PATOAn ontology for phenotypes.

The development of PATO is the work of George Gkoutos, supported by the NCBO, working in Cambridge.

Phenotype And Trait Ontology (PATO)

• Phenotypes may be described in many different dimensions, e.g.– the biochemical ('alcohol dehydrogenase null')– the cellular ('cell division arrested at metaphase'), – the anatomical ('eye absent')– the behavioral (‘hyperactive’). – etc.

• In whatever dimension and granularity, however, there is a commonality and the great majority of, if not all, phenotypic descriptions can be decomposed into two parts

– An entity that is affected. This entity may be an enzyme, an

anatomical structure or a complex biological process.– The qualities of that entity.

Features of Qualities

• Qualities are the basic properties that we can perceive and/or measure:– colors, sizes, masses, lengths etc.

• Qualities inhere to entities: every entity has certain qualities, which exist as long as that entity exists.

• Qualities belong in a finite set of quality types (i.e. color, size etc) and inhere in specific individuals. Each quality is constantly dependent on the entity it inheres in.

PATO’s Top level divisions

PATO’s hierarchical organisation • At lower levels PATO is organized by the nature of the

qualities:

– Physical qualities, such as mass, velocity and color; – Cellular qualities, such as ploidy (which inhere in a cell or

cell nucleus by virtue of the number of chromosomes it has) and cellular potential (capability of differentiating into other cell types);

– Organismal qualities, such as behavioral qualities.

• The leaf nodes of PATO represent specific qualities, such as “orange” (a kind of color), “concave” (a kind of shape) and “increased length” (a kind of size).

Phenotypic Character

(mouse body weight) (mouse anatomy: body + PATO: weight)

(Drosophila anatomy: eye + PATO: color)

(ChEBI: glucose + PATO: concentration)

(eye colour)(glucose concentration)

Phenotypic Character entity + quality

increased size [of a] hepatocellular carcinoma

hepatocellular carcinoma (MPATH:357) has_quality increased size (PATO:0000586)

Assay (eg. Histopathology, blood chemistry) {constrained_by}

| (environmental & genetic)- {of type} - conditions

Entity (eg. MA) - Quality (PATO)Entity (eg.MPATH) - Quality (PATO) Entity (eg. Cell) - Quality (PATO)

{

Representation of Phenotypic data

Measurements

• PATO – part of a representation of qualitative phenotypic information

• More often than not it is important to record quantitative information that results from a specific measurement of a quality

The tail of my mouse is 2.1 cm

PATO & measurements

• Measurements involve units (Phenotypic Character + Unit)

• UO – an ontology of units– UO’s top-level division is between primary base units

of a particular measure and units that are derived from base units

– mapping between the various scalar qualities (such as weight, height, concentration etc.) and the corresponding units used to measure those qualities

Mapping PATO to the UO

PATO Annotations

• Descriptions can be pre- or post- composed• Post-coordinated

EQ methodologyPATO + Entity (quality bearer)

Entity = GO, AOs, Cell, etc.

–NCBO fly-fish-human disease gene annotations–BIRN image annotation (neurodegenerative disease)–NESCent / AToL - evolutionary character matrices–…

• Pre-coordinated–MGI Mouse genotype-phenotype annotation (Mammalian Phenotype)–Gramene trait annotation (Plant Trait Ontology)–Worm–…

Reconciling pre and post composed annotations

• Retrospective PATO definitions of pre-coordinated terms in phenotype ontology

• Precomposed Ontologies– Mammalian Phenotype– Plant trait– Worm phenotype – etc.

• OMIM

EQ definitions

Aristotelian definitions (genus-differentia)

A <Q> *which* inheres_in an <E>

[Term] id: MP:0001262 name: decreased body weightnamespace: mammalian_phenotype_xpSynonym: low body weightSynonym: reduced body weightdef: " lower than normal average weight “[] is_a: MP:0001259 ! abnormal body weightintersection_of: PATO:0000583 ! decreased weightintersection_of: MA:0002405 ! adult mouse

Some examples

Example 1

• MP:0000350 – abnormal cell proliferation– MP:0000352 - decreased cell proliferation – ..

• WBPhenotype0000171 – cell_proliferation_abnormal– WBPhenotype0000171 – cell_proliferation_reduced– ..

[Term]id: WBPhenotype0000171 ! cell_proliferation_abnormalIntersection_of: PATO:0000460 ! abnormalIntersection_of: inheres_in GO:0008283 ! cell proliferation

[Term]id: WBPhenotype0000171 ! cell_proliferation_reducedIntersection_of: PATO:0000468 ! decreasedIntersection_of: inheres_in GO:0008283 ! cell proliferation

[Term]id: MP:0000350 ! abnormal cell proliferation Intersection_of: PATO:0000460 ! abnormalIntersection_of: inheres_in GO:0008283 ! cell proliferation

[Term]id: MP:0000350 ! decreased cell proliferation Intersection_of: PATO:0000468 ! decreasedIntersection_of: inheres_in GO:0008283 ! cell proliferation

Example 2MP, WBPhenotype, OMIM etc.

• MP:0001265 – decreased body size– MP:0001255 – decreased body height

• WBPhenotype0000229 – small

• OMIM %210710 – short stature

[Term]id: MP:0001265 ! decreased body sizeintersection_of: PATO:0000587 ! decreased sizeintersection_of: inheres_in MA:0002405 ! adult mouse

[Term]id: MP:0001255 ! decreased body heightintersection_of: PATO:0000569 ! decreased heightintersection_of: inheres_in MA:0002405 ! adult mouse

[Term]id: WBPhenotype0000229 ! smallintersection_of: PATO:0000587 ! decreased sizeintersection_of: OBO_REL:inheres_in WBls:0000041 ! Adult

[Term]id: OMIM:xxxxxxx ! short stature intersection_of: PATO:0000587 ! decreased sizeintersection_of: OBO_REL:inheres_in FMA!:20394 ! Body

[Term]id: OMIM:xxxxxxx ! short stature intersection_of: ATO:0000569 ! decreased heightintersection_of: OBO_REL:inheres_in FMA:20394 ! Body

Assay Controlled Vocabulary

• Abnormality• Relative_to• Ranges of values• Allows the schema to be dynamic

• Definition of qualities and their relations• Explicit differences (between laboratories)• Allows labs around the world to “plug-in” theirassays to the schema

Assay

Phenotypic Character

Phenotypic Character

Phenotypic Character