1. Ministry of Economic Development and Innovation
Reforming Reactome
Robin Haw th August COMBINE – Toronto Meeting
Ministry of Economic Development and Innovation

2. What is Reactome? Open source and open access pathway database
1300+ human pathways encompassing metabolism, signaling, gene regulation, and other biological processes
Extensively cross-referenced to external bioinformatics databases
Tools and datasets for browsing and visualizing pathway data, and interpreting your experimental data.

3. Data model in a nutshell
Reactome is a Reaction Network Database
Explicitly describe biological processes as a series of biochemical reactions and events
Represents many events and states found in biology.
location
(GO cell component)
protein (UniProt) or
molecule (ChEBI) or
complex (GO/PRO) or
ncRNA (miRBase) or
disease variants (UniProt)
therapeutics (ChEBI)
CatalystActivity
(GO mol function)
Output 1
Reaction
Input 1
Input 2
Output 2
Regulation
(GO biol process)

4. Pathways in Other Databases
Curation Pipeline
Author Tool
Curator Tool
CGI Scripts
Web Pages
Reviewer
Dev DB
Data Expansion by electronic inference using mutual best hits from human to model organisms
RC DB
Live DB
Author
Curator
BioPAX Importer
SBML Importer
KGML Importer
Pathways in Other Databases
Automated Curation
Manual Curation

5. Focus on Disease Topics
Not new to Reactome!
Reorganized the Pathway Hierarchy.
Modified the Data Model.
Updating the Pathway Browser.
Annotate:
An infection introduces new proteins into the cell.
The amount of a normal protein is changed and this changes the function of the protein.
A mutation (somatic or germline) changes the function of a protein.
Mode of action of anti-cancer therapeutics and antibodies.

6. Disease Curation We need a more systematic disease ontology!
Details of EGFRvIII mutant in Signaling by EGFR in Cancer
Reactome need to annotate “disease” proteins and their functions in a way that allows these variant proteins and processes to be integrated seamlessly with the rest of Reactome, just as we already seamlessly integrate signaling and DNA replication and metabolism.
For example, if you were browsing the Details Panel of EGFRvIII mutant, you’d see the types of cancers that have the same mutations. If you were then to click the link labelled “adult glioblastoma cells”, you would be taken to another webpage listing the source of this disease annotation and other mutations that are asociated with GBM.

7. Pathway Browser Divide reaction space into ~170 canonical pathways
Amyloid Pathway
Google-map style pathway diagrams with overlays

8. Open access and open source data
MySQL db
ID Mapping
Interactions
GOA
SBML
BioPAX
GSEA
Protege
Textbook
Local install
Author tool
Curator tool
Reactome FI

9. Reactome supports Data Standards
Available for single pathways.
SBML level 2.3.
Available for single pathways or for the whole database.
BioPAX level 2 & 3.
Available for single pathways or for the whole database.
PSICQUIC is an effort to standardize the access to molecular interaction databases.
PSI-MITAB is the data exchange format.

10. Interaction Overlay using PSICQUIC Visualizing Protein-protein Interactions
Download molecular interaction data as PSI-MITAB file

11. SBGN Export

12. SBML Exporter

13. Continuing Priorities
Increase the number of curated proteins and other functional entities.
Supplement normal pathways with variant reactions representing disease states.
Improve annotation consistency and enrich the data model.
Continued support for SBGN, SBML, BioPAX and PSI.
Enhance the web site and other resources to meet the needs of a growing and diverse user community.

14. Ministry of Economic Development and Innovation
Acknowledgements
Marija Orlic-Milacic
Steve Jupe
Karen Rothfels
Bruce May
Lisa Matthews
Antonio Fabregat Mundo
Marc Gillespie
Veronica Shamovsky
Guanming Wu
Heeyeon Song
Irina Kalatskaya
Joel Weiser
Christina Yung
Mark Williams
Michael Caudy
Henning Hermjakob
David Croft
Peter D’Eustachio
Adrian Duong
Lincoln Stein
Phani Garapati
Bijay Jassal
Ministry of Economic Development and Innovation