ratios) with the adaptation ratios computed here, for figs3a, fig6d and fig3g; neither changes an outcome except (a') for fig2c-subclass-ephys-differences, whose outcome rests on it.
    • Cell labels (t-type, subclass, layer, region, donor) come from the paper's cell table through the link claim dandiset-cell-link.

Partially reproduced1

Not reproduced4

  • Not reproducedResults, Morpho-electric diversity in human L1, paragraph 1; Figure S3A legendquestion to the readernames its codes from outside the dataset

    Spike adaptation properties are strongly and inversely related to sag across human L1 cells (R2 = 0.74).

    Spike adaptation properties showed a strong inverse relationship with sag across the dataset (Fig. S3A)

    Results, Morpho-electric diversity in human L1, paragraph 1; Figure S3A legend

    What the paper reports

    • linear regression, R2 = 0.74, p < 10⁻¹³

    OLS of the upstroke adaptation ratio (third over first spike, the order that matches the paper's table) on sag with HC3 errors over 192 cells. In reading (a) the ratio is the paper's value (the ratio computed here agrees within 1% for 19% of cells and is not used) and sag is computed here: R2 = 0.334 (p = 1.3e-12). On the paper's values R2 = 0.359 (p = 3.3e-14), and in variant (a') 0.346, against 0.74 +/- 0.074. With both sag and the ratio computed here R2 is 0.204 (third over first, p = 1.6e-7) or 0.149 (first over third). All the paper's ratios are below 1 (0.38 to 0.97), so the upstroke falls from the first to the third spike, and the slope is negative (-0.61 in reading (a), -0.64 on the paper's values): cells with more sag have a larger fall, so more change, the opposite of the direction the criterion states. The paper says only inverse relationship, which a negative slope matches; whether the criterion misreads the paper is asked of a reader (questions/000630.yaml), and it cannot change the outcome, which fails on R2. On the medians of the ten t-types R2 is 0.28 to 0.31. The paper's own per-cell values with the code's regression do not give 0.74 either.

    How the test differed from the paper’s method

    • The adaptation ratio is computed here on the lowest long square with at least 4 spikes (Methods); it agrees with the paper's value within 1% for 19% of cells (median difference 2.7%), so reading (a) uses the paper's ratio with sag computed here, and the regression on the ratio computed here, in both orders, is a variant.
    • Features follow the claims file's O1. Reading (a) uses the features computed here with IPFX 2.1.2 from the long square sweeps where they agree with the paper's aibs_features_E.csv within 1% for at least half of the cells (39 features, which agree within 1% for 53 to 98% of cells), and the paper's values for the others (custom features the paper did not release, ramp, short square and chirp features, and five adaptation ratios, which agree within 1% for only 4 to 37% of cells). Reading (b) uses the paper's values throughout. The 50% rule is an assumption of this attempt; the claims file's O1 does not say when a recomputed feature counts as computed. Two variants of reading (a) are shown, (a') with the features extracted without the Methods' 500 ms rms noise criterion, and (a, ratios) with the adaptation ratios computed here, for figs3a, fig6d and fig3g; neither changes an outcome except (a') for fig2c-subclass-ephys-differences, whose outcome rests on it.
    • Cell labels (t-type, subclass, layer, region, donor) come from the paper's cell table through the link claim dandiset-cell-link.
  • Not reproducedResults, Morpho-electric diversity in human L1, paragraph 2; Figure 2Cverifier disagreed at firstquestion to the readernames its codes from outside the dataset

    Within the LAMP5 subclass, sag and initial firing rate decrease from the NMBR to the DBP to the LCP2 t-type.

    Within the LAMP5 subclass, sag and initial firing rate decreased from the NMBR t-type to DBP to LCP2 t-types ... Spearman correlation FDR-corrected p<10−3

    Results, Morpho-electric diversity in human L1, paragraph 2; Figure 2C

    What the paper reports

    • Spearman correlation, p < 0.001, FDR-corrected

    Over the 96 LAMP5 cells of the strict set in the dandiset, both features have a positive Spearman rho with the code LCP2 = 0, DBP = 1, NMBR = 2, the direction the criterion asks for; the medians are highest in NMBR, but the initial firing rate is not monotone (DBP 18.6 Hz, LCP2 22.5 Hz). The initial firing rate meets the threshold (rho 0.46, FDR p = 2.6e-5; 3.0e-5 in variant a'; paper's values 2.5e-5). Sag does not (rho 0.28, FDR p = 0.022; 0.015 in a'; paper's values rho 0.36, FDR p = 0.0020; threshold 0.001). With the 14 Amsterdam and Szeged LAMP5 cells the code includes, taken from the paper's feature tables, sag has FDR p = 0.0039, still above 0.001. The test uses filter_dropouts=False, as the code's cell 59 calls run_correlations; with the function's default (True) sag, whose values are all below 1, is left out. The criterion names no partial level and sag fails under every reading, so the claim is not reproduced, by the rule applied to fig4b-adarb2-irregular-firing. The outcome was partially_reproduced through round 2 and was changed to not_reproduced after verification round 3.

    How the test differed from the paper’s method

    • The dandiset lacks the Amsterdam and Szeged LAMP5 cells the code includes; the test runs on the Seattle cells, and the three-site test is a variant using the paper's per-cell features for the other sites.
    • Features follow the claims file's O1. Reading (a) uses the features computed here with IPFX 2.1.2 from the long square sweeps where they agree with the paper's aibs_features_E.csv within 1% for at least half of the cells (39 features, which agree within 1% for 53 to 98% of cells), and the paper's values for the others (custom features the paper did not release, ramp, short square and chirp features, and five adaptation ratios, which agree within 1% for only 4 to 37% of cells). Reading (b) uses the paper's values throughout. The 50% rule is an assumption of this attempt; the claims file's O1 does not say when a recomputed feature counts as computed. Two variants of reading (a) are shown, (a') with the features extracted without the Methods' 500 ms rms noise criterion, and (a, ratios) with the adaptation ratios computed here, for figs3a, fig6d and fig3g; neither changes an outcome except (a') for fig2c-subclass-ephys-differences, whose outcome rests on it.
    • Cell labels (t-type, subclass, layer, region, donor) come from the paper's cell table through the link claim dandiset-cell-link.
  • Not reproducedResults, Rosehip cells, paragraph 1; Figure 4Bverifier disagreed at firstnames its codes from outside the dataset

    Both rosehip t-types have strong sag, but only ADARB2 MC4R fires irregularly, with stronger and faster sag than SST CHRNA4.

    Electrophysiologically, both t-types that comprise the MC4R subclass showed strong sag, but only the ADARB2 MC4R t-type showed the distinctive irregular firing (45) and stronger and faster sag

    Results, Rosehip cells, paragraph 1; Figure 4B

    What the paper reports

    • Dunn's test post hoc to Kruskal-Wallis, p < 0.05, FDR-corrected

    (iii) holds, with median sag SST CHRNA4 0.234 and ADARB2 MC4R 0.374 above LAMP5 0.116 and PAX6 0.051. (iv) holds under both readings of faster, as ADARB2 MC4R has the higher sag and the shorter sag_peak_t (0.045 against 0.052 s) and sag_tau (0.050 against 0.090 s). (i) fails, as ADARB2 MC4R's median irregularity ratio is 0.421 against 0.153 in SST CHRNA4, but Dunn FDR p = 0.18 with 9 SST CHRNA4 cells. (ii) fails, as SST CHRNA4 (0.153) is above LAMP5 (0.114) with Dunn FDR p = 0.046. The criterion names no partial level, and the parts that fail are the claim's point that only ADARB2 MC4R fires irregularly; the direction of the irregularity difference holds, its significance does not. The first run recorded partially_reproduced; changed after verification round 1. Variant (a') gives the same.

    How the test differed from the paper’s method

    • ir_late_mean, sag_peak_t and sag_tau are not computed here and are the paper's values under both readings.
    • Features follow the claims file's O1. Reading (a) uses the features computed here with IPFX 2.1.2 from the long square sweeps where they agree with the paper's aibs_features_E.csv within 1% for at least half of the cells (39 features, which agree within 1% for 53 to 98% of cells), and the paper's values for the others (custom features the paper did not release, ramp, short square and chirp features, and five adaptation ratios, which agree within 1% for only 4 to 37% of cells). Reading (b) uses the paper's values throughout. The 50% rule is an assumption of this attempt; the claims file's O1 does not say when a recomputed feature counts as computed. Two variants of reading (a) are shown, (a') with the features extracted without the Methods' 500 ms rms noise criterion, and (a, ratios) with the adaptation ratios computed here, for figs3a, fig6d and fig3g; neither changes an outcome except (a') for fig2c-subclass-ephys-differences, whose outcome rests on it.
    • Cell labels (t-type, subclass, layer, region, donor) come from the paper's cell table through the link claim dandiset-cell-link.
  • Not reproducedResults, Cross-modality relationships of L1 subclasses and t-types, paragraph 1; Figure 6Averifier disagreed at firstquestion to the readernames its codes from outside the dataset

    Pairwise electrophysiological distinctness (d') of human L1 t-types is smaller within subclasses than between them; the only within-subclass pair with high d' is LAMP5 NMBR against LAMP5 LCP2.

    The resulting t-type similarity matrices (Fig. 6A) showed comparable subclass structure in both electrophysiology and transcriptomics, with smaller d’ values within subclass blocks and higher values outside ... The single within-subclass pair with a high d’ was LAMP5 NMBR and LAMP5 LCP2

    Results, Cross-modality relationships of L1 subclasses and t-types, paragraph 1; Figure 6A

    Nine t-types with at least 5 cells (the legend's rule of at least 4 keeps the same nine), 81 features. Mean within-subclass d' is below the mean between-subclass d' in all nine runs (features computed here 1.24 to 1.31 against 2.48 to 2.54, variant a' 1.28 to 1.30 against 2.52 to 2.56, paper's values 1.12 to 1.23 against 2.39 to 2.49, seeds 0 to 2). The criterion asks that NMBR against LCP2 be the only high within-subclass pair under both of its readings of high. With high as d' >= 2.2 it is so on the features computed here and in (a') for every seed (2.39 for seed 0) and on the paper's values for seed 0 only (no within-subclass pair reaches 2.2 for seeds 1 and 2). With high as above the median between-subclass d' (2.40 to 2.62) no within-subclass pair is high. The subclass structure holds; the single high pair holds only under the first reading. The first run adopted the 2.2 reading as an assumption and recorded reproduced; changed to partially_reproduced after verification round 1, as the criterion asks for both readings. The criterion names no partial level, so the claim is not reproduced; changed to not_reproduced after verification round 3.

    How the test differed from the paper’s method

    • Random forest seeds 0, 1 and 2 are a standard choice; the code sets none.
    • Features follow the claims file's O1. Reading (a) uses the features computed here with IPFX 2.1.2 from the long square sweeps where they agree with the paper's aibs_features_E.csv within 1% for at least half of the cells (39 features, which agree within 1% for 53 to 98% of cells), and the paper's values for the others (custom features the paper did not release, ramp, short square and chirp features, and five adaptation ratios, which agree within 1% for only 4 to 37% of cells). Reading (b) uses the paper's values throughout. The 50% rule is an assumption of this attempt; the claims file's O1 does not say when a recomputed feature counts as computed. Two variants of reading (a) are shown, (a') with the features extracted without the Methods' 500 ms rms noise criterion, and (a, ratios) with the adaptation ratios computed here, for figs3a, fig6d and fig3g; neither changes an outcome except (a') for fig2c-subclass-ephys-differences, whose outcome rests on it.
    • Cell labels (t-type, subclass, layer, region, donor) come from the paper's cell table through the link claim dandiset-cell-link.

Blocked1

  • BlockedResults, Cross-modality relationships of L1 subclasses and t-types, paragraph 2; Figure S8B· Data missing from the datasetquestion to the readernames its codes from outside the dataset

    Trained on the primary dataset with site-dependent features excluded, the classifier reaches 81% accuracy on held-out cells recorded at other sites.

    After excluding features for which the distributions strongly differed from the primary dataset, we found comparable classification performance (81%, Fig. S8B)

    Results, Cross-modality relationships of L1 subclasses and t-types, paragraph 2; Figure S8B

    The 26 held-out cells (17 Szeged, 9 Amsterdam; strict set, core subclasses, soma in L1) are not in the dandiset (it holds only the 210 Seattle cells of P), and the paper names no other deposit of their recordings; the criterion blocks the claim as data_missing in that case. Two DANDI datasets published in 2026 were checked from their metadata. DANDI 000228 (version 0.260829.2040) holds 91 Szeged files from 32 donors, including the donors of 15 of the 17 held-out Szeged cells, but its file paths carry no session id, so they could be linked to cells only by matching features. DANDI 000337 (version 0.260917.2218) holds 21 Amsterdam files; none has the LIMS session id of a held-out Amsterdam cell (5 of the 9 have one in the table), and 8 carry the session id PLACEHOLDER in their paths. Whether the claims file should name 000228 as an input is asked of a reader (questions/000630.yaml).

Human against mouse L1 cells, with dandiset 000020 8

Notebook mouse_comparison.ipynb

Reproduced1

  • ReproducedResults, Cross-species differences in L1, paragraph 4; Figure 3Guses data from outside the dataset

    Human and mouse L1 subclasses have a similar amount of morpho-electric variability but along different features; sag and spike shape adaptation vary in human but little in mouse, while ISI adaptation and AHP vary in mouse.

    we found that the two species had a similar amount of variability (number of significantly different features and their effect size) but varied along different sets of features (Fig. 3G). The most distinct features in human, like sag and spike shape adaptation, showed little variability in mouse, and unlike in human, mouse subclasses varied physiologically in ISI adaptation and spike after-hyperpolarization (AHP) properties

    Results, Cross-species differences in L1, paragraph 4; Figure 3G

    Human 179 cells (92 features), mouse 205 VISp cells (82 features), as the claims file says. Sag and the upstroke adaptation ratio vary across human subclasses (epsilon2 0.57 and 0.46, FDR p < 1e-4) and less in mouse (0.22 and 0.17). In mouse the ISI adaptation features isi_adapt_ratio, adapt_mean and adapt_hero (epsilon2 0.38 to 0.41) and the AHP features fast_trough_deltav_rheo, fast_trough_deltav_hero and trough_slowdeltav_hero (0.31 to 0.40) have FDR p < 1e-4 and larger epsilon2 than in human. Both feature readings agree, and the same holds in variant (a'), with the adaptation ratios computed here (upstroke adaptation ratio epsilon2 0.43 in human against 0.18 in mouse) and with every visual area (VIS, 250 cells), which the first run used. The amount, outside the outcome, is 56 FDR-significant features in human and 73 in mouse VISp (77 in VIS), mean epsilon2 0.17 and 0.22.

    How the test differed from the paper’s method

    • Features follow the claims file's O1. Reading (a) uses the features computed here with IPFX 2.1.2 from the long square sweeps where they agree with the paper's aibs_features_E.csv within 1% for at least half of the cells (38 features computed for both species; 39 for the human cells alone, which agree within 1% for 53 to 98% of cells), and the paper's values for the others (custom features the paper did not release, ramp, short square and chirp features, and five adaptation ratios, which agree within 1% for only 4 to 37% of cells). Reading (b) uses the paper's values throughout. The 50% rule is an assumption of this attempt; the claims file's O1 does not say when a recomputed feature counts as computed. Two variants of reading (a) are shown, (a') with the features extracted without the Methods' 500 ms rms noise criterion, and (a, ratios) with the adaptation ratios computed here, for figs3a, fig6d and fig3g; neither changes an outcome except (a') for fig2c-subclass-ephys-differences, whose outcome rests on it.
    • Mouse cells from DANDI 000020 version 0.210913.1639; 250 of 272 strict mouse L1 cells have a file there, 205 of them in VISp.
    • Cell labels (t-type, subclass, layer, region, donor) come from the paper's cell table through the link claim dandiset-cell-link.

Partially reproduced2

  • Partially reproducedResults, Cross-species differences in L1, paragraph 2; Figure 3D rightuses data from outside the dataset

    Mouse L1 cells have less sag, lower spike amplitude and higher rheobase than human, across subclasses and within at least 2 of the 4 matched subclasses.

    Mouse cells had less sag, lower amplitude spikes, and higher rheobase across types and within at least 2 of 4 matched subclasses

    Results, Cross-species differences in L1, paragraph 2; Figure 3D right

    What the paper reports

    • 2-way ANOVA on ranks, species effect, p < 10⁻³⁸, FDR-corrected

    On the cells the claims file names, human cells of P with soma in L1 (176, the layer filled from the LIMS layer as l1_cross_species.ipynb cell 5 does) and mouse VISp L1 cells (150), 80 features. Directions hold for all three features (mouse sag 0.048 against 0.136, AP height at the ramp 54 against 76 mV, rheobase 140 against 30 pA), with species FDR p < 0.05, and for each feature with an interaction at least 2 of the 4 subclasses differ at p < 0.05 in that direction (LAMP5 and MC4R for all three, L1 VIP for sag and rheobase). AP height has species FDR p 3.4e-33 under O2 reading (a) and 3.3e-34 under (b), and sag 9.5e-36 under (a), so not all three are below 1e-38 under either reading; the readings agree on partially reproduced. The one mouse PAX6 cell in VISp leaves PAX6 out of the ANOVA. The first run used every visual area (VIS, 185 mouse cells), as the code does, where the readings disagree (AP height 2.6e-38 under (a), 1.4e-43 under (b)) and the claim was blocked as methods_underspecified; changed after verification round 1 to the claims file's VISp. With the 22 strict mouse cells missing from DANDI 000020 added from the paper's table (168 VISp cells) the readings disagree as well (sag 2.7e-36 under (a), all three below 1e-38 under (b)), so the missing cells lower the power of the test. With the human layer not filled (164 cells, as the code's other notebooks select) and VISp, AP height has species FDR p 9.3e-32 and 3.7e-33, also above 1e-38 under both readings. Variant (a') gives the same on VISp (AP height 3.4e-33 and 3.3e-34, sag 3.1e-36 under O2 a).

    How the test differed from the paper’s method

    • AP height at the ramp (peak_deltav_ramp) is not computed here and is the paper's value for both species.
    • Features follow the claims file's O1. Reading (a) uses the features computed here with IPFX 2.1.2 from the long square sweeps where they agree with the paper's aibs_features_E.csv within 1% for at least half of the cells (38 features computed for both species; 39 for the human cells alone, which agree within 1% for 53 to 98% of cells), and the paper's values for the others (custom features the paper did not release, ramp, short square and chirp features, and five adaptation ratios, which agree within 1% for only 4 to 37% of cells). Reading (b) uses the paper's values throughout. The 50% rule is an assumption of this attempt; the claims file's O1 does not say when a recomputed feature counts as computed. Two variants of reading (a) are shown, (a') with the features extracted without the Methods' 500 ms rms noise criterion, and (a, ratios) with the adaptation ratios computed here, for figs3a, fig6d and fig3g; neither changes an outcome except (a') for fig2c-subclass-ephys-differences, whose outcome rests on it.
    • Mouse cells from DANDI 000020 version 0.210913.1639 with the paper's mouse labels; 250 of 272 strict mouse L1 cells have a file there.
    • Cell labels (t-type, subclass, layer, region, donor) come from the paper's cell table through the link claim dandiset-cell-link.
    • Mouse VISp cells as the claims file says; the code's mouse set takes every visual area (VIS), shown as a variant.
    • A subclass with fewer than 2 cells of either species with a value is left out of that feature's ANOVA, as the HC3 errors are undefined with one cell; with VISp this leaves out PAX6 (1 mouse cell) for every feature.

Not reproduced2

  • Not reproducedResults, Rosehip cells, paragraph 2; Figure 4Dverifier disagreed at firstuses data from outside the dataset

    The mouse MC4R subclass has moderate sag but no irregular spiking; irregular spiking occurs only in a subset of mouse LAMP5 cells (mainly Lamp5 Ntn1 Npy2r) without other rosehip features.

    the homologous mouse MC4R subclass had moderate sag but no irregular spiking (Fig. 4D). Irregular spiking resembling the human ADARB2 MC4R rosehip t-type was present only in a subset of LAMP5 cells (primarily Lamp5 Ntn1 Npy2r) that did not have other rosehip-like features

    Results, Rosehip cells, paragraph 2; Figure 4D

    235 mouse VIS cells passing QC. MC4R median sag 0.141 to 0.147 is above LAMP5's 0.041 to 0.042 (Dunn FDR p about 1e-9). 4 of 18 MC4R cells have an irregularity ratio above 0.4, so reading (a), none, fails and reading (b), a minority, holds. Of the 30 cells above 0.4, 15 are LAMP5, 11 L1 VIP and 4 MC4R (not mostly LAMP5), and the largest t-type among them is Lamp5 Plch2 Dock5 (8) before Lamp5 Ntn1 Npy2r (6). These two parts fail under both readings, and the criterion names no partial level. With all 272 strict cells from the paper's table, 18 of 34 irregular cells are LAMP5, a majority, but the largest t-type is still Lamp5 Plch2 Dock5 (11), so the outcome is the same; cuts of 0.3 and 0.5 give the same order of t-types or put Vip Col15a1 Pde1a first. Variant (a') gives the same counts. The moderate sag holds. The first run recorded partially_reproduced; changed after verification round 1.

    How the test differed from the paper’s method

    • ir_late_mean is the paper's value (custom code not released).
    • Features follow the claims file's O1. Reading (a) uses the features computed here with IPFX 2.1.2 from the long square sweeps where they agree with the paper's aibs_features_E.csv within 1% for at least half of the cells (38 features computed for both species; 39 for the human cells alone, which agree within 1% for 53 to 98% of cells), and the paper's values for the others (custom features the paper did not release, ramp, short square and chirp features, and five adaptation ratios, which agree within 1% for only 4 to 37% of cells). Reading (b) uses the paper's values throughout. The 50% rule is an assumption of this attempt; the claims file's O1 does not say when a recomputed feature counts as computed. Two variants of reading (a) are shown, (a') with the features extracted without the Methods' 500 ms rms noise criterion, and (a, ratios) with the adaptation ratios computed here, for figs3a, fig6d and fig3g; neither changes an outcome except (a') for fig2c-subclass-ephys-differences, whose outcome rests on it.
    • 22 of the paper's strict mouse L1 cells (20 in VISp layer 1) have no file in DANDI 000020.
    • Cell labels (t-type, subclass, layer, region, donor) come from the paper's cell table through the link claim dandiset-cell-link.
  • Not reproducedResults, Bursting PAX6 TNFAIP8L3 cells, paragraph 2; Figure 5Dverifier disagreed at firstquestion to the readeruses data from outside the dataset

    Mouse PAX6 subclass cells (Lamp5 Krt73) fire doublets at stimulus onset and show a depolarizing hump just below rheobase, marking them as alpha7 cells.

    In mouse L1, the homologous PAX6 subclass was extremely rare, comprising only a few cells in the Lamp5 Krt73 t-type. These cells tended to fire in doublets at stimulus onset ... Mouse doublet-firing cells also showed a depolarizing ‘hump’ for current injection just below rheobase

    Results, Bursting PAX6 TNFAIP8L3 cells, paragraph 2; Figure 5D

    Three Lamp5 Krt73 cells are in DANDI 000020 (the claims file lists 4; the fourth, specimen 710346584 in VISp1, has no file and no value for either feature in the paper's table), two with a value at rheobase + 40 pA. Their depolarizing sag ratios (0.257, 0.273, 0.304) exceed the medians of every other mouse subclass (0.035 to 0.132). Their median initial firing rate, 97.7 Hz (58 and 137 Hz), exceeds LAMP5 (20 Hz) and MC4R (26 Hz) but not L1 VIP (171 to 177 Hz), under both readings and with all 272 strict cells. Variant (a') gives the same medians. The hump holds; the doublet part of the criterion does not, and the criterion names no partial level. The paper says only that these cells tended to fire in doublets at stimulus onset and does not compare them with L1 VIP; whether the criterion's comparison with every other subclass misreads the paper is asked of a reader (questions/000630.yaml). Under the narrower reading, above LAMP5 and MC4R, both parts hold. The first run recorded partially_reproduced; changed after verification round 1.

    How the test differed from the paper’s method

    • sag_depol is the paper's value (custom code not released).
    • Features follow the claims file's O1. Reading (a) uses the features computed here with IPFX 2.1.2 from the long square sweeps where they agree with the paper's aibs_features_E.csv within 1% for at least half of the cells (38 features computed for both species; 39 for the human cells alone, which agree within 1% for 53 to 98% of cells), and the paper's values for the others (custom features the paper did not release, ramp, short square and chirp features, and five adaptation ratios, which agree within 1% for only 4 to 37% of cells). Reading (b) uses the paper's values throughout. The 50% rule is an assumption of this attempt; the claims file's O1 does not say when a recomputed feature counts as computed. Two variants of reading (a) are shown, (a') with the features extracted without the Methods' 500 ms rms noise criterion, and (a, ratios) with the adaptation ratios computed here, for figs3a, fig6d and fig3g; neither changes an outcome except (a') for fig2c-subclass-ephys-differences, whose outcome rests on it.
    • Cell labels (t-type, subclass, layer, region, donor) come from the paper's cell table through the link claim dandiset-cell-link.

Blocked3

  • BlockedResults, Cross-species differences in L1, paragraph 2; Figure 3E· Data missing from the datasetuses data from outside the dataset

    The human versus mouse electrophysiological differences found against VISp are replicated against mouse TEa, so they are not regional.

    We replicated these findings in a comparison between MTG and a smaller TEa dataset, verifying that cross species differences were not due to regional differences between MTG and VISp

    Results, Cross-species differences in L1, paragraph 2; Figure 3E

    What the paper reports

    • Mann-Whitney test, p < 0.05, FDR-corrected

    The mouse TEa comparison needs the Amsterdam TEa recordings (the code reads mansvelder_tea_2022_09_16.csv from a local project folder, not in its repository) and the Allen TEa cells. The paper names no deposit for either; the 15 TEa cells of the paper's mouse table all have a LIMS id, but none has a file in DANDI 000020 version 0.210913.1639, and the code's repository holds no TEa features.

  • BlockedResults, Cross-species differences in L1, paragraph 3; Figure 3F· Data missing from the datasetuses data from outside the dataset

    In nucleated patches, mouse L1 neurons (only LAMP5 cells were sampled in mouse) have much higher A-type K+ conductance than human, with comparable D-type conductance.

    Compared with human neurons, mouse neurons showed much higher A-type K+ conductance but comparable slow inactivating (D-type) conductance

    Results, Cross-species differences in L1, paragraph 3; Figure 3F

    Nucleated-patch voltage clamp sweeps (stimulus codes starting with Nuc) are in 38 of the 210 human files and in 25 of the 250 strict mouse L1 files of DANDI 000020 (15 of them LAMP5 cells), so IKA and IKD could be computed for both species. The conductance densities the claim compares need each patch's surface area, measured from images that are not public, so the claim stays blocked as data_missing. The conductances themselves were not computed here.

  • BlockedFigure 1E legend; Results, L1 patch-seq pipeline and transcriptomic references, paragraph 3· Metadata insufficientdata in per-cell t-type tables in Zenodo doi:10.5281/zenodo.8310226 (human and mouse l1_dataset_2023_02_06.csv), from the NeMO transcriptomes

    Subclass proportions in the L1 patch-seq data differ between human and mouse for every subclass except L1 VIP, PAX6 being the notable difference.

    All cross-species proportion differences (except L1 VIP) significant at FDR-corrected p<0.001, one vs. rest Fisher’s exact tests

    Figure 1E legend; Results, L1 patch-seq pipeline and transcriptomic references, paragraph 3

    What the paper reports

    • one vs. rest Fisher's exact tests, p < 0.001, FDR-corrected

    The test counts, for each species, cells with soma in L1 by category, including the cells of deeper t-types. The human side is in the public cell table (253 cells with soma in L1, 22 of deeper t-types). The mouse side is the code's full mouse patch-seq metadata (shiny_mouse, read from Allen Institute servers); the public mouse table (547 rows) holds only cells of the 8 mouse L1 t-types, none of a deeper t-type, so the mouse denominators and the deeper t-type category cannot be formed. Not run.

Morphology claims from the paper's deposited feature table 4

Notebook morphology_tables.ipynb

Partially reproduced3

  • Partially reproducedResults, Morpho-electric diversity in human L1, paragraph 1; Figure 2Ddata in Brain Image Library doi:10.35077/g.606 (reconstructions); morphology features in Zenodo doi:10.5281/zenodo.8310226 (data/RawFeatureWide_human+derivatives.csv)

    Human L1 subclasses differ morphologically in vertical orientation of axons and dendrites, axon extent and shape, and dendrite branching (Kruskal-Wallis, FDR p < 1e-3).

    Morphologically, subclasses were distinguished by vertical orientation of axons and dendrites, axon extent and shape, and dendrite branching

    Results, Morpho-electric diversity in human L1, paragraph 1; Figure 2D

    What the paper reports

    • Kruskal-Wallis test, p < 0.001, FDR-corrected

    64 reconstructed cells of the four core subclasses, 51 features from the paper's deposited morphology table; 4 features have FDR p < 1e-3. Of the three features Fig. 2D plots, the fraction of dendrite below the soma (FDR p = 2.0e-4) and the axon horizontal extent (4.1e-4) are below 1e-3, the number of dendrite branches (0.0034) is not. The axon vertical orientation features have FDR p 0.008 to 0.09.

    How the test differed from the paper’s method

    • Tested on the paper's per-cell morphology features as deposited in its code archive, not recomputed from the reconstructions in the Brain Image Library.
    • The claims file gives no criterion; the claim was judged on the three features of Fig. 2D (l1_subclass_distinctness.ipynb cell 21) having FDR p < 1e-3.
  • Partially reproducedResults, Rosehip cells, paragraph 1; Figure 4Bdata in Brain Image Library doi:10.35077/g.606; features in Zenodo doi:10.5281/zenodo.8310226

    MC4R cells are quantitatively distinct from other L1 types in maximum axonal path distance and axon branch frequency.

    were quantitatively distinct from other L1 types in terms of maximum axonal path distance and branch frequency

    Results, Rosehip cells, paragraph 1; Figure 4B

    What the paper reports

    • Mann-Whitney test against rest of L1, p < 10⁻⁴, FDR-corrected

    12 MC4R cells against 66. Axon branch frequency 3.01 against 1.36 per 100 um (FDR p = 1.2e-6, below 1e-4). Maximum axonal path 662 against 992 um (FDR p = 0.0029, not below 1e-4).

    How the test differed from the paper’s method

    • Tested on the paper's deposited morphology features.
    • Judged on FDR p < 1e-4 for both features, the threshold of the Fig. 4B legend.
  • Partially reproducedResults, Bursting PAX6 TNFAIP8L3 cells, paragraph 1; Figure 5Bdata in Brain Image Library doi:10.35077/g.606; features in Zenodo doi:10.5281/zenodo.8310226

    PAX6 TNFAIP8L3 cells have more dendritic branches and a horizontal dendritic extent over 550 um wide.

    as did the number of dendritic branches and large horizontal dendritic extent, over 550 microns wide

    Results, Bursting PAX6 TNFAIP8L3 cells, paragraph 1; Figure 5B

    What the paper reports

    • Mann-Whitney test against rest of L1, p < 0.05, FDR-corrected

    Two PAX6 TNFAIP8L3 cells against 76. Horizontal dendritic extent 583 and 819 um, both over 550 um, against a median of 140 um (FDR p = 0.017). Dendrite branches 50 and 68 against a median of 32 (FDR p = 0.085, not below 0.05).

    How the test differed from the paper’s method

    • Tested on the paper's deposited morphology features.
    • Judged on FDR p < 0.05 (Fig. 5B legend) with TNFAIP8L3 higher for both features, and each cell's extent over 550 um.

Blocked1

  • BlockedResults, Morpho-electric diversity in human L1, paragraph 3; Figure S6A· Metadata insufficientdata in Brain Image Library doi:10.35077/g.606; morphology features in Zenodo doi:10.5281/zenodo.8310226

    Cells from tumor patients have higher dendritic branching than cells from epilepsy patients, not explained by brain area or subclass.

    with the exception of higher dendritic branching in cells from tumor patients compared to epilepsy patients

    Results, Morpho-electric diversity in human L1, paragraph 3; Figure S6A

    What the paper reports

    • Mann-Whitney test, p < 0.05, FDR-corrected

    The public cell table gives a medical condition for 20 of the 71 reconstructed strict-set cells with an L1 t-type (13 epileptic, 7 not; 51 have none); the code read the conditions of all donors from the Allen Institute's donor database. On these 20 cells the dendrite branch count is higher in non-epileptic donors (median 37 against 26) with FDR p = 0.94, and the check within MTG LAMP5 cells cannot be run, as only epileptic donors are labelled there.

Not tested in a notebook 14

13 other, 1 metadata insufficient

Blocked14

  • BlockedResults, Cross-modality relationships of L1 subclasses and t-types, paragraph 1; Figure 6B· Otheruses data from outside the dataset

    Electrophysiological and transcriptomic d' of human L1 t-type pairs are correlated (Pearson r = 0.59, p = 0.00016).

    d’ metrics were highly correlated between modalities, demonstrating that cell types with distinctive transcriptomes have similarly distinctive electrophysiological properties (Pearson r=0.59, p=0.00016

    Results, Cross-modality relationships of L1 subclasses and t-types, paragraph 1; Figure 6B

    What the paper reports

    • Pearson correlation, r = 0.59, p = 1.6 × 10⁻⁴

    Not attempted in this run; its inputs are public. It needs the patch-seq transcriptomes (ps_human.RData in the paper's code archive) and a refit of the zero-inflated negative binomial discriminant, whose fitted curves (zinb_human.h5) are not public and are refitted as the criterion says; the run gave its time to the claims on the dandiset.

  • BlockedResults, Cross-species differences in L1, paragraph 1; Figure 3B and S6D· Metadata insufficientdata in Zenodo doi:10.5281/zenodo.8310226 (data/Source data cortical structure L1.csv and Source data cortical structure L1 all areas.csv)

    Human L1 is thicker than mouse L1 but not less dense, with smaller cell bodies.

    human L1 was thicker but not less dense, with smaller cell bodies compared with several mouse neocortical areas

    Results, Cross-species differences in L1, paragraph 1; Figure 3B and S6D

    What the paper reports

    • Kruskal-Wallis test, Dunn's post hoc (MTG against TEa), p < 0.05 (n = human MTG 76 ROIs (3016 cells, 16 cases); mouse TEa 29 ROIs (400 cells, 3 animals))

    The code (l1_depth_revisions.ipynb cells 8 to 12) rescales the mouse thickness, soma area, density and count values of the deposited source data by each slide's scanner resolution, read from the Allen Institute's LIMS database, which is not public; the deposited CSV does not carry the resolutions. Not run.

  • BlockedResults, L1 patch-seq pipeline and transcriptomic references, paragraph 1; Figure 1A· Otherdata in Allen Brain Map RNA-seq portal (human MTG snRNA-seq of Hodge et al. 2019, mouse VISp scRNA-seq of Tasic et al. 2018), as the Methods cite them

    In transcriptomic reference data, many human L1 t-types form separated clusters while mouse L1 t-types vary more continuously, suggesting stronger transcriptomic specialization in human L1.

    many human t-types formed separated clusters, with others clustered in groups of related t-types, whereas mouse L1 t-types showed more continuous variability

    Results, L1 patch-seq pipeline and transcriptomic references, paragraph 1; Figure 1A

    Not attempted in this run, not for lack of data; the run gave its time to the claims on the dandiset. It needs the Allen Brain Map human MTG snRNA-seq and mouse VISp scRNA-seq references and the NB discriminant d'.

  • BlockedResults, L1 patch-seq pipeline and transcriptomic references, paragraph 1; Figure 1B; Methods, Subclasses and cross-species homology· Otherdata in Allen Brain Map RNA-seq portal (human MTG snRNA-seq, mouse VISp scRNA-seq)

    Ten human and eight mouse L1 t-types are defined from the references; grouping human t-types with d' below 2.2 forms three subclasses, leaving three t-types ungrouped.

    we identified 10 L1 t-types in human and 8 in mouse ... This formed three subclasses, with three t-types remaining ungrouped

    Results, L1 patch-seq pipeline and transcriptomic references, paragraph 1; Figure 1B; Methods, Subclasses and cross-species homology

    Not attempted in this run, not for lack of data; the run gave its time to the claims on the dandiset. It needs the Allen Brain Map references and the NB discriminant d' grouping.

  • BlockedResults, L1 patch-seq pipeline and transcriptomic references, paragraph 3; Figure 1D· Otherdata in Allen Brain Map RNA-seq portal references and the integrated coordinates in Zenodo doi:10.5281/zenodo.8310226 (data/scalign_coords.rda)

    Cross-species matching of mouse t-types to human subclasses gives four homology-driven subclasses; two human L1 t-types (SST BAGE2, VIP PCDH20) are homologous to deeper-layer mouse types and are left out.

    These matches resulted in four homology-driven subclasses (called subclasses hereafter) with proportions largely comparable across species ... Two additional human L1 t-types (SST BAGE2 and VIP PCDH20) were excluded from cross-species L1 subclasses because of their homology to t-types found in deeper layers, but not L1 of mouse neocortex

    Results, L1 patch-seq pipeline and transcriptomic references, paragraph 3; Figure 1D

    Not attempted in this run, not for lack of data; the run gave its time to the claims on the dandiset. It needs the references and the integrated coordinates of the cross-species alignment.

  • BlockedResults, L1 patch-seq pipeline and transcriptomic references, paragraph 6; Figure S2A· Otherdata in Zenodo doi:10.5281/zenodo.8310226 (data/merfish_counts.csv, merfish_proportions.csv and the per-cell tables) and the Allen Brain Map human MTG snRNA-seq reference

    Compared with snRNA-seq, patch-seq sampled fewer SST BAGE2 and more PAX6 CDH12 and VIP TSPAN12 cells; MERFISH proportions did not differ from patch-seq.

    patch-seq had fewer SST BAGE2 cells and more PAX6 CDH12 and VIP TSPAN12 compared to snRNA-seq (p<0.05, False discovery rate or FDR-corrected Fisher’s exact test). MERFISH had intermediate proportions of SST BAGE2 with no significant differences compared to patch-seq (p>0.18)

    Results, L1 patch-seq pipeline and transcriptomic references, paragraph 6; Figure S2A

    What the paper reports

    • patch-seq against snRNA-seq: Fisher's exact test, p < 0.05, FDR-corrected
    • MERFISH against patch-seq: Fisher's exact test, p > 0.18

    Not attempted in this run, not for lack of data; the run gave its time to the claims on the dandiset. It needs the human MTG snRNA-seq reference counts and the MERFISH tables.

  • BlockedFigure S1D legend; Results, L1 patch-seq pipeline and transcriptomic references, paragraph 5· Otherdata in Zenodo doi:10.5281/zenodo.8310226 (data/ps_human.RData) and the Allen Brain Map human MTG snRNA-seq reference

    Marker gene expression by t-type correlates strongly between patch-seq and the snRNA-seq reference (r = 0.84).

    Correlation of marker gene expression between patch-seq and snRNA-seq reference (r=0.84, p<10-18)

    Figure S1D legend; Results, L1 patch-seq pipeline and transcriptomic references, paragraph 5

    What the paper reports

    • correlation, r = 0.84, p < 10⁻¹⁸

    Not attempted in this run, not for lack of data; the run gave its time to the claims on the dandiset. It needs the patch-seq transcriptomes and the snRNA-seq reference.

  • BlockedResults, Cross-species differences in L1, paragraph 1; Figure 3D left· Otherdata in Brain Image Library doi:10.35077/g.606 and the mouse reconstructions the paper lists (download.brainimagelibrary.org/biccn/zeng/pseq/morph/200526/); features in Zenodo doi:10.5281/zenodo.8310226

    Human L1 neurites are more tortuous (smaller contraction ratio) than mouse, mouse dendrites are more branched, and mouse axons rarely extend above the dendrites.

    Unlike human axons, mouse axons rarely extended above dendrites (Fig. 3D left), perhaps reflecting sublaminar structure found only in the thicker human L1. Human neurites were also structured differently, with smaller contraction ratios (higher tortuosity) compared to the straighter but more heavily branched mouse dendrites

    Results, Cross-species differences in L1, paragraph 1; Figure 3D left

    What the paper reports

    • 2-way ANOVA on ranks, species effect, p < 10⁻⁷, FDR-corrected

    Not attempted in this run; its inputs are public (the mouse morphology features are in the code's archive, RawFeatureWide_mouse+derivatives.csv). It needs the mouse morphology table and the code's L1 and L2 border selection; the run gave its time to the claims on the dandiset.

  • BlockedResults, Cross-species differences in L1, paragraph 1; Figure S3C· Otherdata in Brain Image Library doi:10.35077/g.606; features in Zenodo doi:10.5281/zenodo.8310226

    Human L1 neurons are slightly larger than mouse in horizontal extent, with no species difference in vertical dimensions or dendritic diameter.

    Although human neurons across subclasses were slightly larger in horizontal extent, no differences were observed in vertical dimensions or dendritic diameter (Fig. S3C)

    Results, Cross-species differences in L1, paragraph 1; Figure S3C

    Not attempted in this run; its inputs are public (the mouse morphology features are in the code's archive, RawFeatureWide_mouse+derivatives.csv). It needs the mouse morphology table and the code's L1 and L2 border selection; the run gave its time to the claims on the dandiset.

  • BlockedResults, Cross-species differences in L1, paragraph 3; Figure S3G· Otherdata in Brain Image Library doi:10.35077/g.606 (reconstructions) and the Allen Cell Types model for specimen 475585413 (celltypes.brain-map.org)

    Passive models built on reconstructed morphologies explain input resistance variability in human (R2 = 0.35) but not mouse (R2 = 0.03) LAMP5 cells.

    Simulations of passive biophysical models based on reconstructed morphologies showed that input resistance variability in human but not mouse L1 cells can be explained by morphology

    Results, Cross-species differences in L1, paragraph 3; Figure S3G

    What the paper reports

    • human: linear regression, R2 = 0.35, p = 4 × 10⁻⁶
    • mouse: linear regression, R2 = 0.03, p = 0.46

    Not attempted in this run, not for lack of data; the run gave its time to the claims on the dandiset. It needs the reconstructions and passive model simulations.

  • BlockedResults, Cross-species differences in L1, paragraph 3; Figure S3E· Otherdata in Zenodo doi:10.5281/zenodo.8310226 (data/ps_human.RData, ps_mouse.RData) and NeMO

    Genes for A-type K+ channels (KCND2, KCND3, KCNH7) are more highly expressed in mouse than human L1 neurons and correlate with action potential features.

    the expression of genes (KCND2, KCND3, and KCNH7) associated with fast inactivating, A-type K+ channels ... was higher in mouse neurons and was correlated with several action potential features

    Results, Cross-species differences in L1, paragraph 3; Figure S3E

    Not attempted in this run, not for lack of data; the run gave its time to the claims on the dandiset. It needs the human and mouse patch-seq transcriptomes.

  • BlockedResults, Rosehip cells, paragraph 1; Figure 4C· Otherdata in Allen Brain Map human MTG snRNA-seq reference

    HTR1F marks the rosehip subclass, and GRM5 and RELN are lower in ADARB2 MC4R than in SST CHRNA4 neurons.

    found markers distinguishing the entire rosehip subclass from the rest of L1, including HTR1F (5HT receptor 1F), along with markers distinguishing the rosehip subtypes ... GRM5 (metabotropic glutamate receptor 5) and RELN (Reelin) showed lower expression in ADARB2 MC4R neurons

    Results, Rosehip cells, paragraph 1; Figure 4C

    Not attempted in this run, not for lack of data; the run gave its time to the claims on the dandiset. It needs the human MTG snRNA-seq reference.

  • BlockedResults, Bursting PAX6 TNFAIP8L3 cells, paragraph 3; Figure 5C· Otherdata in Allen Brain Map human MTG snRNA-seq reference

    Both human PAX6 t-types match the alpha7 marker signature and strongly express the T-type calcium channel gene CACNA1G.

    and strongly expressed the T-type calcium channel alpha subunit gene CACNA1G

    Results, Bursting PAX6 TNFAIP8L3 cells, paragraph 3; Figure 5C

    Not attempted in this run, not for lack of data; the run gave its time to the claims on the dandiset. It needs the human MTG snRNA-seq reference.

  • BlockedResults, Cross-modality relationships of L1 subclasses and t-types, paragraph 1; Figure 6C· Otherdata in Zenodo doi:10.5281/zenodo.8310226 (data/ps_human.RData, ps_mouse.RData), DANDI 000020 and Brain Image Library doi:10.35077/g.606

    Subclasses are more transcriptomically distinct in human than mouse, and in mouse the VIP subclass is highly distinct in all modalities while the others are less so.

    These results confirmed the generally higher transcriptomic distinctness of subclasses in human and show that in mouse the VIP subclass was highly distinct in all modalities, with other subclasses generally less distinct

    Results, Cross-modality relationships of L1 subclasses and t-types, paragraph 1; Figure 6C

    Not attempted in this run, not for lack of data; the run gave its time to the claims on the dandiset. It needs transcriptomes, mouse electrophysiology and morphology d' across modalities.

Findings about the data

What attempts found about the dataset itself, for its owner and the archive.

  • Description missingThe files carry no t-type, subclass, cortical layer, brain region or donor medical condition, and no specimen id of the paper's cell table. They can be linked to the paper's table only through the LIMS number in session_id, which equals the Ephys_Roi_Result number inside the table's internal nwb_path column; the dandiset's description points to the code repository but does not say how to link.
  • Identifier missingSix files (five of donor 1122692698, one of 1154304730) carry a time stamp such as 2021_08_17_112853 in general/source_script file_name, where the other 204 carry the cell name (for example H21.03.315.11.11.01.01).
  • File format errorIn 145 of 210 files, 2586 long square sweeps that stopped early hold zeros for the samples that were not acquired, where NWB readers such as IPFX expect missing values. IPFX's integrity check passes them and reads the step to 0 mV as a spike, which changes rheobase and spike features unless the sweeps are left out.
  • File format errorbias_current is stored in pA, with a unit attribute of pA, where the NWB schema fixes the unit of bias_current as amperes; a reader that follows the schema gets values 10^12 times too large.
  • Metadata errorThe two files of donor 922967568 state an age of P0.0D where the paper's table gives the age as unknown, and one file (session 977186103, cell H19.03.321.12.04.01.04) states sex unknown where the table gives M. Ages are stated as whole years times 365 days. The species is written as Homo Sapiens in 192 files and Homo sapiens in 18.
  • Data missingThe dandiset holds only the 210 Seattle cells of the paper's primary set. The 50 Amsterdam (22) and Szeged (28) cells of the strict L1 set, which the paper uses as held-out validation (Fig. S8B) and in its LAMP5 t-type analysis, are not in it, and the paper names no other deposit of them.
  • Selection not documentedThe dandiset holds exactly the paper's primary set P, the Seattle cells of the strict L1 set (soma in L1 or within 40 um of the L1/L2 border) whose long square features were extracted. The 12 Seattle cells of the strict set that failed feature extraction and the other Seattle cells of the paper's table are not deposited, and the dandiset's description does not say how the cells were selected.
  • Description missingThe donor medical condition is given in the public cell table for only 86 of the 194 cells of P in L1 t-types and 20 of the 71 reconstructed strict-set cells with an L1 t-type; the paper's code read it from the Allen Institute's donor database. The claims on medical condition cannot be repeated on the paper's cells.
  • Methods not availableSeveral features the claims rest on (irregularity ratio, depolarizing sag, ADP slope and voltage, sag time to peak and time constant, the ramp, short square and chirp features) come from code the Methods say will be released in a future IPFX version; it is not in IPFX 2.1.2 nor in the code repository. The adaptation ratios computed here from the Methods' definition (third over first spike on the lowest step with at least 4 spikes) agree with the paper's values within 1% for only 4 to 53% of cells (six ratios; 4 to 37% for the five not used). The authors are asked whether the feature code can be released.
  • Methods not availableThe authors are asked what d' counts as high in Fig. 6A, where LAMP5 NMBR against LCP2 is said to be the only within-subclass pair with high d'. With the 2.2 grouping threshold it holds here on the features computed here for three seeds and on the paper's values for one of three; with the median between-subclass d' (2.40 to 2.62) no within-subclass pair is high.
  • Methods not availableThe authors are asked whether the two-way ANOVA of Fig. 3D was run on ranks with Type II sums of squares and heteroskedasticity-corrected tests (legend and Data S4), or on raw values with Type I sums of squares, as the code calls anova_lm without its robust option. With every visual area, as the code takes the mouse cells, the AP height species effect is FDR p = 2.6e-38 under the first and 1.4e-43 under the second, on either side of the legend's 1e-38.
  • Methods not availableThe authors are asked how the sweep QC criterion of rms noise below 0.5 mV over 500 ms (Methods, Quality control) was measured. Measured with IPFX on the deposited files, it leaves out sweeps from which the paper's per-cell values were computed: in 7 of the 9 cells where IPFX falls back to a lower sweep at rheobase + 40 pA and the value disagrees with the paper's, the paper's value comes from a sweep that fails only this criterion here. Without it, 38 of the 39 recomputed features agree with the paper's values for more cells, and the initial firing rate difference across subclasses (Fig. 2C) has FDR p 3.9e-9 against 4.7e-7 with it.
  • Published code disagreesThe Fig. S3A legend gives R2 = 0.74 for the upstroke adaptation ratio against sag. The code's regression (run_regressions, OLS with HC3) on the paper's own per-cell values over the cells of P in L1 t-types gives R2 = 0.36 (192 cells), and 0.31 on t-type medians.
  • OtherFor the mouse comparison (DANDI 000020 version 0.210913.1639, an outside input), 22 of the paper's 272 strict mouse L1 cells, 20 of them in VISp layer 1 and one of them a Lamp5 Krt73 cell, have no file in that version, and none of the paper's 15 mouse TEa cells does.
  • Published code disagreesThe paper compares human L1 with mouse VISp L1 (Fig. 3E legend; Methods), while the code's cross-species notebook (l1_cross_species.ipynb cell 5) takes mouse cells from every visual area (VISp, VISpm, VISl and others; 185 cells against 150 in VISp here). With VISp alone the AP height species effect is FDR p 3.3e-34 to 3.4e-33, above the legend's 1e-38.
  • OtherNucleated-patch voltage clamp sweeps are in 38 human files of the dandiset and 25 strict mouse L1 files of DANDI 000020, but the patch surface areas the paper's conductance densities (Fig. 3F) need, measured from images, are not deposited.

Questions

Where the author or a verifier believed the claims file misread the paper, they asked, citing the paper, and a reader who had not seen the data answered from the paper alone, amending the claims file where it was wrong. The author then ran the claim as answered. Attempts before protocol pilot-11 also asked here for method details the claims file did not give.

  • answered 2026-10-31asked 2026-10-31about fig2b-subclass-ephys-profiles

    Part (iii) of the criterion requires PAX6 to have the highest median initial firing rate (first_isi_inv_hero) of the four subclasses. The paper says PAX6 cells have a "high initial firing rate" and does not compare them with L1 VIP cells on this feature. Should (iii) be read as PAX6 above LAMP5 and MC4R, the subclasses the paragraph contrasts it with, in place of the highest of all four?

    Passage. PAX6 cells had similar axons to LAMP5 cells, occasionally with descending branches, and sparse downward dendrites, along with minimal sag and high initial firing rate at the onset of response to depolarizing current injection (Fig. 2A-B). (Results, Morpho-electric diversity in human L1, paragraph 2)

    Why it matters. The median initial firing rate is 49.3 Hz in PAX6 and 54.6 Hz in L1 VIP (Dunn FDR p 0.39 to 1 between them), so (iii) fails and the claim is not reproduced. PAX6 is above LAMP5 (about 32 Hz) and MC4R (about 29 to 31 Hz) with Dunn FDR p of 3.4e-5 or less, so under the narrower reading parts (i) to (iii) all hold and the claim would be reproduced.

    The reader’s answer. Changed. The paper says PAX6 cells have "minimal sag and high initial firing rate at the onset of response to depolarizing current injection (Fig. 2A-B)" right after describing LAMP5 cells, and it nowhere ranks PAX6 above L1 VIP on this feature, so "highest of the four" read more into the text than it states. Part (iii) of the criterion now requires the PAX6 median first_isi_inv_hero to exceed those of LAMP5 and of MC4R, which keeps "high" as above most other subclasses without a comparison with L1 VIP that the paper does not make.
  • openasked 2026-10-31about figs3a-sag-adaptation

    The criterion requires that "cells with more sag show less change of spike upstroke from the first to the third spike". The paper says only that spike adaptation properties show a "strong inverse relationship" with sag. With the upstroke adaptation ratio as third spike over first, the order that matches the paper's per-cell table, all ratios are below 1 and the slope on sag is negative, so cells with more sag have a larger fall of upstroke, which is more change. Should the direction part of the criterion be read as a negative slope of the ratio on sag (the inverse relationship the paper states), in place of less change with more sag?

    Passage. Spike adaptation properties showed a strong inverse relationship with sag across the dataset (Fig. S3A). (Results, Morpho-electric diversity in human L1, paragraph 1); Trendline from linear regression (right) with shading showing bootstrapped 95% CI (R2=0.74, p<10-13). (Fig. S3 legend, panel A)

    Why it matters. The slope is -0.61 on the features computed here and -0.64 on the paper's values, so the direction holds under the paper's words and fails under the criterion's. It cannot change the outcome of this attempt, which fails on R2 (0.33 and 0.36 against 0.74 +/- 0.074), but a later attempt that matched R2 would be judged on the direction.

    No reader has answered it yet.
  • openasked 2026-10-31about figs8b-classifier-holdout

    The criterion blocks the claim as data_missing when the dandiset does not hold the held-out Amsterdam and Szeged cells. DANDI 000228 (version 0.260829.2040, contributors include Chartrand, Tamas and Molnar) holds 91 Szeged files from the donors of 15 of the 17 held-out Szeged cells, and DANDI 000337 (version 0.260917.2218, Mansvelder lab) holds 21 Amsterdam files. Neither is cited by the paper. Should the claims file name them as outside inputs for this claim, with a link claim that matches their files to the held-out cells?

    Passage. After excluding features for which the distributions strongly differed from the primary dataset, we found comparable classification performance (81%, Fig. S8B) (Results, Cross-modality relationships of L1 subclasses and t-types, paragraph 2)

    Why it matters. The 000228 file paths carry no session id (subjects are named by donor), so a link would have to match their features to the paper's tamas_features_E.csv within each donor; none of the 9 held-out Amsterdam cells has its LIMS session id among the 000337 files. If the files can be linked, the Szeged half of the held-out test could be run, and the claim would no longer be blocked as data_missing.

    No reader has answered it yet.
  • openasked 2026-10-31about fig5d-mouse-pax6-doublets

    The criterion requires the median first_isi_inv_hero of the mouse Lamp5 Krt73 cells to exceed that of every other mouse subclass, L1 VIP included. The paper says only that these cells "tended to fire in doublets at stimulus onset" and does not compare their initial firing rate with L1 VIP cells. Should the doublet part be read as Lamp5 Krt73 above LAMP5 and MC4R, the comparison a reader adopted for part (iii) of fig2b-subclass-ephys-profiles, in place of above every other subclass?

    Passage. In mouse L1, the homologous PAX6 subclass was extremely rare, comprising only a few cells in the Lamp5 Krt73 t-type. These cells tended to fire in doublets at stimulus onset ... sometimes followed by a delayed ADP (Fig. 5C). (Results, Bursting PAX6 TNFAIP8L3 cells, paragraph 2)

    Why it matters. The Lamp5 Krt73 median initial firing rate is 97.7 Hz (two cells with a value), above LAMP5 (20 Hz) and MC4R (26 Hz) but below L1 VIP (171 to 177 Hz), so the claim fails only on the comparison with L1 VIP and is not reproduced. The depolarizing sag ratio part holds. Under the narrower reading both parts hold and the claim would be reproduced.

    No reader has answered it yet.
  • openasked 2026-10-31about fig2c-lamp5-gradient

    The criterion requires sag and first_isi_inv_hero each to have FDR p < 0.001 in the code's run_correlations test (cell 59, filter_dropouts=False, Benjamini-Hochberg across features). On the paper's own per-cell values this test gives sag FDR p = 0.0020 over the 96 Seattle LAMP5 cells and 0.0039 with the 14 Amsterdam and Szeged cells added. Does the criterion prescribe the test that produced the paper's "p<10−3" (for example the cell set, the features corrected over, or the dropout filter), or should sag be read under a different test?

    Passage. Within the LAMP5 subclass, sag and initial firing rate decreased from the NMBR t-type to DBP to LCP2 t-types (Fig. 2C: strip plots within boxplot; Spearman correlation FDR-corrected p<10−3). (Results, Morpho-electric diversity in human L1, paragraph 2)

    Why it matters. Raised by the round-3 verifier. Sag fails the threshold under every reading, including the paper's own values, so either the criterion's method differs from what produced the paper's statement or the statement does not hold for sag. The claim is not reproduced on the criterion as written.

    No reader has answered it yet.
  • openasked 2026-10-31about fig6a-ephys-dprime-subclass-structure

    The criterion tests "the only within-subclass pair with high d' is LAMP5 NMBR against LAMP5 LCP2" on the electrophysiological d' matrix alone. In the paper the sentence follows the cross-modality comparison (Fig. 6B). Should it be read as referring to the transcriptomic matrix, or to both matrices, in place of the electrophysiological one alone?

    Passage. Of note, d’ metrics were highly correlated between modalities ... (Pearson r=0.59, p=0.00016; Fig. 6B). The single within-subclass pair with a high d’ was LAMP5 NMBR and LAMP5 LCP2, which sit at opposite ends of the LAMP5 continuum. (Results, Cross-modality relationships of L1 subclasses and t-types, paragraph 1)

    Why it matters. Raised by the round-3 verifier. On the electrophysiological matrix the claim fails under the criterion's second reading of high (above the median between-subclass d', 2.40 to 2.62), where no within-subclass pair is high, NMBR against LCP2 included (2.39). If the sentence is about the transcriptomic matrix, this part of the claim would need the transcriptomic d', which the dandiset does not hold.

    No reader has answered it yet.

Notebooks

Every registered entry that uses this dataset. An entry can hold several notebooks, and can use more than one dataset.

Reproduction Human layer 1 interneuron electrophysiology (Chartrand et al. 2023)

Tests the electrophysiology findings of Chartrand et al. (2023) on dandiset 000630, which holds the current clamp recordings of the paper's 210 Seattle human L1 patch-seq cells. Features are extracted with IPFX from the long square sweeps and compared with the paper's per-cell table; cell types come from the paper's cell table, linked by the LIMS identifier. A second notebook compares the human cells with the paper's mouse L1 cells from dandiset 000020. A third notebook tests four morphology claims on the paper's deposited morphology features. Also uses DANDI:000020. All files

Verification

  • Round 1
    2026-10-31
    Agreed with 36 of 41 outcomes. Independent agent run by CatalystNeuro (same harness, separate context, did not write the notebooks). Reviewed: Round 1. The three executed notebooks with the conclusion cells and the summaries removed, the helper module and the claims file, with the paper. The verifier ran the helper statistics on synthetic data and queried the archive; it gave its own outcome for each claim. It disagreed with five outcomes (dandiset-cell-link, fig4b-adarb2-irregular-firing, fig6a-ephys-dprime-subclass-structure, fig4d-mouse-no-rosehip-ephys and fig5d-mouse-pax6-doublets) and corrected several reasons for blocks. Report in transcripts/000630/verifier-1-report.md.
    • dandiset-cell-link: the verifier’s outcome was “Partially reproduced”. R c14: all 210 files match 210 distinct rows. Sex agrees for 209/210 (one file says unknown). Age agrees for 207/208, with one off by 1 year under the notebook's own floor(x+0.05) rounding. 39 of 44 computed features agree within 1% for at least half the cells. The criterion asks every record to agree, so this is partial (>=90%). Also (B11) the age match uses an ad hoc rounding, and (B2) the cells where first_isi_inv_hero disagrees are never inspected.
    • fig4b-adarb2-irregular-firing: the verifier’s outcome was “Not reproduced”. R c38: (i) fails, because ADARB2 against CHRNA4 on ir_late_mean has Dunn FDR 0.18. (ii) fails, because CHRNA4 is above LAMP5 with FDR 0.046. (iii) and (iv) hold under both readings of faster.
    • fig6a-ephys-dprime-subclass-structure: the verifier’s outcome was “Partially reproduced”. R c42: mean within-subclass d' is below between-subclass d' in all 6 runs. NMBR/LCP2 is the only high within-subclass pair under >=2.2 in 4 of 6 runs (only seed 0 under (b)). Under above median between no within pair is high, so the criterion's both readings condition fails.
    • fig4d-mouse-no-rosehip-ephys: the verifier’s outcome was “Not reproduced”. M c12: MC4R sag is above LAMP5's. But only 15 of 30 irregular cells are LAMP5 (not most), and the largest group is Lamp5 Plch2 Dock5 (8), not Ntn1 Npy2r (6). Both fail under both readings. 11 L1 VIP cells are irregular. The mouse tables are built only from the 250 cells with files, even under reading (b) (B5).
    • fig5d-mouse-pax6-doublets: the verifier’s outcome was “Not reproduced”. M c14: PAX6's sag_depol median is the highest, but its first_isi_inv_hero median (97.7, n=2) is below L1 VIP's (171). The missing fourth Lamp5 Krt73 cell is unexplained (B5).
  • Round 2
    2026-10-31
    Agreed with 39 of 41 outcomes. Independent agent run by CatalystNeuro (same harness, separate context, did not write the notebooks). Reviewed: Round 2. The full executed notebooks, with the conclusion cells, the summaries and the attempt record, the helper module and the claims file, with the paper. The verifier agreed with 39 outcomes and disagreed with two (fig2c-lamp5-gradient and fig6a-ephys-dprime-subclass-structure, which it would give as not_reproduced), asked for the sweep at rheobase + 40 pA to be checked for fig2c-subclass-ephys-differences, reported a possible misreading for fig5d-mouse-pax6-doublets, and listed sentences the outputs do not support. Report in transcripts/000630/verifier-2-report.md.
    • fig2c-lamp5-gradient: the verifier’s outcome was “Not reproduced”. Neither criterion names a partial level. The record changed fig4b-adarb2, fig4d and fig5d to not_reproduced on exactly that ground, so this claim should follow the same rule; sag misses 0.001 under every reading.
    • fig6a-ephys-dprime-subclass-structure: the verifier’s outcome was “Not reproduced”. Neither criterion names a partial level, and the record changed fig4b-adarb2, fig4d and fig5d to not_reproduced on exactly that ground, so this claim should follow the same rule; the second reading of high fails.
  • Round 3
    2026-10-31
    Agreed with 3 of 3 outcomes. Independent agent run by CatalystNeuro (same harness, separate context, did not write the notebooks). Reviewed: Round 3. Only the three proposed changes of outcome and the analysis behind them in the executed notebook, with the claims file and the paper. The verifier agreed with all three, for fig2c-subclass-ephys-differences on the condition that the assumption be recorded as a structured field. Report in transcripts/000630/verifier-3-report.md.

Method differences

How the tests differed from the paper’s method or data, and the claims each applies to.

  • Cell labels (t-type, subclass, layer, region, donor) come from the paper's cell table through the link claim dandiset-cell-link.patchseq-counts fig2c-subclass-ephys-differences fig2b-subclass-ephys-profiles figs3a-sag-adaptation fig2c-lamp5-gradient figs6-donor-condition-ephys figs6c-region-ephys fig4b-mc4r-sag-irregularity fig4b-adarb2-irregular-firing fig5b-tnfaip8l3-ephys fig6a-ephys-dprime-subclass-structure fig6d-gmm-subclass-f1 figs8a-classifier-cv fig3d-ephys-species fig3g-variability-dimensions fig4d-mouse-no-rosehip-ephys fig5d-mouse-pax6-doublets
  • Features follow the claims file's O1. Reading (a) uses the features computed here with IPFX 2.1.2 from the long square sweeps where they agree with the paper's aibs_features_E.csv within 1% for at least half of the cells (39 features, which agree within 1% for 53 to 98% of cells), and the paper's values for the others (custom features the paper did not release, ramp, short square and chirp features, and five adaptation ratios, which agree within 1% for only 4 to 37% of cells). Reading (b) uses the paper's values throughout. The 50% rule is an assumption of this attempt; the claims file's O1 does not say when a recomputed feature counts as computed. Two variants of reading (a) are shown, (a') with the features extracted without the Methods' 500 ms rms noise criterion, and (a, ratios) with the adaptation ratios computed here, for figs3a, fig6d and fig3g; neither changes an outcome except (a') for fig2c-subclass-ephys-differences, whose outcome rests on it.fig2c-subclass-ephys-differences fig2b-subclass-ephys-profiles figs3a-sag-adaptation fig2c-lamp5-gradient figs6-donor-condition-ephys figs6c-region-ephys fig4b-mc4r-sag-irregularity fig4b-adarb2-irregular-firing fig5b-tnfaip8l3-ephys fig6a-ephys-dprime-subclass-structure fig6d-gmm-subclass-f1 figs8a-classifier-cv
  • Features follow the claims file's O1. Reading (a) uses the features computed here with IPFX 2.1.2 from the long square sweeps where they agree with the paper's aibs_features_E.csv within 1% for at least half of the cells (38 features computed for both species; 39 for the human cells alone, which agree within 1% for 53 to 98% of cells), and the paper's values for the others (custom features the paper did not release, ramp, short square and chirp features, and five adaptation ratios, which agree within 1% for only 4 to 37% of cells). Reading (b) uses the paper's values throughout. The 50% rule is an assumption of this attempt; the claims file's O1 does not say when a recomputed feature counts as computed. Two variants of reading (a) are shown, (a') with the features extracted without the Methods' 500 ms rms noise criterion, and (a, ratios) with the adaptation ratios computed here, for figs3a, fig6d and fig3g; neither changes an outcome except (a') for fig2c-subclass-ephys-differences, whose outcome rests on it.fig3d-ephys-species fig3g-variability-dimensions fig4d-mouse-no-rosehip-ephys fig5d-mouse-pax6-doublets
  • Tested on the paper's deposited morphology features.fig4b-mc4r-axon fig5b-tnfaip8l3-dendrites
  • The match uses the LIMS number, as no file names its t-type or the table's specimen id.dandiset-cell-link
  • Assumed that the paper's sweep QC did not exclude the sweeps that fail here only the Methods' rms noise criterion of 0.5 mV over 500 ms (Methods, Quality control) as IPFX measures it, so the outcome is judged on variant (a'), extracted without that criterion. This departs from the Methods' QC as IPFX measures it. The paper's own per-cell values were computed from such sweeps (7 of the 9 fallback cells that disagree with the paper), and without the criterion 38 of the 39 recomputed features agree with the paper's values for more cells (median share within 1% 0.933 against 0.895). With the criterion as written (reading a) the claim is partially reproduced (first_isi_inv_hero FDR p 4.7e-7); on the paper's values (reading b) it holds (1.7e-8). How the paper measured this noise is asked of the authors (findings, methods_unavailable).fig2c-subclass-ephys-differences
  • Sweep QC follows the Methods as far as the files allow (leak within 100 pA, rms noise below 0.2 mV over 1.5 ms and 0.5 mV over 500 ms, IPFX's integrity check, and sweeps stored with zeros before the end of the stimulus left out); the Methods' criterion of a baseline within 2 mV of target is not applied, as the files do not state the target.fig2c-subclass-ephys-differences
  • Dunn's post hoc tests as the Methods and legend say; the code's Mann-Whitney post hoc is computed as a variant.fig2c-subclass-ephys-differences
  • The adaptation ratio is computed here on the lowest long square with at least 4 spikes (Methods); it agrees with the paper's value within 1% for 19% of cells (median difference 2.7%), so reading (a) uses the paper's ratio with sag computed here, and the regression on the ratio computed here, in both orders, is a variant.figs3a-sag-adaptation
  • The dandiset lacks the Amsterdam and Szeged LAMP5 cells the code includes; the test runs on the Seattle cells, and the three-site test is a variant using the paper's per-cell features for the other sites.fig2c-lamp5-gradient
  • The table's medical_conditions, donor_sex and donor_age stand in for the LIMS donor records the code reads, as the criterion says; 108 of 194 cells have no medical condition in the public table.figs6-donor-condition-ephys
  • input_resistance_ss is not computed here and is the paper's value under both readings.figs6c-region-ephys
  • The irregularity ratio (ir_late_mean) is custom code the paper did not release; it is the paper's value under both readings.fig4b-mc4r-sag-irregularity
  • ir_late_mean, sag_peak_t and sag_tau are not computed here and are the paper's values under both readings.fig4b-adarb2-irregular-firing
  • postap_slope_rheo and adp_v_last_rheo are custom features the paper did not release; they are the paper's values.fig5b-tnfaip8l3-ephys
  • Random forest seeds 0, 1 and 2 are a standard choice; the code sets none.fig6a-ephys-dprime-subclass-structure
  • Choosing features by site uses the Amsterdam and Szeged feature tables of the paper's code (tamas_features_E.csv, mansvelder_features_E.csv); those cells are not in the dandiset and are used only for this choice.figs8a-classifier-cv
  • Repeated stratified 5-fold cross-validation with 10 repeats and seed 0 (scikit-learn defaults; the seed is a standard choice).figs8a-classifier-cv
  • AP height at the ramp (peak_deltav_ramp) is not computed here and is the paper's value for both species.fig3d-ephys-species
  • Mouse cells from DANDI 000020 version 0.210913.1639 with the paper's mouse labels; 250 of 272 strict mouse L1 cells have a file there.fig3d-ephys-species
  • Mouse VISp cells as the claims file says; the code's mouse set takes every visual area (VIS), shown as a variant.fig3d-ephys-species
  • A subclass with fewer than 2 cells of either species with a value is left out of that feature's ANOVA, as the HC3 errors are undefined with one cell; with VISp this leaves out PAX6 (1 mouse cell) for every feature.fig3d-ephys-species
  • Mouse cells from DANDI 000020 version 0.210913.1639; 250 of 272 strict mouse L1 cells have a file there, 205 of them in VISp.fig3g-variability-dimensions
  • ir_late_mean is the paper's value (custom code not released).fig4d-mouse-no-rosehip-ephys
  • 22 of the paper's strict mouse L1 cells (20 in VISp layer 1) have no file in DANDI 000020.fig4d-mouse-no-rosehip-ephys
  • sag_depol is the paper's value (custom code not released).fig5d-mouse-pax6-doublets
  • Tested on the paper's per-cell morphology features as deposited in its code archive, not recomputed from the reconstructions in the Brain Image Library.fig2d-subclass-morphology
  • The claims file gives no criterion; the claim was judged on the three features of Fig. 2D (l1_subclass_distinctness.ipynb cell 21) having FDR p < 1e-3.fig2d-subclass-morphology
  • Judged on FDR p < 1e-4 for both features, the threshold of the Fig. 4B legend.fig4b-mc4r-axon
  • Judged on FDR p < 0.05 (Fig. 5B legend) with TNFAIP8L3 higher for both features, and each cell's extent over 550 um.fig5b-tnfaip8l3-dendrites

Provenance

Attempt record
000630-chartrand-2023-01
Paper
10.1126/science.adf0805
Date
2026-10-31
Made by
An agent, run by CatalystNeuro
Dataset
DANDI:000630
Version
0.230915.2257 (doi:10.48324/dandi.000630/0.230915.2257)
Run on
GitHub Actions
Harness
Claude Code
Model
claude-opus-5-5
Protocol
pilot-12

Transcripts of the agent runs

Each run’s prompt, messages and tool calls, with long output cut and the text of the paper left out, and its final report.