WikiPathways: Pathway Models for Network Analysis

1. WikiPathways
Pathway Models for Network Analysis
Martina Summer-Kutmon, PhD
Maastricht Centre for Systems Biology (MaCSBio)
Department of Bioinformatics (BiGCaT)
Maastricht University
4 September 2020
BioNetVisA 2020 workshop

2. Acknowledgements
core development and curation team
and many contributors and curators
around the world

3. WikiPathways Introduction
Slenter DN, Kutmon M, Hanspers K, Riutta A, Windsor J, Nunes N, Mélius J, Cirillo E, Coort SL,
Digles D, Ehrhart F, Giesbertz P, Kalafati M, Martens M, Miller R, Nishida K, Rieswijk L,
Waagmeester A, Eijssen LMT, Evelo CT, Pico AR, Willighagen EL
WikiPathways: a multifaceted pathway database bridging metabolomics to other omics research.
Nucleic Acids Res. 2018 Jan 4;46(D1):D661-D667. doi: 10.1093/nar/gkx1064.

4. WikiPathways
• Launched in 2008 as an experiment in
community-based curation of biological pathways
Too much data!
Difficult to keep knowledge
up-to-date, accessible and
integrated
Taking advantage of direct
participation by a greater portion
of the community (crowdsourcing)
Image:
https://www.vizioninteractive.com/blog/data-overload-when-it-all-becomes-too-much/

5. WikiPathways
• A wikipedia for pathways
- Build on MediaWiki (same software wiki package as
used by wikipedia.org)
- Collection and curation of knowledge
- Community curated
- Everybody can contribute pathways
- Everybody can edit and curate pathways
- Everybody can use the pathway collections

6. WikiPathways
• Advantages
- Fast
- New findings can be added immediately
- Collaborative
- Researchers can exchange ideas and discuss pathways
- Collaborations with other manually curated pathway
databases (Reactome, NetPath)
- Flexible
- Pathways under development or hypothetical pathways
- Disease specific pathways
- Cell-type specific pathways

7. Pathway pages
https://www.wikipathways.org/index.php/Pathway:WP545
Title
Authors
Clickable diagram
Quality tags
Ontology tags
Bibliography
History
Discussion page
Download

8. Community portals
• Special interest groups
• Portal pages to highlight communities

9. COVID-19 portal
• Collaboration within the
COVID-19 DiseaseMap project
• Ongoing curation effort
• Grant for curation and development of new
software features
COVID-19 Disease Map, building a computational repository of
SARS-CoV-2 virus-host interaction mechanisms (2020)
https://doi.org/10.1038/s41597-020-0477-8

10. Content and coverage

11. WikiPathways content
• Statistics
- 2,887 pathways
- 739 contributors
• August 2020 release
- Curated collection
- 1,998 pathways in 25 species
- Focus still mainly on human pathways
- In the last month: edits from 21 contributors (165
edits)
Images:
https://cybra.com/wp-content/uploads/2015/09/statistics.png

12. Data accessibility
• Download
- For each pathway
- Collections in monthly releases
• Data formats
- GPML (graphical pathway markup language)
- PNG, SVG, PDF (images)
- BioPAX (biological pathway exchange language)
- Gene lists / GMT files

13. Data accessibility
• Programmatic access
- REST API
- RDF, semantic web
- rWikiPathways
- Cytoscape app
- NDEx
- wikidata

14. User stats
• Statistics in the last year
- ~15k-20k visitors a month
- >500,000 REST webservice requests per month

15. Human gene coverage
40% of protein-coding
genes not present in
any pathway db
Only ~300 not
protein-coding genes
Many protein-coding genes
only present in one of the databases
577 (KEGG), 710 (WP), 3,320 (Reactome)Data December 2018

16. Missing knowledge
Extracting information from pathway figures

17. Improving coverage
Published
figures of
pathways
WikiPathways
Anders Riutta Alex Pico
Identifying Genes in Published Pathway Figure Images (2018)
https://doi.org/10.1101/379446

18. Difficulty level of pathway figures

19. Publications with pathway figures
• PubMed Central image search for a set of
pathway types
- 235,000 figure between 1995 and 2020
• Classification of figures
- Machine learning -> 64,643 actual pathway figures
• OCR to identify genes in pathway figures
- Interesting gene sets that can be used to prioritize
curation and perform enrichment analysis
25 Years of Pathway Figures (2020)
https://doi.org/10.1101/2020.05.29.124503

20. Interactive query tool
https://gladstone-bioinformatics.shinyapps.io/shiny-25years/

21. Network analysis

22. Pathway / Network view
WikiPathways App for Cytoscape: Making biological pathways
amenable to network analysis and visualization
(2014) https://doi.org/10.12688/f1000research.4254.2

23. Network analysis
Gene-pathway associations
Automatic extension
CyTargetLinker app update: A flexible solution
for network extension in Cytoscape (2019)
https://doi.org/10.12688/f1000research.14613.2

24. Pathway overlap / connections
Primary open‐angle glaucoma
Molecular pathogenesis
Comprehensive bioinformatics analysis of trabecular
meshwork gene expression data to unravel the molecular
pathogenesis of primary open‐angle glaucoma (2020)
https://doi.org/10.1111%2Faos.14154Ilona Liesenborghs

25. Active module analysis
Beyond Pathway Analysis: Identification of
Active Subnetworks in Rett Syndrome (2019)
https://doi.org/10.3389%2Ffgene.2019.00059
Ryan Miller
Network of all pathways
Active modules

26. Metabolic pathways
Denise Slenter
Sparse metabolic data
Pathway crosstalk
Manuscript in preparation

27. Summary
• WikiPathways – collaborative pathway database
• Open source / open data
• Easy programmatic access
• Pathway visualization in PathVisio/Cytoscape
• Network representations of pathway data
- RDF, Neo4j, Gene-Pathway networks
• Network analysis in Cytoscape

28. Thank you for your attention
Questions?
Martina Summer-Kutmon
martina.kutmon@maastrichtuniversity.nl
twitter: mkutmon