1. The Pathway Tools Schema

2. SRI International Bioinformatics 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 When writing complex queries to PGDBs, those queries must name classes and slots within the schema A Pathway/Genome Database is a web of interconnected objects; each object represents a biological entity

3. SRI International Bioinformatics Reference Pathway Tools User’s Guide, Volume I l Appendix A: Guide to the Pathway Tools Schema

4. SRI International Bioinformatics Web of Relationships for One Enzyme Sdh-flavoSdh-Fe-SSdh-membrane-1Sdh-membrane-2 sdhAsdhB sdhCsdhD Succinate + FAD = fumarate + FADH 2 Enzymatic-reaction Succinate dehydrogenase TCA Cycle

5. SRI International Bioinformatics Frame Data Model Frame Data Model -- organizational structure for a PGDB Knowledge base (KB, Database, DB) Frames Slots Facets Annotations

6. SRI International Bioinformatics Knowledge Base Collection of frames and their associated slots, values, facets, and annotations AKA: Database, PGDB Can be stored within l An Oracle or MySQL DB l A disk file l Pathway Tools binary program

7. SRI International Bioinformatics Frames Entities with which facts are associated Kinds of frames: l Classes: Genes, Pathways, Biosynthetic Pathways l Instances (objects): trpA, TCA cycle Classes: l Superclass(es) l Subclass(es) l Instance(s) A symbolic frame name (id, key) uniquely identifies each frame

8. SRI International Bioinformatics Slots Encode attributes/properties of a frame l Integer, real number, string Represent relationships between frames l The value of a slot is the identifier of another frame Every slot is described by a “slot frame” in a KB that defines meta information about that slot

9. SRI International Bioinformatics Slot Links Sdh-flavoSdh-Fe-SSdh-membrane-1Sdh-membrane-2 sdhAsdhB sdhCsdhD Succinate + FAD = fumarate + FADH 2 Enzymatic-reaction Succinate dehydrogenase TCA Cycle product component-of catalyzes reaction in-pathway

10. SRI International Bioinformatics Slots Number of values l Single valued l Multivalued: sets, bags Slot values l Any LISP object: Integer, real, string, symbol (frame name) Slotunits define properties of slots: datatypes, classes, constraints Two slots are inverses if they encode opposite relationships l Slot Product in class Genes l Slot Gene in class Polypeptides

11. SRI International Bioinformatics Representation of Function Sdh-flavoSdh-Fe-SSdh-membrane-1Sdh-membrane-2 sdhAsdhB sdhCsdhD Succinate + FAD = fumarate + FADH 2 Enzymatic-reaction Succinate dehydrogenase TCA Cycle EC# K eq Cofactors Inhibitors Molecular wt pI Left-end-position

12. SRI International Bioinformatics Monofunctional Monomer Gene Reaction Enzymatic-reaction Monomer Pathway

13. SRI International Bioinformatics Bifunctional Monomer Gene Reaction Enzymatic-reaction Monomer Pathway Reaction Enzymatic-reaction

14. SRI International Bioinformatics Monofunctional Multimer Monomer Gene Reaction Enzymatic-reaction Multimer Pathway

15. SRI International Bioinformatics Pathway and Substrates Reactant-1 Reaction Pathway Reaction Reactant-2 Product-2 Product-1 in-pathway left right

16. SRI International Bioinformatics Transcriptional Regulation site001 pro001 trpE trpD trpC trpB trpA trpL Int003RpoSig70 TrpR*trpInt001 trpLEDCBA trp apoTrpR Int005

17. SRI International Bioinformatics Annotations Encode information about individual slot values Used to attach comments and citations to slot values Example: l Frame tryptophan-synthetase has a slot called Molecular- Weight with a value of 28 l Attached to that value is an annotation whose label is Citation and whose value is “[3444332]”

18. SRI International Bioinformatics Facets Encode information about slots Allow association between a slot and: l comments l citations Example: Comment attached to Inhibitors of EnzRxn Allow access to schema information

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

20. SRI International Bioinformatics Principle Classes Reactions, with subclasses: l Transport-Reactions Enzymatic-Reactions Pathways Compounds-And-Elements

21. SRI International Bioinformatics Frame IDs of Instances Instance frame ID conventions have evolved over time Examples: l Pathways u TRPSYN-PWY, P23-PWY l Genes u AG10045 l Monomers u TRPA-MONOMER, AG10045-MONOMER

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

23. SRI International Bioinformatics Genes Slots Component-Of (links to replicon, transcription unit) Left-End-Position Right-End-Position Centisome-Position Transcription-Direction Product

24. SRI International Bioinformatics Proteins Slots Molecular-Weight-Seq Molecular-Weight-Exp pI Locations Modified-Form Unmodified-Form Component-Of

25. SRI International Bioinformatics Polypeptides Slots Gene

26. SRI International Bioinformatics Protein-Complexes Slots Components

27. SRI International Bioinformatics Reactions Slots EC-Number Left, Right Substrates (computed as union of Left, Right) DeltaG0 Keq Spontaneous?

28. SRI International Bioinformatics Enzymatic-Reactions Slots Enzyme Reaction Activators Inhibitors Physiologically-Relevant Cofactors Prosthetic-Groups Alternative-Substrates Alternative-Cofactors

29. SRI International Bioinformatics Pathways Slots Reaction-List Predecessors Primaries