The WikiPathways App for Cytoscape: How Open Peer Review Built a Bridge for Biological Discovery
Transforming static pathway images into dynamic, analyzable networks through collaborative science
Navigating the Maze of Biological Pathways
Imagine trying to solve the world's most complex subway system without a map—where trains are molecules, stations are cellular processes, and the routes are biochemical reactions that keep us alive.
This is the challenge biologists face when studying biological pathways, the intricate networks of molecular interactions that underlie health and disease. For decades, these pathways existed as static images in journal articles—beautiful to look at but impossible to analyze computationally or connect to experimental data 1 9 .
The scientific community needed a solution—a way to transform these biological roadmaps from mere pictures into dynamic, analyzable networks. This is where the story of the WikiPathways App for Cytoscape begins, a tool that didn't just emerge fully formed but was refined through the transparent process of open peer review—a revolutionary approach where reviewer comments and author responses are published alongside the final paper 1 9 .
In this article, we'll explore how this innovative software tool came to be, how it evolved through community feedback, and how it's helping researchers worldwide visualize their data in the context of biological pathways to make groundbreaking discoveries.
Democratizing Pathway Analysis: From Static Images to Living Networks
What is WikiPathways?
WikiPathways is like the Wikipedia of biological pathways—an open, collaborative platform where researchers from around the world can create, edit, and share pathway diagrams 1 9 .
But unlike traditional images, these pathways are more than just pictures; they're richly annotated models where every element—genes, proteins, metabolites—is tagged with database identifiers that computers can understand. This transforms pathways from static illustrations into computable resources that can be analyzed, updated, and connected to experimental data.
The Power Couple
While WikiPathways provided the content, researchers needed a way to bring these pathways into their data analysis workflow. Enter Cytoscape, a powerful network visualization and analysis software widely used in computational biology 1 9 .
Think of Cytoscape as the Photoshop of biological networks—it allows researchers to visualize complex interactions and overlay experimental data onto these networks.
The WikiPathways App for Cytoscape bridges these two worlds, allowing scientists to seamlessly import pathways directly from WikiPathways into their Cytoscape environment 6 .
Two Views for Different Research Needs
The developers created a clever dual-view system that addresses different research needs:
Pathway View
Preserves the complete visual layout exactly as designed by pathway curators, including all graphical annotations and labels 1 9 . This is ideal for data visualization, allowing researchers to map their experimental results (like gene expression changes) onto a familiar pathway diagram that can be easily interpreted and presented.
Evolution of the WikiPathways App
| Version | Key Improvements | Impact on Research |
|---|---|---|
| 3.0 | Balanced use of visual mappings and bypass values | Made data visualization more straightforward |
| 3.1 | Added Cytoscape commands for scripting | Enabled automation and reproducibility |
| 3.2 | Pathway preview before import | Improved user experience and selection |
| 3.3.8 | Updated security dependencies | Addressed vulnerabilities for safer use |
A Journey Through Open Peer Review: How Feedback Shaped a Better Tool
The Open Peer Review Model
Unlike traditional journals where reviewer comments remain private, F1000Research publishes the complete peer review history alongside the article 1 3 . This transparency provides a rare window into how scientific discourse and collaboration shape research outcomes.
For the WikiPathways App paper, this process led to concrete improvements in both the software and its documentation.
From Comments to Enhancements
The reviewers' feedback, though generally positive, prompted important refinements. The authors received two approved reviews with specific suggestions for improvement. In their response, they adopted the recommended best practice of addressing every comment with specific changes 1 3 .
The open peer review process demonstrates that science is rarely perfect on the first attempt—it evolves through constructive feedback and collaborative refinement. By making this process visible, readers can appreciate not just what the scientists discovered, but how the scientific community works together to strengthen research 3 .
Peer Review Comments and Author Responses
| Reviewer Suggestions | Author Responses | Impact on Final Paper |
|---|---|---|
| Adapted figures and fixed pathway typo | Implemented changes directly | Improved visual clarity and accuracy |
| Extended conclusion | Expanded concluding section | Better contextualization of work |
| N/A | Added BridgeDb reference | Enhanced utility for data integration |
Initial Submission
The authors submitted their manuscript describing the WikiPathways App for Cytoscape.
Reviewer Feedback
Two reviewers provided constructive feedback, suggesting improvements to figures, text, and references.
Author Revisions
The authors addressed all comments, improving clarity and adding important references like BridgeDb.
Publication
The final paper was published alongside the complete peer review history for transparency.
A Scientist's Toolkit: Key Resources for Pathway Analysis
The ecosystem surrounding the WikiPathways App comprises several powerful resources that collectively enable comprehensive pathway analysis:
WikiPathways App
Pathway import and visualization
Bridge between pathway databases and analysis tools
Cytoscape
Network visualization and analysis
Primary platform for exploring biological networks
BridgeDb
Identifier mapping
Connecting datasets with different naming conventions
PathVisio
Pathway editing and creation
Building and annotating new pathway models
CyTargetLinker
Network extension
Adding regulatory interactions to existing pathways
WikiPathways
Pathway repository
Open, collaborative platform for pathway curation
A Hands-On Example: Mapping Cardiac Development
To understand how researchers actually use the WikiPathways App, let's walk through a specific example from the paper that analyzed cardiac stem cell differentiation 1 9 .
The Biological Question
Researchers wanted to understand which pathways are activated during early stages of heart development by tracking gene expression changes in differentiating cardiac stem cells. Specifically, they focused on the Cardiac Hypertrophic Response pathway (WP2795 from WikiPathways), which contains genes and metabolites involved in heart growth and response to stress.
The Methodology
Visualization
Using Cytoscape's visualization capabilities, they colored genes in the pathway based on their expression changes—typically using a blue-to-red color gradient where blue indicates decreased expression and red indicates increased expression 2 .
The Results and Interpretation
The analysis revealed which specific genes in the cardiac hypertrophy pathway were activated during early differentiation. The visual approach allowed researchers to quickly identify functional clusters of genes working together, while the network analysis helped pinpoint potential key regulators of the process.
This example demonstrates the power of combining pathway information with experimental data—rather than looking at genes in isolation, researchers can see how entire systems of molecules work together during biological processes.
Conclusion and Future Directions: The Era of Accessible Pathway Analysis
The WikiPathways App for Cytoscape represents more than just another bioinformatics tool—it embodies the democratization of biological knowledge. By making sophisticated pathway analysis accessible to researchers without computational expertise, it bridges the gap between experimental and computational biology.
The transparent peer review process that shaped the paper demonstrates how scientific collaboration and constructive feedback strengthen research outcomes. As the authors noted in their revision, the app had already been downloaded over 3,000 times in its first year—a number that has undoubtedly grown substantially since 1 9 .
Looking ahead, the principles behind this tool—openness, collaboration, and interoperability—are exactly what science needs to tackle increasingly complex biological questions. As more researchers contribute pathways to WikiPathways and more analysis methods become available in Cytoscape, our ability to understand the intricate networks of life will only deepen.
For students and early-career researchers, this evolution represents an exciting opportunity—the tools that once required specialized programming skills are now at everyone's fingertips, waiting to be explored and applied to the next biological mystery.
The WikiPathways App for Cytoscape is freely available from the Cytoscape App Store, and the peer-reviewed paper, complete with all reviewer comments and author responses, can be accessed on F1000Research.
Key Impacts
- Downloads 3,000+
- Pathway Views Dual System
- Integration Multiple Tools
- Review Process Open