Cutaneous manifestations in Costello syndrome: HRAS p.Gly12Ser affects RIN1-mediated integrin trafficking in immortalized epidermal keratinocytes.
The main results reproduced, with only marginal, non-material deviations.
Every item that counted toward this verdict, and the exact part of the reproduction that produced it.
- ✓Same input data as the authors
- ✓Reported values were directly comparable
- 🔴A deviation arose in the data or preprocessing
- 🔴A deviation was attributed to the published material
- 🟡Reported values were not (fully) derivable from the shared data
- 🟡The deviation was non-trivial in magnitude
- 🟡The central claim did not (fully) hold under reproduction
- 🟡Overall, the reproduction showed a material discrepancy
A 0–100 reproducibility-quality score from the per-question grades, shown as a z-score: standard deviations above (+) or below (−) the mean of comparable assessments.
▸Reproduction agent’s raw note
described-well-enough = partly. This is a wet-lab mechanistic Costello-syndrome paper with ONE pipeline-derived dataset: a quantitative AP-MS proteomics table (Supplementary Table S1, HA-HRAS-WT vs -Gly12Ser vs HaCaT/EV controls). No raw MS data and no analysis code were deposited (no ProteomeXchange/PRIDE/MassIVE, no GitHub), so upstream Proteome Discoverer quantification is out of reach; downstream multivariate outputs are reproducible from the public table by applying the third-party ClustVis/pcaMethods recipe (BRIEF rule P16). Ran on «our HPC» (SLURM «job», pcaMethods NIPALS). REPRODUCED: dataset N exactly (885 proteins), PCA genotype separation, Fig 1B Pearson clustering of WP_RAS_SIGNALING (structure), and RIN1 as the top HRAS effector by enrichment. NOT REPRODUCED: the reported Fig 1A 'PC1 = 78%' — faithful NIPALS gives 35-44%, and the reported PC1+PC2 = 105% is mathematically impossible, flagged as a value not derivable from the shipped data (likely a tool-display artifact or a PCA run on a fuller replicate set than the 6 columns released). NOT ATTEMPTED: all wet-lab experiments (effector Kd, integrin trafficking, endosome/RAB5/adhesion/immunoblots).
These records describe the outcome of reproduction attempts carried out autonomously by brainbox using large language models (LLMs). They are not peer review, not an audit, and not a determination of error or misconduct by any author. A verdict reflects what one attempt could or could not reproduce — which may depend on data access, undocumented parameters, the computing environment, or the depth of effort — and not a judgement of the people who did the work. We can be wrong, and we correct mistakes quickly: every record carries a “report an error” button.
Assessment versions
Every reproduction run is kept as an immutable version — anchored to the data as it stood, with a tamper-evident chain hash. A rerun (e.g. after an author updates a deposit) adds a new version; the previous one stays on record.
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v1 current initial assessment Score 66assessed: 2026-06-19 ⛓ 38ad45f513d4
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Updated or fixed a deposit, or is there an erratum? Ask us to re-run the metrics. We verify by email first; the new result is published as a new version with full history — nothing is overwritten.
Provenance — full disclosure
When this reproduction was carried out, which methodology version was used, and by whom — so the record can be audited and checked independently.
- Reproduced
- 2026-06-19
- Rubric version
- v1.0
- Assessed by
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🤖 AI curator · claude (ai-curator room) · v1.0 · run #1 2026-06-19no human curator yet
- Last updated
- 2026-08-05
Provisional, curator- or AI-assessed, and independently checkable. A reproduction outcome states what one attempt could reproduce — not a judgement of the authors.
What was reproduced
The exact results taken into scope, with each reported value next to the value our attempt produced.
Scope — pmid-35981076
Paper: Nauth T, Bazgir F, Voß H, et al. "Cutaneous manifestations in Costello syndrome: HRAS p.Gly12Ser affects RIN1-mediated integrin trafficking in immortalized epidermal keratinocytes." Hum Mol Genet 2023;32(2):304–318. DOI 10.1093/hmg/ddac188. PMID 35981076.
Nature of the study
Mechanistic cell-biology paper. A single quantitative affinity-purification mass-spectrometry (AP-MS) proteomics experiment underpins the discovery part; the rest of the paper (Figs 2–7, S2–S14) is wet-lab (microscopy, endosome co-localisation, fluorescence-polarisation Kd, RAB5 GEF assays, immunoblots, adhesion assays).
Data / code availability
- No raw MS data deposited. No ProteomeXchange/PRIDE/MassIVE accession in the
article, in Europe PMC
datalinks(only GlyGen + Altmetric), or in a PRIDE keyword search (Nauth/Rosenberger/HaCaT/HRAS → 0 hits). Not in PMC (no PMCID). - No analysis-code repository (no GitHub/Zenodo).
- Processed proteomics IS public as Supplementary Table S1
(
nauth_bazgir_et_al_hras-rin1_tab_s1_ddac188.xlsx, openly downloadable from OUP): 885 quantified proteins × 6 sample columns of log2 relative abundance (HaCaT, EV, HA-HRAS^WT clone1/2, HA-HRAS^Gly12Ser clone1/2) plus t-test/ANOVA columns. This is the input to the in-scope downstream pipeline outputs.
Pipeline used by the authors (from Methods)
- MS identification/quantification: Proteome Discoverer v2.4 + Sequest, SwissProt human (Apr 2020, 20,365 entries), FDR < 0.01. (Not reproducible — raw spectra not deposited.)
- Downstream multivariate analysis (Fig 1A NIPALS PCA, Fig 1B Pearson-correlation
hierarchical clustering of a named MSigDB gene set) = the visual/statistical
signature of ClustVis (biit.cs.ut.ee/clustvis; wraps R
pcaMethodsNIPALS). The reported "PC1 78% + PC2 27% = 105% > 100%" is the known ClustVis/NIPALS artifact on data with missing values. Reproducible from Table S1.
IN SCOPE (pipeline-derived, attempted)
| id | result | paper location | pipeline |
|---|---|---|---|
| C1 | 885 proteins quantified in HRAS AP-MS | Results / Table S1 | PD2.4 output (count check) |
| C2 | Fig 1A NIPALS PCA: PC1 = 78% explained variation; samples separate by genotype | Fig 1A + legend | ClustVis / pcaMethods NIPALS on Table S1 |
| C3 | Fig 1B Pearson-correlation hierarchical clustering of WP_RAS_SIGNALING proteins | Fig 1B + legend | ClustVis hierarchical clustering on Table S1 |
| C4 | RIN1 = quantitatively most prominent / high-affinity HRAS effector (enriched in HRAS precipitate) | Results (RIN1 definition) | ranking of AP-MS enrichment in Table S1 |
OUT OF SCOPE (wet-lab / not pipeline; not attempted)
- Upstream MS identification (raw spectra not deposited → cannot re-run PD2.4).
- Fluorescence-polarisation effector Kd / affinity ranking (Fig S2, wet-lab biophysics).
- All integrin-trafficking imaging, endosome co-localisation, RAB5 GEF activity, adhesion/recycling assays, immunoblots (Figs 2–7, S3–S14).
Reproduction approach
Apply the third-party tool / its underlying library (pcaMethods NIPALS +
Pearson-correlation hierarchical clustering, the ClustVis recipe) to the paper's
own Supplementary Table S1 on «our HPC», and compare the resulting PC1 %, the
sample-separation structure, the gene-set cluster, and the RIN1 enrichment rank
against the reported values. Per BRIEF rule P16, applying an existing third-party
tool to the paper's data is a fully valid reproduction.
Assessments & scoring basis
Each contributor’s verdict, the per-question basis, and the auditable, itemised worksheet behind it.
An automated assessment. It can flag an open question for review but can never, on its own, record a discrepancy verdict (C5) against a paper.
Every item that counted toward this verdict, and the exact part of the reproduction that produced it.
The single in-scope computational dataset (AP-MS Table S1) reproduces well: N=885 exact, genotype separation, WP_RAS clustering structure, and RIN1 as the #1 detected HRAS effector all hold. The one numeric anomaly is on the authors' side — Fig 1A reports PC1=78% and PC2=27% (sum 105%, impossible), and 78% is not derivable from the deposited table by any faithful NIPALS recipe (we get 35–44%); it is flagged as a likely tool-display artifact or a PCA run on undeposited replicates rather than asserted fabrication. Severity is moderate because this is a secondary descriptive label, not the central finding, and the paper's true mechanistic conclusion (RIN1–integrin trafficking) is wet-lab and out of scope, leaving core-claim confirmation limited. Overall a solid-with-caveats yellow.
Automated reproduction checks whether a published result can be regenerated from the paper’s described methods and shared data. When something does not reproduce, that is not a claim of error or misconduct — most often it reflects under-described methods, software or environment differences, or gaps in data access, and some of the pre-print papers in the queue may carry issues their authors had no part in. The goal is shared awareness that rigorous, fully-described methods help everyone — never a judgement of any author.
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Reproduction footprint
claude-opus-4-8Measured resources invested to assess this paper — sanitised (machine class only, no job ids/paths). Compute = HPC accounting (SLURM); tokens = the AI agent's session.