WikiPathways App for Cytoscape: Making biological pathways amenable to network analysis and visualization.
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.
- ✓No authors-side cause for any deviation
- ✓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
- 🟡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
Reproduced this paper at the code + data level rather than 1:1 GUI level. The app (a 2014 Cytoscape 3 plugin) builds cleanly from source today only after two disclosed environment-level fixes: substituting the dead code.cytoscape.org/http-only Maven repos with their live successors (NRNB Nexus, HTTPS Central), and running the repo's own documented localsetup.sh to install its vendored third-party jars (pathvisio-core, bridgedb, bridgedb-bio, derby) that no longer exist on any public Maven repo under their original 2014 coordinates -- this is drift in the Java dependency ecosystem over 12 years, not a flaw in the paper. Two of the paper's core methodological/results claims were independently verified by parsing the underlying data directly (not by running the built app's GUI, which was out of scope here): (1) the pathway-to-network 'redundant nodes merged' claim is structurally confirmed in WP2795's GPML (8 duplicate identifiers across 17 DataNode instances collapsing to 8 unique nodes); (2) the 'Entrez Gene mapped to Ensembl via BridgeDb to match the dataset' claim is confirmed quantitatively (96% overlap between pathway-derived Ensembl IDs and the dataset's Ensembl IDs), though using an equivalent authoritative mapping service (MyGene.info) rather than literally running BridgeDb's Derby-backed IDMapper, because that specific module was not vendored in the repo (only the text-file and webservice IDMapper implementations were present). NOT attempted: headless GUI execution of the actual Cytoscape app (Figures 1/2's NetworkAnalyzer overlay and jActiveModules run) -- a scope decision, not a failure. NOT obtained: the paper-cited historical GPML revision WP2795_r76316 (only the current, much-later-edited r139973 could be fetched; wikipathways.org now blocks the legacy revision-download routes with Cloudflare 403, confirmed after 4 distinct URL/API attempts). A genuine, disclosed inconsistency was found in the RNA-seq dataset: the paper's own caption text describes it as comparing 'time point 6 hrs vs. control', but the actual downloaded file's columns are named 'log_fold-D60_vs_D00' etc. -- flagged, not resolved, since the original PMC-hosted supplementary .tgz could not be downloaded (blocked by PMC's cloudpmc-viewer bot-protection) to cross-check against this substitute F1000Research-CDN-hosted .xlsx.
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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
- 2026-08-03
- Rubric version
- v1.0
- Assessed by
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🤖 AI curator · claude (ai-curator room) · v1.0 · run #1 2026-08-03no human curator yet
- Last updated
- 2026-08-03
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- ★ The open-source WikiPathways app for Cytoscape imports biological pathways from WikiPathways for data visualization and network analysis. resource
- ★ The app can load pathways in two distinct views: an annotated pathway preserving the original visual layout (ideal for data visualization) and a simplified node-and-edge network (ideal for computational/topological analysis). method
- ★ Transforming an arbitrary XML format like GPML into even a basic Cytoscape import format is impractical without this dedicated app. finding
- ★ The app provides an OSGi-registered API so other Cytoscape apps can query the WikiPathways web services and import GPML files without bundling the WikiPathways app. method
- ★ A DelayedVizProp class was created to store desired node/edge visual styles until Cytoscape creates the view objects after network construction. method
- The app was rewritten from its predecessor, the GPML Plugin, to use the new Cytoscape 3 OSGi-based architecture (Cytoscape API version 3.0.0). method
- OSGi insulation hides the bundled PathVisio core library from other Cytoscape apps and modules, preventing library conflicts. mechanism
- Apache HTTP Client is used instead of java.net.HttpURLConnection so that HTTP requests to the WikiPathways REST server can be cancelled, keeping the user interface responsive. method
| Assay | System | Perturbation | Readout | Platform |
|---|---|---|---|---|
| RNA-seq (unpublished dataset, subset covering all genes in the pathway) | cardiac stem cells (human Cardiac Hypertrophic Response pathway, WP2795) | differentiation time course; comparison 'time point 6 hrs vs. control' | logFC, p-value and adjusted p-value per gene | — |
| Pathway import and data visualization as annotated pathway view | Cytoscape 3 with WikiPathways app; human Cardiac Hypertrophic Response pathway (WP2795) | none | logFC as node fill color (blue-white-red gradient), adjusted p-value < 0.05 as green node border, unmeasured elements grey | Cytoscape 3 (API version 3.0.0); WikiPathways web services; PathVisio core library; Apache HTTP Client |
| Pathway import as simplified network view | Cytoscape 3 with WikiPathways app; Cardiac Hypertrophic Response pathway | none | network of biological entities and interactions with graphical annotations removed, redundant nodes merged, force-directed layout | Cytoscape 3 |
| Network topology analysis | Cardiac Hypertrophic Response pathway loaded as network in Cytoscape | none | node degree and betweenness to identify hub nodes | Cytoscape built-in NetworkAnalyzer |
| Active subnetwork detection | Cardiac Hypertrophic Response network in Cytoscape with cardiac stem cell RNA-seq data | none | active subnetworks affected by varying gene expression (highlighted in purple) | jActiveModules Cytoscape app |
| Identifier mapping | Cardiac Hypertrophic Response pathway in Cytoscape | none | Entrez Gene identifiers mapped to Ensembl to match dataset identifiers | BridgeDb Cytoscape app |
| App adoption/usage tracking | Cytoscape App Store | none | number of app downloads | Cytoscape App Store (http://apps.cytoscape.org/apps/wikipathways) |
- – More than 3000 downloads in the first 12 months following the app's release in August 2013, highlighting its adoption in the network biology field. > 3000 downloads in 12 months
- – The Cardiac Hypertrophic Response pathway loaded as an annotated pathway preserves the exact layout and graphical elements of the WikiPathways original, onto which logFC data were mapped as node fill color.
- – Loaded as a network, graphical annotations are removed and redundant nodes are merged into single unique nodes, with groups and complex interactions shown as very small nodes under a force-directed layout.
- – NetworkAnalyzer computed node degree and betweenness on the imported network to identify important hub nodes.
- – jActiveModules identified active subnetworks affected by varying gene expression in the imported network.
- – BridgeDb mapping of Entrez Gene to Ensembl identifiers enabled integration of the RNA-seq dataset with the pathway nodes.
- – The DelayedVizProp approach resolved the inability to assign visual styles to nodes/edges before their view objects exist during network construction.
- count More than 3000 downloads (app downloads in the first 12 months after the August 2013 release)
- pvalue adjusted p-value < 0.05 (threshold for significant measurements highlighted with green node border in Figures 1 and 2C)
- other Cytoscape API version 3.0.0 (Cytoscape API version targeted by the app)
- other time point 6 hrs vs. control (comparison from which logFC values in the example dataset were derived)
Statistical methods review
Model: sonnetA 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 software tool paper describing the WikiPathways app for Cytoscape and does not report an original hypothesis-driven statistical analysis of its own. To demonstrate the app's visualization features, the authors use an example, unpublished RNA-seq dataset (comparing a 6-hour timepoint vs. control during cardiac stem cell differentiation) that already contains per-gene logFC, p-value, and adjusted p-value columns; the app visualizes logFC as node color and flags genes with adjusted p-value < 0.05 with a green border, but the manuscript does not describe how those values were computed.
| Test | Applied to | n | Assumptions |
|---|---|---|---|
| Differential expression analysis (test/model not specified) yielding logFC, p-value, and adjusted p-value per gene | Example RNA-seq dataset used to demonstrate pathway visualization (Figure 1, Figure 2C), comparing timepoint 6 hrs vs. control | — | not stated |
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The example dataset reports differential expression results (logFC, p-value, adjusted p-value) without the manuscript stating which analysis tool or statistical model generated them.↳ Could also: Naming and citing a specific RNA-seq differential expression tool (e.g. DESeq2, edgeR, or limma-voom) — Explicitly stating the model and correction method used to produce the underlying values would let readers see how the numbers driving the visualization were derived, complementing the app's own documentation of its visualization logic.
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Significance is encoded as a single binary indicator (green border for adjusted p-value < 0.05) rather than a continuous measure.↳ Could also: Continuous visual encoding of -log10(adjusted p-value), e.g. via node border thickness or color intensity — A continuous encoding would convey relative strength of significance across genes in addition to the pass/fail threshold already shown, giving an additional way to compare genes on the pathway.
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The manuscript uses the term 'adjusted p-value' without specifying the multiple-testing correction method behind it.↳ Could also: Explicitly citing the correction approach (e.g. Benjamini-Hochberg FDR or Bonferroni) — Naming the specific correction method would let readers relate the stringency of the highlighted genes to standard reference points used elsewhere in the field.
What was reproduced
The exact results taken into scope, with each reported value next to the value our attempt produced.
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 software/tools paper: the app builds cleanly from source to a valid 5,493,330-byte OSGi bundle (WikiPathways-3.3.11.jar) once two purely environmental fixes are applied — dead Maven repos (code.cytoscape.org 404, plain-HTTP Central 501) mirrored to NRNB Nexus/HTTPS Central, plus the repo's own documented localsetup.sh for vendored 2014 jars. Both substantive methodological claims are confirmed from the shared data: WP2795's GPML contains 8 identifiers drawn 2–3 times (17 DataNode instances → 8 unique nodes), matching the redundant-node-merging claim, and 54/54 pathway Entrez IDs map to Ensembl with 49/51 (96%) overlap against the RNA-seq dataset. The deviations sit on our/environment side and are disclosed: the paper-cited GPML revision r76316 is unobtainable (Cloudflare 403), MyGene.info replaced the non-vendored org.bridgedb.rdb Derby IDMapper, and the Figure 1/2 GUI run was an explicit out-of-scope decision. The one authors'-side blemish is a caption/data contradiction ('6 hrs vs. control' vs columns log_fold-D60_vs_D00) — a labelling defect, not a derivability or integrity problem, so q5/q7 stay green and q8 is yellow.
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