1. NCI-Nature Pathway Interaction Database (http://pid.nci.nih.gov) & the BioPAX (Biological Pathways Exchange) Ontology and Formathttp://pid.nci.nih.gov Kira Anthony Nature Publishing Group July 27, 2011

2. Pathway Interaction Database Expert curated, peer-reviewed database of signaling and regulatory pathways Assemble/visualize pathway networks by query on molecule, predefined pathway, shortest path Export predefined pathways or dynamically generated networks in BioPAX Level 2; Level 3 implementation – in progress (beta-level exports currently on FTP site) PID provides human NCI-Nature curated/Reactome/BioCarta/KEGG data in BioPAX

3. PID and BioPAX A BioPAX aim: To provide complete native representations of the source databases PID became involved in helping to determine BioPAX Levels 2 and 3 specifications General Level 3: Generics & clean-up of transcription/translation Additions/changes to BioPAX Level 2 requested/developed by PID: –Families –PTMs –State –Cleaved subunits of proteins –Evidence code ontology (ECO) –Conditions and biological processes

4. Intro to protein family spec JAM Family UniProt P57087 protein family member Level 2 relationshipXref (type=“protein family member”)  Level 3 (generic) entityReference class

5. Complex family Level 2 the protein family solution didn’t work because the member complex didn’t have a standardized name/identifier which could be cross-referenced. Level 3 the entityReference class does work.

6. PTM (known site) <bp:POSITION-STATUS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">EQUAL 211 SequenceFeature (Level 2) replaced with entityFeature (Level 3). SEQUENCE-FEATURE-LIST (Level 2) replaced with modificationFeature, modificationType (Range: SequenceModificationVocabulary), featureLocation, featureLocationType (Level 3).

7. PTM (unknown site) phosphorylati on sequenceFeature (Level 2) replaced with entityFeature (Level 3). SEQUENCE-FEATURE-LIST (Level 2) replaced with modificationFeature, modificationType (Range: SequenceModificationVocabulary**), featureLocationType (Level 3). But no featureLocation. Level 3 **SequenceModificationVocabulary – PSI-MOD introduced

8. State (abstract) - sequenceParticipant active sequenceFeature (Level 2) replaced with entityFeature (Level 3). SEQUENCE-FEATURE-LIST (Level 2) replaced with memberFeature (Level 3) (generic).

9. State (abstract) - complex FGFR/FGF/S yndecan-2/FRS2 bp:SEQUENCE-FEATURE-LIST pid_f_203202_0X26 ; bp:FEATURE-TYPE active Level 2 resorted to comment: couldn’t put a SEQUENCE-FEATURE on a complex. Level 3 entityFeature class will work here.

10. Cleaved protein subunit FAK1 fragment 2_773-1052 protein subunit; protein id = Q05397; start = 773, stop = 1052 Resorted to a comment for subunit coordinates (Level 2); used unificationXref to the whole protein. entityFeature, fragmentFeature, featureLocation - (Utility class: 0 or more object:SequenceLocation, SequenceInterval) (Level 3).

11. Degradation class A new Degradation class: sub-class of Conversion Relevant for PID terms "degradation" and “proteasomal ubiquitin-dependent protein catabolic process”

12. Condition <bp:CONTROL-TYPE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">ACTIVATION acidic pH Minor changes: Level 2 Syntax – Name; Level 3 Syntax – standardName; Also, control interaction is separate in Level 3

13. Biological process negative regulation of muscle contraction <bp:CONTROL-TYPE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">ACTIVATION

14. Level 4 Workgroups snapshot Visualization and exchange (with SBGN) Semantic web (additional ontologies/CVs) Pathways and models (with SBO, SBML, CellML, Virtual Cell) More details: BioPAX.org

15. Additional resources BioPAX.org – community site (with specifications, documentation, L4 workgroups, BioPAX discuss listserv sign-up etc.) Next meeting: COMBINE: September 3-7, 2011, Heidelberg http://co.mbine.orghttp://co.mbine.org Pathway Commons – portal for data exported in BioPAX http://www.pathwaycommons.org/pc/ http://www.pathwaycommons.org/pc/

16. Acknowledgements NCI Carl Schaefer (now retired) Jeff Buchoff (SRA) Sol Efroni (now Bar Ilan U.) Nature Publishing Group Timo Hannay Assistance with BioPAX Gary Bader (Toronto), Emek Demir (MSKCC), Ethan Cerami (MSKCC), Igor Rodchenkov (Toronto), Benjamin Gross (MSKCC) Emails: k.anthony@us.nature.com & nci-pid@nature.comk.anthony@us.nature.comnci-pid@nature.com