Dandiset 001933

Reproducing Chen, He et al. (2026) from dandiset 001933 18

Notebook reproduce_chen_2026.ipynb

• ✕Not reproducedFigure 6C to 6F, Supplementary Figures 7B, 7C, 8C to 8E; Source Data (Zenodo 10.5281/zenodo.19930567)uses data from outside the dandiset

  The dandiset's recordings are those behind the paper's Figure 6 and Supplementary Figures 7 and 8, and the paper's published per-stimulation traces, evoked integrals and spontaneous transient integrals can be recomputed from them.

  All 27 mice of the source data are in the dandiset with the same genotype and line. The Anxa1 half links. 120 of 120 traces of Figure 6C and 479 of 480 of Supplementary Figure 7B equal the dandiset's dF/F from 1 s before onset (largest difference among matched traces 5.7e-13 in each), the evoked integrals equal the code's measure times 0.0001 for all Anxa1 records but one, and the transient counts match for 15 of 15 mice. The one miss in each is the last 4 mW stimulation of mouse 4398, whose processed series ends 0.8 s after onset. The Calb1 half does not link; 0 of 384 traces, 0 of 384 integrals and the transient counts of 1 of 12 mice match. dF/F recomputed from the raw signal with the code's processing reproduces the stored Calb1 series (largest difference 1.47 % dF/F) but not the published traces (median differences 66 to 519 % dF/F; 22 to 88 at the best background fraction per mouse). The published spontaneous values are 0.005 times the trapezoid integral of each transient divided by its number of samples (within-mouse spread of the ratio at most 2.2e-15; 15 of 15 Anxa1 mice and 0 of 12 Calb1 mice match at 1e-4), so part (4) as fixed, with integrals, matches for no mouse at either tolerance. The four parts match for 1.0, 0.609, 0.609 and 0 of their records, so the outcome is not reproduced. With the published measure in part (4) they match for 1.0, 0.609, 0.609 and 0.556, which would be partially reproduced; the criterion fixed integrals, so this is a variant. The mean dF/F over each transient comes close (13 of 15 Anxa1 mice within 1%, none within 1e-4). The Calb1 mismatch is not one of epoch or power labels; searched over all 64 epochs and 8 powers of each mouse, no epoch is within 1e-6 of any of the 384 S8D traces (closest 15.7 to 150.8 % dF/F), and against the matched epochs the per-mouse median slopes are 0.21 to 0.75 and offsets -13.8 to 16.2 % dF/F. The Figure 6E integrals match the 0.5 mW epochs (120 of 120) and none of the 4 mW ones. The published values reproduce the paper's statistics (Figure 6E p = 1.1e-20, Figure 6F p = 2.75e-177, Cohen's d 2.06 and 0.765), so the Calb1 differences come from the data, not from the paper's computation on them.

  How the test differed from the paper’s method

  • The criterion fixed the integral of each spontaneous transient; the published values turned out to be 0.005 times the integral divided by the number of samples in the transient. That measure, and the mean dF/F, are shown as variants and do not change the outcome.
• ✕Not reproducedResults, last section

  The G2019S reduction of evoked release at 0.5 mW is much larger for Anxa1+ (Cohen's d = 2.05) than for Calb1+ stimulation (d = 0.76).

  Anxa1 d = 2.21 is within tolerance; Calb1 d = 1.40 is not (0.684 to 0.836), and the ratio 1.58 is under the factor of 2 the criterion asks. With the code's window, 2.06 and 1.25. The paper's published integrals give 2.06 and 0.765, so the miss is consistent with the Calb1 dF/F in the dandiset not being the paper's. The Anxa1 effect is larger than the Calb1 effect at every power and window that starts by onset (ratio 1.29 to 1.74), so the direction of the paper's comparison holds, with a smaller gap.

  How the test differed from the paper’s method

  • Run on the dandiset's Calb1 dF/F, which differs from the trace behind Supplementary Figure 8.
• ✕Not reproducedFigure 2A to 2Cdata in PRIDE PXD065006

  LRRK2 kinase inhibition with MLi-2 changes 289 phosphopeptides in striatal synaptosomes of G2019S mice, including RAB3 T86.

  On the log2 abundances as deposited, 1694 (reading a, all six values) or 1810 (reading b, two per group) phosphopeptides pass p <= 0.05 and |difference| > 0.58, against 289, and nearly all are lower with vehicle (1673 and 1785), as the samples labelled MLi-2 have higher abundances overall (median log2 17.84 to 18.12 against 17.25 to 17.47). The RAB3 T86 peptide passes (p = 0.00892) but is lower with vehicle (difference -1.31), so neither part of the criterion holds. Centring each sample on its median, a step the criterion did not fix, gives 243 and 282 peptides (282 within tolerance) and RAB3 T86 still higher with MLi-2 (difference -0.693, p = 0.0238). The paper's volcano table holds MLi-2 minus vehicle as the samples are labelled; on the 4340 peptides with all six values its difference equals that difference plus a constant to within 1.6e-06, and against vehicle minus MLi-2 the residual reaches 13. Its p-values are near those of a t-test on median-centred values but not equal (median gap in -log10 p 0.0088 Welch, 0.0161 Student). It gives 254 peptides at the legend's thresholds, and RAB3 T86 +0.688, which the legend reads as higher with vehicle. As the samples are labelled, the RAB3 T86 phosphopeptide rises after MLi-2. RAB10 T73 does not change (0.15, p = 0.775), so the data cannot tell whether the labels or the figure's direction are swapped. If the labels are swapped, the median-centred reading b gives 282 peptides and RAB3 T86 higher with vehicle (+0.693), which would reproduce the claim, so the outcome rests on a labelling question the data cannot answer. Attempt -01 blocked this claim with data_missing under pilot-6; under pilot-7 it is tested on the PRIDE data.

  How the test differed from the paper’s method

  • The criterion fixed log2 abundances without normalisation; the paper's volcano table follows median-centred values. The median-centred result is shown as a variant and does not change the outcome.
  • The legend does not say which peptides were tested; two readings (all six values, two per group) are shown.
  • The search (Proteome Discoverer with Byonic and Sequest, commercial) is not re-run; the test starts from the deposited abundances.
• ◐Partially reproducedFigure 6F (right) and legend; Results, last section

  Six of eight individual G2019S mice show significantly smaller spontaneous dopamine transients than the WT group; mice 4651 and 3743 do not.

  By the integral 5 of 8 GS mice are below the WT group under every reading; the exceptions are 3743 (p = 0.431), 4651 (mean 417, above the WT mean of 303) and 4652 (p = 0.0128). With the paper's measure, 0.005 times the integral divided by the number of samples, the one-tailed Student test gives 6 of 8 with 3743 and 4651 as the exceptions and the legend's p-values (3742 5.28e-88, 4004 1.24e-95, 4652 6.21e-13, 4885 1.44e-49; 4651 0.00844 against 0.008); the Welch tests give 7 there. The difference from the paper comes from the measure; the paper's count follows the Student test of its legend.

  How the test differed from the paper’s method

  • The integral of each transient is used, as the Methods state; the paper's measure is shown as a variant.
• ◐Partially reproducedSupplementary Figure 8E (right); Results, last section

  Only 2 of 7 G2019S mice show reduced Calb1+ evoked dopamine release relative to the WT group.

  At 0.5 mW, 7 (Welch one-tailed), 6 (Welch two-tailed) and 4 (Student, either tail) of 7 GS mice are below the WT group at p < 0.05/7, against the paper's 2; the closest reading gives 4, recorded as measured. Student tests give 2 at 0.1 and 1 mW. The panel's power is not stated, and the dandiset's Calb1 dF/F is not the paper's.

  How the test differed from the paper’s method

  • The legend does not state the power of the per-mouse panel; 0.5 mW was fixed before the analysis and the other powers are shown.
  • Run on the dandiset's Calb1 dF/F, which differs from the trace behind Supplementary Figure 8.
• ◐Partially reproducedFigure 3D to 3Fverifier disagreed at firstdata in PRIDE PXD065125

  RIM1 and RIM2 bind unphosphorylated RAB3A in preference to RAB3A phosphorylated at T86, while RILPL1 and RILPL2 prefer the phosphorylated form.

  RIM1 (Q99NE5-7) and RIM2 are higher with RAB3A (log2 differences 2.42 and 2.17, paired p = 0.00361 and 0.0124) and RILPL1 higher with p-RAB3A (-6.02, p = 9.8e-05). RILPL2 is detected in all six p-RAB3A and in none of the RAB3A pulldowns, so the criterion's paired test has no pair and does not find it higher with p-RAB3A; three of four comparisons hold. With the Methods' imputation (seeded), a variant, it is higher with p-RAB3A (-7.92, p = 1.21e-08), and the limma table gives logFC -7.58, so the data point the way of the claim for RILPL2. The paper's p-values for RIM2 and RILPL1 (0.011, 0.002) are those of the paired test on intensities without the log (0.0109, 0.0022). The deposited limma table agrees in direction for every group. Its counts at the text's p-value < 0.05 and |log2FC| >= 1 are 121 and 32; the paper's 69 and 16 are the counts at adjusted p < 0.05. Attempt -01 blocked this claim with data_missing under pilot-6; under pilot-7 it is tested on the PRIDE data.

  How the test differed from the paper’s method

  • RILPL2 has no pair for the criterion's paired test and is counted as not holding; the Methods' imputation followed by an unpaired t-test, which gives four of four, is shown as a variant.
  • The tests use log2 intensities; the paper's p-values follow intensities without the log. Both are shown.
  • Replicates are paired in run order, as the paper does not give the pairing.
• ◐Partially reproducedFigure 4D and 4Edata in BioImage Archive S-BIAD2074 (images); Zenodo doi:10.5281/zenodo.19930567 (per-area values)

  Fewer TH+/VAMP2+ striatal synaptosomes from G2019S mice contain bassoon, and the remaining bassoon clusters are larger.

  Part A holds. In the source data fewer TH+/VAMP2+ synaptosomes contain bassoon in GS (12.0 against 21.4 %, p = 6.38e-05; 0.000118 without the GS value under 1 %) and the bassoon area is larger (0.0862 against 0.0750 um2, p = 0.0301, the paper's value); with one value per mouse p = 0.263 and 0.474. Part B does not. The Methods' FIJI procedure as re-implemented here gives, GS against WT, 48.8 against 52.4 % with bassoon (p = 0.459) and a bassoon area of 0.0682 against 0.0696 um2 (overlap, p = 0.805) or 0.132 against 0.141 um2 (bassoon particle, p = 0.206). The re-implementation keeps a median of 183 VAMP2 particles per image against the legend's about 1000; the Default threshold alone gives a median of 1186 objects, of which the size limit keeps 193 and the circularity limit 183. Its percentages are more than twice the paper's, so part B may fail because of this attempt's segmentation, and its null result is weak evidence against the claim. The OME metadata of 165 of 168 images confirm the channel order. Attempt -01 blocked this claim with data_missing under pilot-6; under pilot-7 it is tested on the Zenodo values and the BioImage Archive images.

  How the test differed from the paper’s method

  • The FIJI procedure is re-implemented in Python (rolling ball as ImageJ shrinks it, ImageJ's Default threshold, scikit-image perimeters); it is not FIJI, and its particle counts are far below the paper's.
  • The images cannot be matched to the published areas one by one; part B compares genotypes over the deposited images (35 GS and 39 WT for the percentage, 49 and 43 for the area, one image in each folder with nothing to measure).
• ◐Partially reproducedFigure 5D, 5E, 5G and 5Hdata in BioImage Archive S-BIAD2071 (images); Zenodo doi:10.5281/zenodo.19930567 (per-section values)

  Bassoon cluster density is reduced and cluster volume increased in Aldh1a1+ but not Aldh1a1- dopamine axons of G2019S mice, and the same holds in Anxa1+ axons.

  Five of six parts hold. With section 5 of WT mouse 1723 counted once (its four values equal those of section 4), Aldh1a1+ density is lower in GS (0.164 against 0.217) at Sidak p = 0.058, so part 1 fails; Aldh1a1- density does not differ (p = 0.713); bassoon volume is larger in GS Aldh1a1+ axons (p = 0.0425) and not in Aldh1a1- axons (p = 0.699); in Anxa1+ axons density is lower (p = 0.0374) and volume larger (p = 0.0148). As deposited, with the section twice, all six hold and the ANOVA gives the legend's numbers (5D Sidak p 0.0344, 5E 0.0385). Attempt -01 blocked this claim with data_missing under pilot-6; under pilot-7 it is tested on the Zenodo values.

  How the test differed from the paper’s method

  • The analysis starts from the per-section values; the 542 GB of SIM images (S-BIAD2071) are matched by file name and not analysed again, as the Methods' analysis runs in Imaris 10.1.
  • One section that appears twice in the source data is counted once, as the claims file fixes; the paper counts it twice.
• ✓ReproducedFigure 6E (left), Results, last section

  Optogenetically evoked dopamine release in the dorsolateral striatum (Anxa1+ projection region) at 0.5 mW is lower in LRRK2-G2019S than in LRRK2-WT mice (64 against 56 stimulations, p = 1.10e-20, one-tailed two-sample t-test).

  Light-on integrals at 0.5 mW, GS 48.8 against WT 128.0 % dF/F x s, one-tailed p = 1.16e-22 (paper 1.10e-20), Cohen's d 2.21. The code's window gives p = 1.1e-20, the paper's value. It holds at 4 mW (p = 4.08e-18), without the two GS mice given 0.33 s trains (p = 4.16e-17), and with mouse means (Welch p = 0.000434). The window chunking_index.m computes as written reverses the sign (p = 1).

  How the test differed from the paper’s method

  • The integral is over each train's light-on period, as the Methods state; the paper's values come from the code's window, -0.1 to 1.0 s, shown as a variant. The baseline, which the Methods do not give, is the code's.
  • The paper's plotting code selects power code 'h' for this panel; the panel is tested at the 0.5 mW of the legend, which the source data confirm, and 4 mW is shown as a variant.
• ✓ReproducedFigure 6E (right) and legend; Results, last section

  Seven of eight individual G2019S mice show significantly reduced evoked dopamine release at 0.5 mW compared with the WT group; mouse 3743 does not.

  Under all four readings (Welch or Student, one- or two-tailed) 7 of 8 GS mice are below the WT group at p < 0.05/8 and 3743 is the exception (mean 125 against 128, Welch one-tailed p = 0.362). The count is the same with the code's window. Two of the seven, 3742 and 4885, received the paper's powers as 0.33 s trains, unlike every WT mouse, and their responses do not follow the labelled power; the other five significant mice were stimulated as the WT mice were.

  How the test differed from the paper’s method

  • The Methods name Welch's test, the legend's p-values are one-tailed and the code runs a two-tailed Student test; all four readings are shown and all give 7.
• ✓ReproducedSupplementary Figure 7C; Results, last section

  The reduction of evoked dopamine release in Anxa1 G2019S mice holds at each of the four stimulation powers, 0.1, 0.5, 1 and 4 mW (p from 1.29e-15 to 1.10e-20).

  GS lower at all four powers, one-tailed p from 3.13e-15 to 1.16e-22 with the light-on window. With the code's window the p-values at 0.1, 0.5 and 1 mW equal the paper's (1.29e-15, 1.1e-20, 1.22e-17); at 4 mW it is 5.62e-16 against 2.39e-16, as that window, which runs to 1.0 s after onset, leaves 55 WT stimulations there (the processed series of mouse 4398 ends 0.8 s after its last onset). The Methods window keeps all 56.

  How the test differed from the paper’s method

  • In the code's window variant, 55 WT stimulations at 4 mW in place of 56, as one falls at the end of a truncated series.
• ✓ReproducedFigure 6F (left) and legend

  Spontaneous dopamine transients in the dorsolateral striatum are smaller in G2019S than in WT mice (1064 against 798 transients, p = 2.75e-177, one-tailed two-sample t-test), with 57 to 285 transients per mouse.

  The Methods' detection gives the paper's counts exactly (1064 and 798, 57 to 285 per mouse). Integrals GS 131.9 against WT 302.9 % dF/F x s, one-tailed p = 4.85e-72 (paper 2.75e-177). With the measure of the published values, 0.005 times the integral divided by the number of samples, p = 2.747e-177, the paper's value. With mouse means, Welch p = 0.0318.

  How the test differed from the paper’s method

  • The integral of each transient is used, as the Methods state; the paper's values are 0.005 times the integral divided by the number of samples in the transient, shown as a variant.
• ✓ReproducedSupplementary Figure 8C; Results, last section

  In the dorsomedial striatum (Calb1+ projection region), spontaneous dopamine transients are not reduced in G2019S mice (970 against 682 transients, p = 0.98).

  The paper's test does not find the effect, one-tailed p = 0.0509, difference of means 21.1 % dF/F x s, Cohen's d 0.085; the result sits at the threshold and is fragile. Moving either end of the exclusion window by up to 10 samples gives p from 0.0403 to 0.0792, below 0.05 in 59 of 121 windows. With the published measure (0.005 times the integral divided by the number of samples) GS are lower at p = 2.45e-09 (d 0.305), with the transient mean at p = 2.25e-09, with the code's exclusion window as written at p = 1.81e-05, and with mouse means Welch p = 0.402. The counts are within tolerance but differ from the paper's 970 and 682, and the Calb1 dF/F in the dandiset is not the one the paper analysed (source-data-link); the published values give p = 0.989.

  How the test differed from the paper’s method

  • Run on the dandiset's Calb1 dF/F, which differs from the trace behind Supplementary Figure 8.
• ✓ReproducedSupplementary Figure 8E (left); Results, last section

  Evoked dopamine release in the dorsomedial striatum from Calb1+ neuron stimulation is reduced in G2019S mice at each of four powers (56 against 40 stimulations per power, p from 6.45e-05 to 0.001).

  GS lower at all four powers, one-tailed p from 4.38e-07 to 6.29e-10, smaller than the paper's 6.45e-05 to 0.001. The p-values differ because the dandiset's Calb1 dF/F is not the paper's (source-data-link). With one value per mouse (7 GS, 5 WT), Welch one-tailed p is 0.0424, 0.0413, 0.0726 and 0.0916 at 0.1, 0.5, 1 and 4 mW.

  How the test differed from the paper’s method

  • Run on the dandiset's Calb1 dF/F, which differs from the trace behind Supplementary Figure 8.
• ✓ReproducedFigure 1B and 1Ddata in BioImage Archive S-BIAD2070 (images); Zenodo doi:10.5281/zenodo.19930567 (per-section values)

  LRRK2 immunolabeling intensity is higher in Aldh1a1+ (vulnerable) than in Aldh1a1- SNc dopamine neurons (p = 0.0008).

  Over the 16 sections of the source data (5, 6 and 5 from three mice), LRRK2 intensity is higher in Aldh1a1+ than in Aldh1a1- neurons, 1.049 against 0.973, two-tailed unpaired Student p = 4.65e-06, Cohen's d 1.97; higher in 15 of 16 sections and in each mouse. The paper's p = 0.0008 matches a paired test over sections (0.000759) or an unpaired test of the three mouse means (0.000822), not the unpaired test over sections its legend names. Attempt -01 blocked this claim with data_missing under pilot-6, as the data are not in the dandiset; under pilot-7 it is a claim on data elsewhere and is tested.

  How the test differed from the paper’s method

  • The test starts from the paper's per-section values. The images (S-BIAD2070) are matched by mouse but not segmented again, as the Methods' analysis runs in Imaris 10.1, a commercial program, with automatic thresholds.
• ✓ReproducedFigure 2D to 2Gdata in Zenodo doi:10.5281/zenodo.19930567

  Phosphorylation of RAB3A and RAB3C is increased in the SNc of G2019S mice and returns to WT levels with MLi-2.

  With contrasts on the pooled variance, Sidak-adjusted over the three pairs, GS is above WT and above GS with MLi-2 for RAB3A (p = 0.0202 and 0.00688) and RAB3C (0.00358 and 0.0415), with F = 8.593, 11.33, 14.76 and 7.398, the legend's values. GS with MLi-2 does not differ from WT (adjusted p = 0.963 and 0.622). Over two pairs the p-values are 0.0135, 0.00459, 0.00239 and 0.0279. Attempt -01 blocked this claim with data_missing under pilot-6; under pilot-7 it is tested on the Zenodo data.

  How the test differed from the paper’s method

  • The test starts from the deposited ratios; the uncropped blots are not quantified again, as the Methods do not say how bands were measured.
  • The legend's two-way ANOVA has genotype and treatment factors on three groups; it is run as the equivalent one-way model with contrasts, which gives the legend's F values.
• ✓ReproducedFigure 4H to 4Ldata in Zenodo doi:10.5281/zenodo.19930567

  RIM1 is reduced in striatal synaptosomes of G2019S mice (p = 0.0245) but not in other striatal fractions or the SNc.

  RIM1 in synaptosomes is lower in GS, 0.206 against 0.319, two-tailed p = 0.0245 (the paper's value), Cohen's d -1.53. RIM1 in the S1 fraction (p = 0.896) and in the SNc (p = 0.936) does not differ, nor do synaptophysin (4G, p = 0.445) and the protein of 4H (p = 0.634). Attempt -01 blocked this claim with data_missing under pilot-6; under pilot-7 it is tested on the Zenodo data.

  How the test differed from the paper’s method

  • The test starts from the deposited band values; the uncropped blots are not quantified again, as the Methods do not say how bands were measured.
• ✓ReproducedFigure 5I and 5Jdata in BioImage Archive S-BIAD2072 (images); Zenodo doi:10.5281/zenodo.19930567 (per-section values)

  The volume occupied by TH+ fibres in the dorsal striatum does not differ between G2019S and WT mice.

  The paper's test does not find a difference in TH volume, two-tailed p = 0.117 over 12 sections per genotype; GS is 7.1 % lower (0.929 against 1.000), Cohen's d -0.67. Attempt -01 blocked this claim with data_missing under pilot-6; under pilot-7 it is tested on the Zenodo values.

  How the test differed from the paper’s method

  • The test starts from the per-section values; the images (S-BIAD2072) are matched by file name and not analysed again, as the Methods' analysis runs in Imaris 10.1.