The Pathway Tools Schema

SRI InternationalBioinformaticsMotivations 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 InternationalBioinformaticsReference

Pathway Tools User’s Guide, Volume I Appendix A: Guide to the Pathway Tools Schema

SRI InternationalBioinformaticsWeb of Relationships for One

Enzyme

Sdh-flavo Sdh-Fe-S Sdh-membrane-1 Sdh-membrane-2

sdhA sdhB sdhC sdhD

Succinate + FAD = fumarate + FADH2

Enzymatic-reaction

Succinate dehydrogenase

TCA Cycle

SRI InternationalBioinformaticsFrame Data Model

Frame Data Model -- organizational structure for a PGDB

Knowledge base (KB, Database, DB)

Frames

Slots

Facets

Annotations

SRI InternationalBioinformaticsKnowledge Base

Collection of frames and their associated slots, values, facets, and annotations

AKA: Database, PGDB

Can be stored within An Oracle or MySQL DB A disk file Pathway Tools binary program

SRI InternationalBioinformaticsFrames

Entities with which facts are associated

Kinds of frames: Classes: Genes, Pathways, Biosynthetic Pathways Instances (objects): trpA, TCA cycle

Classes: Superclass(es) Subclass(es) Instance(s)

A symbolic frame name (id, key) uniquely identifies each frame

SRI InternationalBioinformaticsSlots

Encode attributes/properties of a frame Integer, real number, string

Represent relationships between frames 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 InternationalBioinformaticsSlot Links

Sdh-flavo Sdh-Fe-S Sdh-membrane-1 Sdh-membrane-2

sdhA sdhB sdhC sdhD

Succinate + FAD = fumarate + FADH2

Enzymatic-reaction

Succinate dehydrogenase

TCA Cycle

product

component-of

catalyzes

reaction

in-pathway

SRI InternationalBioinformaticsSlots

Number of values Single valued Multivalued: sets, bags

Slot values 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

Slot Product in class Genes Slot Gene in class Polypeptides

SRI InternationalBioinformaticsRepresentation of Function

Sdh-flavo Sdh-Fe-S Sdh-membrane-1 Sdh-membrane-2

sdhA sdhB sdhC sdhD

Succinate + FAD = fumarate + FADH2

Enzymatic-reaction

Succinate dehydrogenase

TCA Cycle

EC#Keq

CofactorsInhibitors

Molecular wtpI

Left-end-position

SRI InternationalBioinformaticsMonofunctional Monomer

Gene

Reaction

Enzymatic-reaction

Monomer

Pathway

SRI InternationalBioinformaticsBifunctional Monomer

Gene

Reaction

Enzymatic-reaction

Monomer

Pathway

Reaction

Enzymatic-reaction

SRI InternationalBioinformaticsMonofunctional Multimer

Monomer Monomer Monomer Monomer

Gene Gene Gene Gene

Reaction

Enzymatic-reaction

Multimer

Pathway

SRI InternationalBioinformaticsPathway and Substrates

Reactant-1

Reaction

Pathway

ReactionReactionReaction

Reactant-2

Product-2

Product-1

in-pathwayleft

right

SRI InternationalBioinformaticsTranscriptional Regulation

site001

pro001

trpE

trpD

trpC

trpB

trpA

trpL

Int003 RpoSig70

TrpR*trpInt001

trpLEDCBA

trp

apoTrpRInt005

SRI InternationalBioinformaticsPrinciple Classes

Class names are capitalized, plural, separated by dashes

Genetic-Elements, with subclasses: Chromosomes Plasmids

Genes Transcription-Units RNAs

rRNAs, snRNAs, tRNAs, Charged-tRNAs Proteins, with subclasses:

Polypeptides Protein-Complexes

SRI InternationalBioinformaticsPrinciple Classes

Reactions, with subclasses: Transport-Reactions

Enzymatic-Reactions

Pathways

Compounds-And-Elements

SRI InternationalBioinformaticsFrame IDs of Instances

Instance frame ID conventions have evolved over time

Examples: Pathways

TRPSYN-PWY, P23-PWY Genes

AG10045 Monomers

TRPA-MONOMER, AG10045-MONOMER

SRI InternationalBioinformaticsSlots in Multiple Classes

Common-NameSynonymsNames (computed as union of Common-Name,

Synonyms)

CommentCitations

DB-Links

SRI InternationalBioinformaticsGenes Slots

Component-Of (links to replicon, transcription unit)

Left-End-PositionRight-End-PositionCentisome-PositionTranscription-DirectionProduct

SRI InternationalBioinformaticsProteins Slots

Molecular-Weight-SeqMolecular-Weight-Exp

pILocations

Modified-FormUnmodified-Form

Component-Of

SRI InternationalBioinformaticsPolypeptides Slots

Gene

SRI InternationalBioinformaticsProtein-Complexes Slots

Components

SRI InternationalBioinformaticsReactions Slots

EC-Number

Left, RightSubstrates (computed as union of Left, Right)

DeltaG0Keq

Spontaneous?

SRI InternationalBioinformaticsEnzymatic-Reactions Slots

EnzymeReactionActivatorsInhibitorsPhysiologically-RelevantCofactorsProsthetic-GroupsAlternative-SubstratesAlternative-Cofactors

SRI InternationalBioinformaticsPathways Slots

Reaction-ListPredecessorsPrimaries