Oncogenic HRAS mutations cause prolonged PI3K signaling in response to epidermal growth factor in fibroblasts of patients with Costello syndrome.
Part of the results reproduced; minor but material deviations remained.
Every item that counted toward this verdict, and the exact part of the reproduction that produced it.
- ✓No relevant deviation in data/preprocessing
- ✓Any deviation was negligible
- 🔴Could not use the authors’ exact input data
- 🔴Reported values were only indirectly comparable
- 🔴A deviation was attributed to the published material
- 🟡Reported values were not (fully) derivable from the shared data
- 🟡The central claim did not (fully) hold under reproduction
- 🟡Overall, the reproduction showed a material discrepancy
▸Reproduction agent’s raw note
DROP (non_pipeline) - INDEPENDENTLY RE-VERIFIED on 2026-06-22 (this room is a requeue of a prior, well-founded drop). PMID 19035362 = Rosenberger, Meien & Kutsche, Human Mutation 2009;30(3):352-62, DOI 10.1002/humu.20855: 'Oncogenic HRAS mutations cause prolonged PI3K signaling in response to EGF in fibroblasts of patients with Costello syndrome.' Confirmed against the live PubMed record: a primary-cell wet-lab signal-transduction study (CS-patient vs control skin fibroblasts; active-RAS/RAS-GTP pulldown, EGF time-course, SDS-PAGE/immunoblotting with densitometry, PI3K-inhibitor pharmacology). It has NO sequencing/microarray/omics data, NO GEO/SRA/ArrayExpress/figshare/zenodo accession, NO code repository, and NO bioinformatic pipeline (PubMed/Europe PMC record states no data deposition; registry enrichment: code_url=null, data_source=null, data_accession=null). All reported quantitative results are Western-blot densitometry and RAS-GTP enrichment ratios, reproducible only by repeating the wet-lab experiments - outside the pipeline-derived scope. Well-founded, honest drop (a text-mining false positive for computational reproduction), not blocked by any our-side failure; «our HPC» was reachable but no compute was applicable. Did NOT attempt the wet-lab signaling experiments. Artifacts: scope.md, original/claims.tsv + publication.md, data/dataset_profile.json, reproduction/agreement.json + environment.lock, AUDIT.md, this ROOM_RESULT.json.
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 assessmentassessed: 2026-06-19 ⛓ 87db2de498a2
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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
- 2026-06-22
- 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 19035362
Title: Oncogenic HRAS mutations cause prolonged PI3K signaling in response to epidermal growth factor in fibroblasts of patients with Costello syndrome. Authors: Rosenberger G, Meien S, Kutsche K. Venue: Human Mutation, 2009 (Mar; 30(3):352-62). PMID 19035362. Code: none (no repository; manifest code_url = null). Data accession: none (no GEO/SRA/ArrayExpress/figshare/zenodo; manifest data_accession = null).
What the paper actually does
A primary-cell wet-lab signal-transduction study. The authors take primary skin fibroblasts from Costello-syndrome (CS) patients carrying germline HRAS gain-of-function mutations and from normal controls, and characterise RAS/PI3K/AKT and RAF-MEK-ERK signalling dynamics in response to EGF.
Experimental techniques (all wet-lab):
- Primary human skin-fibroblast culture (patient + control lines)
- Active-RAS (GTP-bound HRAS) pulldown / RAS-GTP assay
- EGF time-course stimulation
- SDS-PAGE + immunoblotting (Western blots) for total + phospho proteins (p-AKT, p-ERK1/2, p-MEK, etc.)
- Densitometric quantification of blot bands
- Pharmacological inhibition (PI3K inhibitors, e.g. LY294002/wortmannin)
Reported quantitative results are densitometry of Western-blot bands and RAS-GTP enrichment ratios — i.e. manual/instrumental wet-lab measurements, not the output of any bioinformatic pipeline.
In-scope (pipeline-derived computational results)
NONE. The paper contains no sequencing, no microarray, no high-throughput omics, no image-analysis pipeline with shipped data, and no deposited dataset or analysis code. There is no computational pipeline whose output can be re-run from public inputs.
Out-of-scope (wet-lab / manual — not attempted)
All reported results:
- RAS-GTP enrichment in CS vs normal fibroblasts (active-RAS pulldown densitometry)
- AKT phosphorylation kinetics (diminished early / enhanced late phase of EGF response)
- ERK/MEK phosphorylation time courses
- PI3K-inhibitor pharmacology effects These derive from cell-culture experiments and blot densitometry. They are reproducible only by repeating the wet-lab work, which is outside this study's scope (pipeline-derived computational results only).
Verdict
DROP — drop_reason = non_pipeline. This is a text-mining/registry false
positive for a computational reproduction: a 2009 wet-lab signalling paper with no
deposited data, no code, and no pipeline output to reproduce. This is a
well-founded drop (healthy=true): the outcome was correctly determined, not blocked
by any our-side failure. No «our HPC» compute was required or run.
No individual results have been recorded for this entry yet.
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.
This is an honest non_pipeline DROP: Rosenberger et al. (Hum Mutat 2009) is a primary-cell wet-lab signal-transduction study (active-RAS pulldown, EGF time-course immunoblotting, PI3K-inhibitor pharmacology) with no deposited data, no accession, and no analysis code. All three headline findings are qualitative Western-blot/densitometry results reproducible only by repeating the bench experiments, so there is nothing in computational scope to regenerate — a text-mining false positive for reproduction. This is on the data-availability/scope axis (q1/q2 red), not a substantive discrepancy or fabrication signal, so the central claim is simply unverifiable (limited) rather than refuted.
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.