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

A Pathway/Genome Database is a web of interconnected objects; each object represents a biological entity

SRI InternationalBioinformaticsMotivations 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

SRI InternationalBioinformaticsReferences

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

Ontology Papers section of http://biocyc.org/publications.shtml

“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,"

SRI InternationalBioinformaticsPathway 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

SRI InternationalBioinformatics

Root Classes in the Pathway ToolsOntology

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

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, Regulatory-RNAs Proteins, with subclasses:

Polypeptides Protein-Complexes

SRI InternationalBioinformaticsPrinciple Classes

Reactions, with subclasses: Transport-Reactions

Enzymatic-Reactions

Pathways

Compounds-And-Elements

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 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

Cofactors

Molecular-Weight-SeqMolecular-Weight-ExppI

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 InternationalBioinformaticsRegulation

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

SRI InternationalBioinformaticsRegulation of Enzyme Activity

Class Regulation-of-Enzyme-ActivityEach 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: + , -

SRI InternationalBioinformaticsTranscription 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: + , -

SRI InternationalBioinformaticsAttenuation

Class Transcriptional-AttenuationSeveral 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: + , -

SRI InternationalBioinformaticsAttenuation Subtypes

Small-Molecule-Mediated-Attenuation Regulator = A small molecule Leader transcript binds small molecule and determines

formation of terminator or antiterminatorRNA-Polymerase-Modification

Regulator = instance of Proteins or Complexes Regulatory protein binds to site in transcription unit and

interacts with RNA polymerase to determine terminationRNA-Mediated-AttenuationRibosome-Mediated-AttenuationRho-Blocking-AntiterminationProtein-Mediated-Attenuation

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-PositionTranscription-DirectionProduct

SRI InternationalBioinformaticsProteins Slots

Molecular-Weight-SeqMolecular-Weight-Exp

pILocations

Modified-FormUnmodified-Form

Component-Of

SRI InternationalBioinformaticsPolypeptides Slots

Slots inherited from Proteins

Gene

SRI InternationalBioinformaticsProtein-Complexes Slots

Slots inherited from Proteins

Components

SRI InternationalBioinformaticsReactions Slots

EC-Number

Left, Right

DeltaG0Keq

Spontaneous?

SRI InternationalBioinformaticsEnzymatic-Reactions Slots

EnzymeReactionCofactorsProsthetic-GroupsAlternative-Substrates

SRI InternationalBioinformaticsPathways Slots

Reaction-ListPredecessorsPrimaries

SRI InternationalBioinformaticsInspecting PGDB Instance

Frames

Right-click on object handles to find frame-idShow menu allows printing of frames

SRI InternationalBioinformaticsInspecting 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: http://www.ai.sri.com/~gkb/user-man.html Publication: http://www.ai.sri.com/pkarp/pubs/97gkb.ps