The Pathway Tools Schema

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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 “[ ]”

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

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

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

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

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

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

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

SRI International Bioinformatics Polypeptides Slots Gene

SRI International Bioinformatics Protein-Complexes Slots Components

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

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

SRI International Bioinformatics Pathways Slots Reaction-List Predecessors Primaries