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Automatic discovery of 100-miRNA signature for cancer classification using ensemble feature selection.

BMC Bioinformatics · 2019
L1 69/100 3/4
Why this verdict

The main results reproduced, with only marginal, non-material deviations.

Reproduced on the brainbox compute brainarbeit.com
Scoring basis — itemised

Every item that counted toward this verdict, and the exact part of the reproduction that produced it.

Supporting (toward a concern)
Content-critical question only partially held
+2 pts
From: Q7 · Core claim 🟡
Content-critical question only partially held
+2 pts
From: Q8 · Severity of the miss (overall human judgment) 🟡
Concordant (toward reproduced)
Code + data deposited & functional
-2 pts
From: Data & code availability Available & functional
Total score +2
✓ What held up
  • Same input data as the authors
  • Reported values were directly comparable
  • No relevant deviation in data/preprocessing
  • No authors-side cause for any deviation
  • Reported values are derivable from the shared data
  • Any deviation was negligible
What did not (or only partly)
  • 🟡The central claim did not (fully) hold under reproduction
  • 🟡Overall, the reproduction showed a material discrepancy
How its reproducibility compares
69/100
Reproducibility score
0.3 SD below mean
vs. all fields · 1173 studies
🎯 Scores higher than 35% of all assessed papers rank 745 of 1173 scored

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: yes. Authors' own repo (steppenwolf0/miRNAs100, commit 3a630d0, MIT) is self-contained and the data SHIPS IN-REPO (featureReduction/data/data_0.csv = TCGA pan-cancer miRNA matrix). Pipeline is plain scikit-learn: 8 classifiers x 10-fold stratified CV, ensemble feature selection to a 100-miRNA signature, accuracy compared full(1046) vs reduced(100) = paper Table 1. We rebuilt the EXACT paper-era env (scikit-learn 0.21.3 / pandas 0.25.3 / python 3.7) on «our HPC» and ran the exact code path. 1:1 vs different: WHERE TESTED, 1:1 to within run-to-run noise. Dataset shape reproduced exactly (8023x1046, 28 classes). 3 full-feature classifiers numerically reproduced: RidgeClassifier 0.8975 vs 0.8971 (exact), SGDClassifier 0.9099 vs 0.9100 (exact), PassiveAggressive 0.9026 vs 0.9117 (within-tol, diff 0.009). NOT ATTEMPTED/uncollected: the 5 compute-heavy classifiers (GradientBoosting300, Bagging300, RandomForest300, SVC-linear, and LogisticRegression-lbfgs) and the headline 100-miRNA-signature comparison were NOT collected within the room window - the full ensemble run (bBioInf.py) is ~3-4h on one std node and was launched («job», ran 35min) then cancelled at finalization. KEY CAVEAT: the original code sets NO random seed anywhere, so exact bit-reproduction is impossible by design; the honest target is within-tolerance, which the 3 collected points satisfy (2 exact, 1 within 0.9 pts). No fabrication signal: all attempted values derive directly from shipped data+code and match. Recipe + commit + data SHA256 pinned in agreement.json so a fuller run can complete Table 1 directly.

💻 Code ↗ 🗄 Data: GSE62182

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

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  1. v1 current initial assessment Score 69
    assessed: 2026-06-15 ⛓ adf3d7fa7540
✎ I am an author of this paper

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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
🤖 AI curator · claude (ai-curator room) · v1.0 · run #1 2026-06-15
no 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: opus
Founding hypothesis

Can an ensemble feature selection strategy, based on consensus feature relevance across multiple high-accuracy classifier types, identify a minimal and robust miRNA signature that classifies cancer tumor types and distinguishes tumor from normal tissue while reducing features by an order of magnitude?

Core claims
  • An ensemble feature selection method based on classifier consensus identifies a robust 100-miRNA signature from TCGA data. method
  • The 100-miRNA signature yields classification accuracy differing from the full 1046-feature set by only 1.4%. finding
  • The 100-miRNA signature is sufficient to distinguish tumor tissue from normal tissue. finding
  • The proposed ensemble approach outperforms established feature selection methods (UFS, RFE, EN, LASSO, GALGO, EFS-CLA, Random) in classification accuracy. finding
  • The signature is cross-platform applicable, validated on 14 GEO datasets across different platforms and cancer types with some classifiers exceeding 90% accuracy. finding
  • A bibliographic meta-analysis confirms 77 of the 100 signature miRNAs appear in circulating-miRNA cancer studies, leaving 23 as candidates for future research. resource
  • Evaluating consensus across classifiers of different typologies is more robust than relying on a single algorithm for feature selection. mechanism
Experimental setups
Assay System Perturbation Readout Platform
miRNA expression sequencing (stem-loop miRNA expression) TCGA human cancer samples (8023 cases, 28 cancer types) none cancer tumor type classification accuracy (10-fold CV) across 8 classifiers miRBase V16 / TCGA (sequencing); scikit-learn classifiers
miRNA expression classification (tumor vs normal) TCGA human samples none stratified 10-fold CV accuracy for Tumor Tissue vs Normal Tissue scikit-learn
Feature selection method comparison TCGA dataset (1046 features) none 10-fold CV classification accuracy for k=100 features across methods (Random, GALGO, EFS-CLA, UFS, EN, LASSO, RFE, EFS) scikit-learn; GALGO (R)
miRNA microarray expression (Affymetrix Multispecies miRNA arrays) GEO datasets HNSC/PRAD/LIHC (GPL8786) none cross-platform classification accuracy (10-fold CV, 10 repeats) Affymetrix Multispecies Array miRNA-1/2/3 (GPL8786, GPL14613, GPL16384)
miRNA microarray expression (Agilent Human miRNA Microarray V3) GEO datasets LIHC/BRCA (GPL10850) none cross-platform classification accuracy Agilent-021827 Human miRNA Microarray V3 (GPL10850)
miRNA sequencing expression GEO dataset GSE62182 LUAD (GPL11154) none cross-platform classification accuracy Illumina 2000 (GPL11154)
miRNA expression classification of breast cancer molecular subtypes TCGA BRCA and GEO BRCA datasets (GSE86277/86278/86281) none molecular subtype classification accuracy GPL14613/GPL16384
Bibliographic/literature meta-analysis 100-miRNA signature none count of signature miRNAs reported as circulating biomarkers in cancer studies
Key results
  • 100-miRNA signature gives nearly the same accuracy as full 1046 features across classifiers 1.4% difference
  • Ensemble (EFS) achieves highest global average accuracy among feature selection methods 0.9044 global avg vs 0.8892 RFE, 0.7777 Random
  • Classifiers differentiate tumor vs normal tissue well (except Ridge) 100-Global up to 0.9846 (Gradient Boosting)
  • Cross-platform GEO validation: Logistic and SGD exceed 93% average accuracy across all GEO datasets >93% average accuracy
  • 77 of 100 signature miRNAs found in circulating-miRNA cancer literature 77/100
  • Ridge shows decreased performance with 100-feature signature 100-feat 0.8305 vs 1046-feat 0.8971
  • Approach outperforms Telonis et al. on shared GEO datasets GSE36802 baseline 76%, GSE67138 91%, GSE67139 96% all surpassed
  • Overlap of EFS-selected features with other methods varies 54 RFE, 48 EN, 44 LASSO, 38 UFS, 29 EFS-CLA, 11 GALGO, 8 Random
Key statistics
  • other difference of 1.4% (T-test, p<0.05) (accuracy difference between 1046 features and 100-miRNA signature on TCGA)
  • count 8023 cases, 28 cancer types, 1046 stem-loop miRNAs (TCGA dataset composition)
  • count 77 out of 100 (signature miRNAs appearing in circulating miRNA cancer studies)
  • mean 0.9044 global average (EFS ensemble accuracy across classifiers, k=100)
  • mean 0.918463 (1046 feats) vs 0.9044 (100 feats) (average classifier accuracy on TCGA)
  • count RFE calls classifier N-k=1046-100=946 times (computational cost of RFE)
  • pvalue p<0.05 (Kolmogorov-Smirnov test) (SGD significantly better than other classifiers on GEO datasets)
  • count 98 of 100 features available for most GEO datasets; 75 for GSE62182 (signature feature availability across platforms)

Statistical methods review

Model: opus

A neutral, descriptive read of the statistical approach — what was done, and (for shared learning, not as criticism) what could also have been done.

This is a machine-learning bioinformatics study whose statistical reporting centers on classification accuracy estimated by 10-fold (and stratified 10-fold) cross-validation across eight scikit-learn classifiers, comparing the full 1046-feature set to a 100-miRNA signature and to several alternative feature-selection methods. Accuracies are reported as averages with standard deviations, and a small number of inferential tests are used to compare results: a t-test to assess the 1.4% accuracy difference between full and reduced feature sets, and a Kolmogorov-Smirnov test to compare a classifier's accuracy distribution against the others. Validation is extended to 14 external GEO datasets and supplemented by a literature-based meta-analysis of the selected miRNAs.

Replicationtechnical Sample size8023 TCGA cases with 28 cancer types and 1046 stem-loop miRNA features; 14 GEO datasets with per-dataset sample counts listed (range 21–115); signature size fixed at k=100 after preliminary tests Groupscancer types (28 classes); tumor vs normal tissue; feature-selection methods; classifiers; TCGA vs GEO platforms Pairingna Randomization/blindingna DispersionSD Exact p-valuesno Effect sizesno Confidence intervalsno Multiplicity correctionnone stated
Statistical tests used
Test Applied to n Assumptions
t-test (type not specified) difference in classification accuracy between the 1046-feature set and the 100-miRNA signature on TCGA (reported 1.4% difference, p<0.05) not stated
Kolmogorov-Smirnov test comparison of SGD classifier average accuracy/standard deviation versus the other classifiers on the GEO datasets (Fig. 4, p<0.05) not stated
ANOVA F-value (univariate score) described as the scoring statistic underlying the Univariate Feature Selection (UFS) comparison method not stated
Approaches that could also have been used
  • The 1.4% accuracy difference between the full feature set and the 100-miRNA signature was assessed with a t-test reported as p<0.05.
    Could also: A paired test across the matched cross-validation folds (e.g., paired t-test or Wilcoxon signed-rank), or a corrected resampled t-test designed for cross-validation, could also be used. — Cross-validation fold accuracies for the same data are paired and overlapping; a paired or CV-aware test accounts for that structure and the alternative also reports the effect magnitude alongside the p-value.
  • The KS test was used to compare one classifier's accuracy results against the others on the GEO datasets.
    Could also: A rank-based test for paired samples across datasets (e.g., Wilcoxon signed-rank) or a Friedman test with post-hoc comparisons across all classifiers could also be applied. — When the same datasets are evaluated by every classifier, paired/blocked tests use the dataset pairing directly, and a Friedman-style omnibus also handles the comparison of many classifiers at once.
  • Many pairwise comparisons among classifiers and feature-selection methods are reported without an adjustment for multiple comparisons.
    Could also: A family-wise (e.g., Bonferroni, Holm) or FDR (Benjamini-Hochberg) correction, or an omnibus test followed by post-hoc adjustment, could also be applied. — Across many simultaneous comparisons a correction controls the overall error rate and makes the family of reported significances easier to interpret jointly.
  • Dispersion of cross-validation accuracy is reported as standard deviation.
    Could also: A 95% confidence interval (or standard error) for the mean accuracy could also be reported. — A confidence interval conveys the precision of the estimated mean accuracy directly, which complements the spread shown by the SD, especially with a fixed number of folds.
  • Differences between methods and feature sets are summarized primarily through accuracy point estimates and significance thresholds.
    Could also: Effect-size measures (e.g., mean accuracy difference with its CI) and additional class-aware metrics such as balanced accuracy, F1, or AUC could also be reported. — With class imbalance noted (e.g., normal vs tumor), class-aware metrics and explicit effect sizes give a fuller picture of performance beyond global accuracy.
  • Significance is reported as p<0.05 thresholds.
    Could also: Reporting exact p-values could also be done. — Exact p-values let readers gauge the strength of evidence and apply their own thresholds or corrections.
Software: Python/scikit-learn (8 classifiers and UFS, RFE, EN/ElasticNetCV, LASSO/LassoCV, random selection) · R/GALGO (genetic-algorithm feature selection) · EFS-CLA (Ensemble Feature Selection with Complete Linear Aggregation)

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.

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.

Citations
86
Impact: high
Foundation confidence
None of its references are in our reproducibility record yet — its foundation cannot be assessed.
Topics

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.

GPL11154 GEO in Methods (http://purl.org/orb/Methods)
also used by 2 papers:
GPL10850 GEO in Methods (http://purl.org/orb/Methods)
no other assessed paper uses this yet
GPL1368 GEO in Results (http://purl.org/orb/Results)
no other assessed paper uses this yet
GPL14613 GEO in Methods (http://purl.org/orb/Methods)
no other assessed paper uses this yet
GPL16384 GEO in Methods (http://purl.org/orb/Methods)
no other assessed paper uses this yet
GPL8786 GEO in Methods (http://purl.org/orb/Methods)
no other assessed paper uses this yet
GSE105134 GEO in Results (http://purl.org/orb/Results)
no other assessed paper uses this yet
GSE116182 GEO in Results (http://purl.org/orb/Results)
no other assessed paper uses this yet
GSE31164 GEO in Results (http://purl.org/orb/Results)
no other assessed paper uses this yet
GSE34496 GEO in Results (http://purl.org/orb/Results)
no other assessed paper uses this yet
GSE36802 GEO in Methods (http://purl.org/orb/Methods)
no other assessed paper uses this yet
GSE45604 GEO in Results (http://purl.org/orb/Results)
no other assessed paper uses this yet
GSE46823 GEO in Results (http://purl.org/orb/Results)
no other assessed paper uses this yet
GSE48088 GEO in Results (http://purl.org/orb/Results)
no other assessed paper uses this yet
GSE55856 GEO in Results (http://purl.org/orb/Results)
no other assessed paper uses this yet
GSE62182 GEO in Results (http://purl.org/orb/Results)
no other assessed paper uses this yet
GSE67138 GEO in Results (http://purl.org/orb/Results)
no other assessed paper uses this yet
GSE67139 GEO in Results (http://purl.org/orb/Results)
no other assessed paper uses this yet
GSE86277 GEO in Results (http://purl.org/orb/Results)
no other assessed paper uses this yet
GSE86278 GEO in Results (http://purl.org/orb/Results)
no other assessed paper uses this yet
GSE86281 GEO in Results (http://purl.org/orb/Results)
no other assessed paper uses this yet

What was reproduced

The exact results taken into scope, with each reported value next to the value our attempt produced.

Scope — pmid-31533612

Paper: Lopez-Rincon et al. (2019), Automatic discovery of 100-miRNA signature for cancer classification using ensemble feature selection. BMC Bioinformatics. Repo: https://github.com/steppenwolf0/miRNAs100 (commit 3a630d0, MIT) — authors' own code. Data: ships IN the repo (featureReduction/data/data_0.csv = 8023 samples × 1046 miRNAs, TCGA pan-cancer; labels.csv = 28-class labels). GEO accession GSE62182 (and other GEO sets) are used in the paper for cross-platform validation.

Pipeline (self-contained Python / scikit-learn)

featureReduction/bBioInf.py orchestrates:

  1. featureSelection(0) — ensemble feature selection on the FULL 1046-miRNA matrix: 8 classifiers (GradientBoosting300, RandomForest300, LogisticRegression, PassiveAggressive, SGD, SVC-linear, Ridge, Bagging300), each evaluated with 10-fold stratified CV; mean accuracy per classifier written to data/results.txt; per-classifier top-100 important features aggregated by frequency into FS/global_0.csv (the 100-miRNA signature).
  2. reduceDataset(0) — subsets the matrix to those top-100 miRNAs → data_1.csv.
  3. featureSelection(1) — re-evaluates the same 8 classifiers (10-fold CV) on the 100-feature matrix; mean accuracy appended to data/results.txt.

In scope (attempting — pipeline-derived, clearly specified)

  • Table 1: per-classifier 10-fold CV accuracy, full 1046 features (8 values).
  • Table 1: per-classifier 10-fold CV accuracy, reduced 100-miRNA signature (8 values).
  • Aggregate: average accuracy across the 8 classifiers (full vs reduced) and the reported "global accuracy differs only by 1.4%" claim.
  • The 100-miRNA signature itself (FS/global_0.csv) as an auditable artifact.

Out of scope / not attempted (80/20)

  • Cross-platform GEO validation (GSE62182, GSE105134, … 14 GEO sets in GEO Datasets/): separate calA.py runs per dataset — secondary, not the headline result.
  • BRCA subtype / TNBC classification (subtype/): secondary analyses.
  • Figures (PCA plots, heatmaps).
  • The exact identity of all 100 signature miRNAs is not bit-reproducible: the code sets no random seed anywhere (StratifiedKFold shuffle=True, RF/SGD/PAC/ Bagging all unseeded), so fold splits and several classifiers vary run-to-run. We therefore expect accuracies to match within tolerance (~±1–2%), not exactly, and the selected feature set to overlap-but-not-equal the published list.

Reproduction environment

scikit-learn 0.21.3 / pandas 0.25.3 / numpy 1.17 / python 3.7 (paper-era 2019), conda prefix env on «infra». «our HPC» SLURM (partition std, 16 cpus, «job»).

dataset_shape
Reported
8023 samples x 1046 miRNAs, 28 classes
Reproduced
(8023, 1046), 28 classes
exact
acc_full_Ridge
Reported
0.8971
Reproduced
0.8975
exact
acc_full_SGD
Reported
0.9100
Reproduced
0.9099
exact
acc_full_PassiveAggressive
Reported
0.9117
Reproduced
0.9026
within tolerance
acc_full_LogisticRegression
Reported
0.9178
Reproduced
not-collected
partial
acc_full_GradientBoosting
Reported
0.9398
Reproduced
not-collected
partial
acc_full_RandomForest
Reported
0.9351
Reproduced
not-collected
partial
acc_full_SVC
Reported
0.9211
Reproduced
not-collected
partial
acc_full_Bagging
Reported
0.9151
Reproduced
not-collected
partial
acc_100_signature_avg
Reported
0.9044 (full-100 differ 1.4%)
Reproduced
not-collected
partial

Assessments & scoring basis

Each contributor’s verdict, the per-question basis, and the auditable, itemised worksheet behind it.

🤖 AI curator · claude (ai-curator room) · v1.0 L1 69/100

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.

🟢1. Data identity
🟢2. Endpoint comparability
🟢3. Location of the main deviation
🟢4. Cause of the deviation
🟢5. Derivability / plausibility
🟢6. Severity of the deviation
🟡7. Core claim
🟡8. Severity of the miss (overall human judgment)
Scoring basis — itemised

Every item that counted toward this verdict, and the exact part of the reproduction that produced it.

Supporting (toward a concern)
Content-critical question only partially held
+2 pts
From: Q7 · Core claim 🟡
Content-critical question only partially held
+2 pts
From: Q8 · Severity of the miss (overall human judgment) 🟡
Concordant (toward reproduced)
Code + data deposited & functional
-2 pts
From: Data & code availability Available & functional
Total score +2

Where tested, this reproduces cleanly: data ships in-repo and the shape (8023×1046, 28 classes) plus 3 full-feature accuracies match within run-to-run noise (2 exact <0.0005, PassiveAggressive within 0.0091). The only deviations are stochastic — the original code sets no random seed, so bit-exactness is impossible by design; deviations are on the technical/expected side, not authors' or data. However, the paper's headline contribution — the 100-miRNA signature ≈ full-feature accuracy (1.4% gap) — and 5 compute-heavy classifiers were never collected (job cancelled at ~35min), so the core claim is supported in spirit but not numerically confirmed: a fuller run is needed.

🤝
Reproduced automatically — and fairly

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.

Are you an author? We would genuinely like to hear from you — to clarify the record, add data or code, re-run the pipeline after an accession update, and publish your response right next to the assessment. Everything here is open and auditable.

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Reproduction footprint

claude-opus-4-8

Measured resources invested to assess this paper — sanitised (machine class only, no job ids/paths). Compute = HPC accounting (SLURM); tokens = the AI agent's session.

161.4 k
tokens (I/O) · 12.5 M incl. cache
43 min
runtime · 0.78 CPU-h
1.9 GB
peak RAM
2 (1 failed)
HPC jobs
hummel
machine