1. The Pathway Tools Schema

2. Motivations for Understanding Schema
Pathway Tools visualizations and analyses depend upon the software being able to find precise information in precise places within a Pathway/Genome DB
A Pathway/Genome Database is a web of interconnected objects; each object represents a biological entity

3. Motivations for Understanding Pathway Tools Schema
When writing complex queries to PGDBs, those queries must refer to classes and slots within the schema
Queries using Lisp, Perl, Java APIs
Queries using Query Page
Queries using Structured Advanced Query Form

4. References Pathway Tools User’s Guide
Appendix A: Guide to the Pathway Tools Schema
Ontology Papers section of
“The outcomes of pathway database computations depend on pathway ontology”
"An Evidence Ontology for use in Pathway/Genome Databases,"
"An ontology for biological function based on molecular interactions,"
"Representations of metabolic knowledge: Pathways,"
"Representations of metabolic knowledge,"

5. Pathway Tools Ontology / Schema
Ontology classes: 1621
Many datatypes from genomes to pathways
Classification schemes for pathways, chemical compounds, enzymatic reactions (EC system)
Cell Component Ontology
Protein Feature ontology
Comprehensive set of 221 attributes and relationships
Evidence codes, supporting citations

6. Root Classes in the Pathway Tools Ontology
Chemicals -- All molecules
Polymer-Segments -- Regions of polymers
Protein-Features -- Features on proteins
Paralogous-Gene-Groups
Organisms
Enzymatic-Reactions -- Link enzymes to reactions they catalyze
Generalized-Reactions -- Reactions and pathways
Regulation -- Defines regulatory interactions
CCO Cell Component Ontology
Evidence Evidence ontology
Notes Timestamped, person-stamped notes
Organizations
People
Publications

7. Principle Classes
Class names are capitalized, plural, separated by dashes
Genetic-Elements, with subclasses:
Chromosomes
Plasmids
Genes
Transcription-Units
RNAs
rRNAs, snRNAs, tRNAs, Charged-tRNAs, Regulatory-RNAs
Proteins, with subclasses:
Polypeptides
Protein-Complexes

8. Principle Classes Reactions, with subclasses: Transport-Reactions
Enzymatic-Reactions
Pathways
Compounds-And-Elements

9. Web of Relationships for One Enzyme
TCA Cycle
Succinate + FAD = fumarate + FADH2
Enzymatic-reaction
Succinate dehydrogenase
Sdh-flavo
Sdh-Fe-S
Sdh-membrane-1
Sdh-membrane-2
sdhA
sdhB
sdhC
sdhD

10. Representation of Function
TCA Cycle
EC#
Keq
Cofactors
Molecular-Weight-Seq
Molecular-Weight-Exp pI
Succinate + FAD = fumarate + FADH2
Enzymatic-reaction
Succinate dehydrogenase
Sdh-flavo
Sdh-Fe-S
Sdh-membrane-1
Sdh-membrane-2
sdhA
sdhB
sdhC
sdhD
Left-end-position

11. Monofunctional Monomer
Pathway
Reaction
Enzymatic-reaction
Monomer
Gene

12. Bifunctional Monomer Pathway Reaction Reaction Enzymatic-reaction
Gene

13. Monofunctional Multimer
Pathway
Reaction
Enzymatic-reaction
Multimer
Monomer
Monomer
Monomer
Monomer
Gene
Gene
Gene
Gene

14. Pathway and Substrates
Reactant-1
Pathway
left
in-pathway
Reactant-2
Reaction
Reaction
Reaction
Reaction
Product-1
right
Product-2

15. Regulation
Reorganization and expansion of regulation under way in Pathway Tools
Initial application to EcoCyc
Class Regulation with subclasses that describe different biochemical mechanisms of regulation
Slots:
Regulator
Regulated-Entity
Mode
Mechanism

16. Regulation of Enzyme Activity
Class Regulation-of-Enzyme-Activity
Each instance of the class describes one regulatory interaction
Slots:
Regulator -- usually a small molecule
Regulated-Entity -- an Enzymatic-Reaction
Mechanism -- One of:
Competitive, Uncompetitive, Noncompetitive, Irreversible, Allosteric, Unkmech, Other
Mode -- One of: + , -

17. Transcription Initiation
Class Regulation-of-Transcription-Initiation
Slots:
Regulator -- instance of Proteins or Complexes (a transcription-factor)
Regulated-Entity -- instance of Promoters or Transcription-Units or Genes
Mode -- One of: + , -

18. Attenuation Class Transcriptional-Attenuation
Several subclasses depending on type of attenuation
Slots common to all:
Regulator -- Depends on subtype of attenuation
Regulated-Entity -- instance of Terminators or Genes or Transcription-Units
Mode -- One of: + , -

19. Attenuation Subtypes Small-Molecule-Mediated-Attenuation
Regulator = A small molecule
Leader transcript binds small molecule and determines formation of terminator or antiterminator
RNA-Polymerase-Modification
Regulator = instance of Proteins or Complexes
Regulatory protein binds to site in transcription unit and interacts with RNA polymerase to determine termination
RNA-Mediated-Attenuation
Ribosome-Mediated-Attenuation
Rho-Blocking-Antitermination
Protein-Mediated-Attenuation

20. Frame IDs of Instances
Instance frame ID conventions have evolved over time
Examples:
Pathways
TRPSYN-PWY, P23-PWY
Genes
AG10045
Monomers
TRPA-MONOMER, AG10045-MONOMER

21. Slots in Multiple Classes
Common-Name
Synonyms
Names (computed as union of Common-Name, Synonyms)
Comment
Citations
DB-Links

22. Genes Slots Component-Of (links to replicon, transcription unit)
Left-End-Position
Right-End-Position
Transcription-Direction
Product

23. Proteins Slots Molecular-Weight-Seq Molecular-Weight-Exp pI Locations
Modified-Form
Unmodified-Form
Component-Of

24. Polypeptides Slots
Slots inherited from Proteins
Gene

25. Protein-Complexes Slots
Slots inherited from Proteins
Components

26. Reactions Slots
EC-Number
Left, Right
DeltaG0
Keq
Spontaneous?

27. Enzymatic-Reactions Slots
Enzyme
Reaction
Cofactors
Prosthetic-Groups
Alternative-Substrates

28. Pathways Slots
Reaction-List
Predecessors
Primaries

29. Inspecting PGDB Instance Frames
Right-click on object handles to find frame-id
Show menu allows printing of frames

30. Inspecting PGDB Schema
Invoke GKB Editor Taxonomy Browser:
(gkb) or
Right-click: Edit  Ontology Editor
Invoke GKB Editor frame editor:
Right-click: Edit  Frame Editor
Information about GKB Editor:
User Guide:
Publication: