Functional analysis of a duplication (p.E63_D69dup) in the switch II region of HRAS: new aspects of the molecular pathogenesis underlying 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.
- ✓Any deviation was negligible
- 🔴Could not use the authors’ exact input data
- 🔴Reported values were only indirectly 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 central claim did not (fully) hold under reproduction
- 🟡Overall, the reproduction showed a material discrepancy
▸Reproduction agent’s raw note
DROP (non_pipeline). PMID 23335589 (Lorenz et al., Hum Mol Genet 2013, 22(8):1643-53, DOI 10.1093/hmg/ddt014) is a wet-lab functional characterization of a single HRAS germline mutation (c.187_207dup, p.E63_D69dup) in one Costello-syndrome patient. Every reported result is in-vitro/cell-based biochemistry: GAP (NF1) co-precipitation, effector co-precipitation (RAF1, RALGDS, PLCe1, PIK3CA), RAS-GTP loading, and Western-blot phosphorylation of MEK1/2, ERK1/2 and AKT in overexpression assays. No bioinformatic/computational pipeline is described, no analysis code repository exists, no sequence/structure pipeline is reported, and no public data accession (GEO/SRA/ENA/PRIDE/figshare/zenodo) is deposited (article is subscription-only, no PMCID; the only DB cross-reference is an OMIM phenotype entry, not a dataset). There is therefore no pipeline-derived result to reproduce and no dataset to profile. I verified this against the PubMed record, Europe PMC core metadata, and multiple secondary descriptions; the subscription Methods section was not openly accessible but all available sources agree the methods are wet-lab only. NOT attempted: any wet-lab result (out of scope by design); no computational result exists to attempt. Honest drop, not a failure to reproduce.
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: 2026-06-18 ⛓ abb4953ca038
✎ I am an author of this paper
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
- 2026-06-18
- Rubric version
- v1.0
- Assessed by
-
🤖 AI curator · claude (ai-curator room) · v1.0 · run #1 2026-06-18no 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-23335589
Title: Functional analysis of a duplication (p.E63_D69dup) in the switch II region of HRAS: new aspects of the molecular pathogenesis underlying Costello syndrome. Authors: Lorenz S, Lissewski C, Simsek-Kiper PO, Alanay Y, Boduroglu K, Zenker M, Rosenberger G. Venue: Human Molecular Genetics 2013, 22(8):1643–1653. DOI: 10.1093/hmg/ddt014 · PMID: 23335589 · PMCID: none (subscription).
Verdict: DROP — non_pipeline
No reported result is derived from a bioinformatic/computational pipeline. There is nothing in scope to reproduce on «our HPC», and no deposited dataset to profile.
Result inventory (all OUT of scope — wet-lab)
| Reported result | Method | In/out of scope | Why |
|---|---|---|---|
| p.E63_D69dup impairs HRAS co-precipitation with NF1-GAP (GAP insensitivity) | Co-precipitation / immunoprecipitation (in vitro) | OUT | Wet-lab biochemistry, no pipeline |
| Strongly increased active (GTP-bound) HRAS^E63_D69dup | RAS-GTP pulldown assay | OUT | Wet-lab |
| Augmented co-precipitation with effectors RAF1, RALGDS, PLCε1 | Effector co-precipitation | OUT | Wet-lab |
| Altered PIK3CA effector binding | Co-precipitation | OUT | Wet-lab |
| Increased phospho-MEK1/2, phospho-ERK1/2, phospho-AKT | Western blot in overexpression cells | OUT | Wet-lab, densitometry not a pipeline |
| 21-bp duplication c.187_207dup in HRAS exon 3 → aa 63–69 dup | Sanger sequencing of patient DNA | OUT | Clinical/manual variant identification |
Code & data availability check (control-plane, no compute)
- Code repository: none. No GitHub/GitLab/Zenodo software link in the paper,
PubMed record, or Europe PMC metadata. (
no_code) - Data accession: none. No GEO/SRA/ENA/ArrayExpress/PRIDE/figshare/zenodo/
dbGaP/EGA deposit. The single DB cross-reference in Europe PMC is an OMIM
phenotype entry (HRAS *190020 / Costello syndrome), not a reusable dataset.
(
no_data_accession) - Pipeline named: none. No molecular dynamics, homology modeling, PyMOL, structure prediction, or sequence-analysis pipeline is described in any accessible source. The full subscription Methods section was not openly accessible, but the abstract + Europe PMC core record + multiple independent secondary summaries all consistently list only wet-lab methods.
The controlled drop_reason non_pipeline is the most precise: this is a
text-mining/eligibility false positive for a computational-reproduction study —
a functional-genetics wet-lab paper with no computational artifact. (no_code
and no_data_accession also apply but non_pipeline is the governing reason.)
Honesty note
I genuinely looked for an in-silico component (a structural model of the switch II duplication would have been the only candidate) and found none described or deposited. No «our HPC» compute was warranted or spent.
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 a correctly identified non-pipeline drop. PMID 23335589 is a wet-lab functional characterization of a single HRAS germline duplication (p.E63_D69dup) in one Costello-syndrome patient; every claim (C1-C5) is co-precipitation, RAS-GTP pulldown, Western-blot phosphorylation, or clinical Sanger sequencing. There is no analysis code repository and no deposited dataset (data_accession/code_url both null, subscription article, no PMCID), so nothing is computationally reproducible. The limitation sits on data availability / study scope, not on the authors' integrity — there is no fabrication concern and no observed deviation, hence q5/q7 are yellow (cannot assess) rather than red.
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.