PATO An 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: )

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 methodology PATO + 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 *which* inheres_in an [Term] id: MP: name: decreased body weight namespace: mammalian_phenotype_xp Synonym: low body weight Synonym: reduced body weight def: " lower than normal average weight “[] is_a: MP: ! abnormal body weight intersection_of: PATO: ! decreased weight intersection_of: MA: ! adult mouse

Some examples

Example 1 MP: – abnormal cell proliferation – MP: decreased cell proliferation –.. WBPhenotype – cell_proliferation_abnormal – WBPhenotype – cell_proliferation_reduced –..

[Term] id: WBPhenotype ! cell_proliferation_abnormal Intersection_of: PATO: ! abnormal Intersection_of: inheres_in GO: ! cell proliferation [Term] id: WBPhenotype ! cell_proliferation_reduced Intersection_of: PATO: ! decreased Intersection_of: inheres_in GO: ! cell proliferation [Term] id: MP: ! abnormal cell proliferation Intersection_of: PATO: ! abnormal Intersection_of: inheres_in GO: ! cell proliferation [Term] id: MP: ! decreased cell proliferation Intersection_of: PATO: ! decreased Intersection_of: inheres_in GO: ! cell proliferation

Example 2 MP, WBPhenotype, OMIM etc. MP: – decreased body size – MP: – decreased body height WBPhenotype – small OMIM % – short stature

[Term] id: MP: ! decreased body size intersection_of: PATO: ! decreased size intersection_of: inheres_in MA: ! adult mouse [Term] id: MP: ! decreased body height intersection_of: PATO: ! decreased height intersection_of: inheres_in MA: ! adult mouse [Term] id: WBPhenotype ! small intersection_of: PATO: ! decreased size intersection_of: OBO_REL:inheres_in WBls: ! Adult [Term] id: OMIM:xxxxxxx ! short stature intersection_of: PATO: ! decreased size intersection_of: OBO_REL:inheres_in FMA!:20394 ! Body [Term] id: OMIM:xxxxxxx ! short stature intersection_of: ATO: ! decreased height intersection_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” their assays to the schema Assay Phenotypic Character Phenotypic Character Phenotypic Character