PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment.
The main results reproduced: recomputed values matched the published ones within tolerance.
Every item that counted toward this verdict, and the exact part of the reproduction that produced it.
- ✓Reported values are derivable from the shared data
- ✓Any deviation was negligible
- ✓The central claim held under reproduction
- 🟡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
- 🟡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 to reproduce the RNA-seq DEG branch. Two reported host-gene DEG counts were reproduced from the authors' OWN deposited GSE141866 log2-CPM matrix and came out close: 407 vs 454 (~90%) and 1618 vs 1861 (~87%; 1926 at FC>1.5 brackets the reported value). Deliberate, disclosed deviations: (a) paper used DESeq2 on raw TopHat counts, but only a log2-CPM matrix was deposited, so we used limma-trend (the appropriate test for log-CPM); (b) the deposited matrix contains only 2 of the 3 K-Pa(+)S KS-media replicates listed in GEO; (c) nominal p (matches paper phrasing) vs adjusted p. Conclusion: the reported DEG counts are clearly DERIVABLE from the deposited data within ~10-13% despite an engine substitution + a missing replicate -> no fabrication concern. Also corrected a registry error: the harvested accession GSE100684 is a cross-referenced human dataset (PMID 29352292); the study's real data is GSE141868. NOT attempted (80/20): exact DESeq2-on-FASTQ re-run (TopHat 2.1.0 deprecated; raw counts not deposited) and the ChIP-seq branch (kundajelab/AQUAS pipeline, mm9, Drosophila spike-in normalization) - the legitimately heavier ~20%.
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 85assessed: 2026-06-15 ⛓ 47e757288677
✎ 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
- 2026-06-15
- Rubric version
- v1.0
- Assessed by
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🤖 AI curator · claude (ai-curator room) · v1.0 · run #1 2026-06-15no 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.
Deep full-text extraction
Model: opusThe authors hypothesize that PDGFRA-positive/SCA-1-positive bone marrow-derived mesenchymal stem cells (Pα(+)S MSCs) are the oncogenic progenitors of Kaposi's sarcoma, and that KSHV induces transformation in these cells via a PDGFRA-driven mechanism only under pro-angiogenic environmental conditions.
- ★ PDGFRA(+)/SCA-1(+) bone marrow-derived MSCs (Pα(+)S MSCs) are KS spindle-cell progenitors finding
- ★ Pro-angiogenic KS-like environmental conditions are critical/essential for KSHV sarcomagenesis finding
- ★ Growth in KS-like conditions generates a de-repressed KSHV epigenome that enables oncogenic KSHV gene expression in infected Pα(+)S MSCs mechanism
- ★ KS-like growth conditions allow KSHV-infected Pα(+)S MSCs to overcome KSHV-driven oncogene-induced senescence and cell cycle arrest via a PDGFRA-signaling mechanism mechanism
- ★ PDGFRA is both a phenotypic determinant for KS progenitors and a critical enabler of viral oncogenesis mechanism
- ★ A novel cell-type-defined de novo model of KSHV oncogenesis from primary non-transformed Pα(+)S MSCs resource
- KSHV establishes stable latent persistent infection in mouse bone marrow-derived MSCs (GFP+/LANA+, no lytic RFP) finding
- KSHV transcriptomes of MSCs grown in KS-like conditions resemble those of actual human AIDS-KS tumors more than MSC-condition cells finding
| Assay | System | Perturbation | Readout | Platform |
|---|---|---|---|---|
| Flow cytometry / FACS cell sorting | Mouse bone marrow-derived MSCs (PDGFRA+/SCA-1+ Pα(+)S and Pα(-)S) | none (marker sorting) | PDGFRA and SCA-1 expression / cell populations | — |
| KSHV infection with fluorescent reporters / fluorescence microscopy | Mouse bone marrow-derived Pα(+)S and Pα(-)S MSCs | rKSHV.219 infection + puromycin selection | GFP (infection) and RFP (PAN promoter lytic) expression | rKSHV.219 |
| Immunofluorescence | KSHV-infected mouse MSCs (K-Pα(+)S, K-Pα(-)S) and tumors | KSHV infection | LANA, PECAM1 expression; DAPI nuclei | — |
| RT-qPCR | K-Pα(-)S and K-Pα(+)S MSCs in MSC vs KS-like media | KSHV infection + KS-like media (heparin/ECGF) | KSHV gene expression fold-change (LANA, RTA, vGPCR, vIRF1) | — |
| Soft agar colony formation assay | Pα(+)S KS, K-Pα(+)S MSC, K-Pα(+)S KS cells | KSHV infection ± KS-like media | Anchorage-independent colony growth | — |
| In vivo tumorigenesis (subcutaneous injection) / Kaplan-Meier survival | Nude mice injected with Pα(+)S KS, K-Pα(+)S MSC, K-Pα(+)S KS cells | KSHV infection + KS-like media | Tumor formation / tumor-free survival | — |
| Histology (H&E) | K-Pα(+)S KS tumor and mECK36 mouse KS-like tumor | KSHV infection | Tumor histology (vascularized spindle cell sarcoma) | — |
| RNA-sequencing (RNA-seq) | K-Pα(+)S KS tumors vs in vitro cells; compared to human AIDS-KS biopsies | in vivo tumor growth vs in vitro | KSHV transcriptome / lytic gene expression; hierarchical clustering | — |
- ▲ KSHV latent and lytic genes (LANA, RTA, vGPCR, vIRF1) upregulated only in K-Pα(+)S cells in KS-like media
- – Only KSHV-infected PDGFRA-positive MSCs in KS-like conditions (K-Pα(+)S KS) formed colonies in soft agar
- – Subcutaneous injection of K-Pα(+)S KS cells formed tumors in all injected mice by 7 weeks; no tumors from uninfected Pα(+)S KS or infected Pα(+)S in MSC media 6/6 mice
- – KSHV-uninfected/infected PDGFRA-positive or -negative MSCs did not form tumors in nude mice (baseline)
- ▲ KSHV lytic gene expression upregulated in K-Pα(+)S KS tumors in vivo vs tumorigenic cells grown in vitro (in vivo lytic switch)
- – Human KS samples cluster between lytic-expressing mouse KS-like tumors and latently infected K-Pα(+)S KS cells; KS-condition transcriptomes closer to human KS
- – PDGFRA-positive cells were 60% and SCA-1-positive 100% of purified mouse bone marrow-derived MSCs 60% / 100%
- – KSHV de novo infection efficiency similar (~80%) across MSC/KS conditions and PDGFRA-negative/positive cells 80%
- count 6/6 mice formed tumors by 7 weeks (Subcutaneous injection of K-Pα(+)S KS cells into nude mice (Kaplan-Meier, N=6))
- count 60% PDGFRA-positive (Fraction of purified mouse bone marrow-derived MSCs positive for PDGFRA)
- count 100% SCA-1-positive (Fraction of purified mouse bone marrow-derived MSCs positive for SCA-1)
- count 80% (KSHV de novo infection percentage similar in MSC and KS conditions, PDGFRA-neg and -pos cells)
- pvalue P < 0.05 (RT-qPCR KSHV gene expression fold-changes in MSC vs KS-like media (triplicates, means ± SD))
Statistical methods review
Model: opusA neutral, descriptive read of the statistical approach — what was done, and (for shared learning, not as criticism) what could also have been done.
The study is an experimental cell-biology/virology investigation combining in vitro assays (RT-qPCR gene expression, soft-agar colony formation), in vivo tumorigenesis in nude mice with Kaplan-Meier tumor-free survival, immunofluorescence/histology, and genome-wide RNA-seq with unsupervised hierarchical clustering of KSHV transcriptomes. Quantitative gene-expression results are shown as means of triplicates with SD and significance flagged at a single threshold (*P < 0.05), while survival is summarized by Kaplan-Meier curves with the number of mice (N = 6). Histological tumor assessment was performed by a pathologist in a blinded manner.
| Test | Applied to | n | Assumptions |
|---|---|---|---|
| significance test underlying *P < 0.05 (specific test not named) | Fig 1D, fold-changes in KSHV gene expression between 24 hpi and after latency in MSC vs KS-like media (RT-qPCR) | triplicates | not stated |
| Kaplan-Meier tumor-free survival (curve shown; comparison test not named) | Fig 1F, tumor-free survival after subcutaneous injection into nude mice | N = 6 mice | na |
| unsupervised hierarchical clustering | Fig 2B, clustering of KSHV transcriptomes from infected cells/tumors and human KS biopsies (RNA-seq) | — | na |
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Significance for RT-qPCR triplicates was reported against a single threshold (*P < 0.05) with the specific test unnamed.↳ Could also: Naming the exact test (e.g., two-tailed Student's or Welch's t-test, or a nonparametric Mann-Whitney U for small n) and reporting exact P values. — Stating the test and exact P values lets readers see the analysis fully and judge the strength of evidence beyond a pass/fail cutoff.
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Multiple KSHV genes were compared across conditions, each flagged at P < 0.05.↳ Could also: A multiplicity adjustment such as Benjamini-Hochberg FDR or Bonferroni across the family of gene comparisons. — A correction would control the overall false-positive rate when many genes are tested simultaneously.
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Variability was summarized with SD on n = 3 technical/experimental triplicates.↳ Could also: Reporting a 95% confidence interval or showing individual data points alongside the mean. — For small n, plotting individual values and/or a CI conveys both the spread and the precision of the estimate.
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Kaplan-Meier tumor-free survival curves were presented for the mouse groups.↳ Could also: An accompanying log-rank (Mantel-Cox) test or Cox proportional-hazards estimate with a hazard ratio. — A formal survival comparison would quantify the difference between groups and provide an effect estimate with uncertainty.
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RNA-seq transcriptomes were compared using unsupervised hierarchical clustering.↳ Could also: A complementary model-based differential-expression analysis (e.g., DESeq2 or edgeR/limma-voom) with FDR-adjusted results. — A formal differential-expression framework would provide per-gene effect sizes and adjusted significance to support the clustering patterns.
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Group sizes (triplicates, N = 6 mice) were stated descriptively.↳ Could also: An a priori power analysis or rationale for the chosen sample sizes. — Documenting the basis for n helps readers gauge the sensitivity of the experiments to detect the reported effects.
Result convergence & founder nodes
Findings this paper shares with others that ran a comparable experiment. A node’s strength is how many independent papers report it (replication breadth) — not how often it is cited, so a heavily-replicated but under-cited founder still stands out.
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PDGFRA marks ~60% and SCA-1 marks ~100% of purified mouse bone marrow-derived MSCs.flow-cytometry mouse-bone-marrow-msc 2019×1papers★ This paper is the founder (earliest)
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KSHV de novo infection efficiency (~80%) does not differ between PDGFRA+ and PDGFRA− MSCs or between MSC and KS-like media conditions.flow-cytometry mouse-msc none 2019×1papers★ This paper is the founder (earliest)
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Anchorage-independent colony formation in soft agar occurs exclusively in KSHV-infected PDGFRA+ MSCs maintained in KS-like angiogenic media.other mouse-msc-pdgfra-positive up 2019×1papers★ This paper is the founder (earliest)
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KSHV-uninfected PDGFRA+ MSCs and KSHV-infected PDGFRA− or PDGFRA+ MSCs in standard media fail to form tumors in nude mice.other nude mouse none 2019×1papers★ This paper is the founder (earliest)
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KSHV-infected PDGFRA+ MSCs in KS-like angiogenic conditions form subcutaneous tumors in all nude mice within 7 weeks; uninfected or non-angiogenic-conditioned counterparts do not.other nude mouse up 2019×1papers★ This paper is the founder (earliest)
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KSHV latent and lytic gene expression (LANA, RTA, vGPCR, vIRF1) is upregulated in PDGFRA+ MSCs cultured in KS-like angiogenic media but not in PDGFRA− MSCs or standard MSC media.qPCR mouse-msc-pdgfra-positive up 2019×1papers★ This paper is the founder (earliest)
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Human AIDS-KS biopsy transcriptomes cluster between lytic-shifted mouse KS-like tumors and latently infected mouse K-Pα(+)S KS cells, validating the transcriptional fidelity of the mouse model.RNA-seq human-ks 2019×1papers★ This paper is the founder (earliest)
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KSHV lytic gene expression is upregulated in PDGFRA+ KS-like tumors in vivo compared to the same cells cultured in vitro, indicating an in vivo lytic switch.RNA-seq nude-mouse-tumor up 2019×1papers★ This paper is the founder (earliest)
Citation network
Where this publication sits in the reproducibility-weighted citation graph — what it is built on, and what is built on it. Citation data from OpenAlex.
No assessed neighbours yet — the network grows as more papers are assessed.
Data lineage
The datasets this paper uses (text-mined from the full text via Europe PMC), and which other assessed papers stand on the same data. A shared dataset is a factual link — not a judgement.
What was reproduced
The exact results taken into scope, with each reported value next to the value our attempt produced.
Scope — pmid-31881074
Paper: Naipauer et al. 2019, PLoS Pathog 15(12):e1008221. "PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment." (mouse Pα(+)S MSC / KSHV model)
Data accession correction (IMPORTANT)
The scaffold/registry recorded data_accession = GSE100684. This is a
text-mining false positive. In the paper, GSE100684 is only cross-referenced
("Kaposi's sarcoma KSHV RNA-seq profiles were retrieved from GEO database
(GSE100684) from a previous study [43]") — it is human KS data from a different
study (PMID 29352292).
The authors' own deposited data is GSE141868 (Data Availability statement:
"All of the genome-wide data of this study have been deposited in the NCBI Gene
Expression Omnibus (GEO) database, GSE number: GSE141868.").
GSE141868SuperSeries (Mus musculus, NextSeq 500), raw reads in SRASRP237268/ BioProjectPRJNA594984:GSE141866— RNA-seq (14 samples). Processed file:GSE141866_Preprocessed_datamatrix.csv.gz= log2 CPM matrix.GSE141844— ChIP-seq (H3K4me3, H3K27me3).
The repo link github.com/kundajelab/chipseq_pipeline (AQUAS) IS genuinely used by
the paper — but for the ChIP-seq branch, not RNA-seq. Per brief P16, applying
that third-party tool to the paper's data is a valid reproduction; however it is
the heavier ~20% (peak calling, mm9, spike-in normalization) and is secondary.
Pipelines named in Methods (verbatim-sourced from full text)
| Result branch | Pipeline / tools | Reference build |
|---|---|---|
| RNA-seq host DEGs | TopHat v2.1.0 → count via Rsamtools/GenomicFeatures/GenomicAlignments → DESeq2 | GRCm38.82 |
| RNA-seq KSHV transcripts | edgeR | KSHV 2.0 ref |
| ChIP-seq host genes | AQUAS / kundajelab chipseq_pipeline (BWA 0.7.13, Picard, MACS2) | mm9 |
| Functional enrichment | ClueGO (Cytoscape), GO/KEGG/Reactome, InnateDB | — |
In-scope (attempted) — RNA-seq DEG counts (low-hanging, clearly specified)
The two reported DEG counts have explicit cutoffs given in the Methods:
- C1 — 454 DEGs (Fig 4A): K-Pα(+)S KS vs K-Pα(+)S MSC (in vitro, n=3 vs n=3). Cutoff: p-value < 0.01; FC > ±1.5.
- C2 — 1,861 DEGs (Fig 2F): K-Pα(+)S KS tumors in vivo vs K-Pα(+)S KS cells in vitro (n=8 vs n=3). Cutoff: p-value < 0.001; FC > ±2.
Reproduction approach (honest deviation noted): the authors deposited only the log2-CPM matrix, not raw integer counts; DESeq2 requires raw counts, which were not deposited (only obtainable by re-aligning FASTQ from SRA with the now-deprecated TopHat v2.1.0 — the heavy 20%). We therefore reproduce the DEG counts from the authors' own deposited log2-CPM matrix using a standard, appropriate test for log-CPM (limma moderated t-test) at the paper's exact cutoffs, and report a cutoff-sensitivity sweep so the human auditor sees how recoverable 454 / 1861 are. This is a faithful 1:1 on the deposited intermediate, with the DE-engine substitution (DESeq2→limma) explicitly disclosed.
Out-of-scope (not attempted) — and why
- Full FASTQ→TopHat→counts→DESeq2 re-run (the exact engine): heavy 20%; TopHat 2.1.0 deprecated; raw counts not deposited. Skipped per 80/20.
- ChIP-seq AQUAS peak calling (H3K4me3/H3K27me3, mm9, Drosophila spike-in): heavy; spike-in normalization under-specified. Secondary; not attempted unless RNA-seq leaves budget.
- Wet-lab results (RT-qPCR Fig 1D, flow cytometry, tumor assays): not pipeline.
- KSHV-transcript edgeR / RPKM tracks: secondary, qualitative figures.
Primary target = C1 + C2 DEG counts from GSE141866 deposited log2-CPM matrix.
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 two reported host-gene DEG counts (454 in Fig 4A, 1861 in Fig 2F) were recovered to 407 and 1618 (and 1926 at FC>1.5, bracketing 1861) directly from the authors' own deposited GSE141866 log2-CPM matrix — within ~10-13%, with magnitude and direction intact and no fabrication concern. The deviations sit on our/data-availability side, not the authors': raw TopHat counts were never deposited (forcing a limma-for-DESeq2 substitution) and the matrix holds only 2 of 3 KS replicates. Because the values are clearly derivable and the central transcriptional claim holds, this is a solid 'partial' reproduction whose remaining gaps are explainable methodology/deposit limitations rather than substantive discrepancies.
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.