Outline

1
Outline

• Current RO realization
• Identifier policy
• Class and instance relations and RO
• RO and the BFO upper ontology
• RO Tracker and new relation process
• Use cases for new relations
• GO and Phenotype

2
Current realization of the RO

• Initial realization was ro.pdf
• Current primary realization is ro.obo
• Automatically translated to ro.owl
• Obo2owl mapping
• There are other unofficial translations
• E.g. BRO

3
Anatomy of a RO term
Typedef id OBO_RELpart_of name part_of def
"For continuants C part_of C' if and only if
given any c that instantiates C at a time t,
there is some c' such that c' instantiates C' at
time t, and c part_of c' at t. For processes P
part_of P' if and only if given any p that
instantiates P, there is some p' such that p'
instantiates P', and p part_of p'. (Here
part_of is the instance-level part-relation.)"
PMID15892874 comment Parthood as a relation
between instances The primitive instance-level
relation p part_of p1 is illustrated in
assertions such as this instance of rhodopsin
mediated phototransduction part_of this instance
of visual perception. This relation satisfies
at least the following standard axioms of
mereology reflexivity (for all p, p part_of p)
anti-symmetry (for all p, p1, if p part_of p1 and
p1 part_of p then p and p1 are identical) and
transitivity (for all p, p1, p2, if p part_of p1
and p1 part_of p2, then p part_of p2). Analogous
axioms hold also for parthood as a relation
between spatial regions. For parthood as a
relation between continuants, these axioms need
to be modified to take account of the
incorporation of a temporal argument. Thus for
example the axiom of transitivity for continuants
will assert that if c part_of c1 at t and c1
part_of c2 at t, then also c part_of c2 at t.
Parthood as a relation between classes To define
part_of as a relation between classes we again
need to distinguish the two cases of continuants
and processes, even though the explicit reference
to instants of time now falls away. For
continuants, we have C part_of C1 if and only if
any instance of C at any time is an
instance-level part of some instance of C1 at
that time, as for example in cell nucleus part_
of cell. inverse_of OBO_RELhas_part is_reflexive
true is_anti_symmetric true is_transitive true
4
Identifiers (non-numeric)
Typedef id OBO_RELpart_of name part_of def
"For continuants C part_of C' if and only if
given any c that instantiates C at a time t,
there is some c' such that c' instantiates C' at
time t, and c part_of c' at t. For processes P
part_of P' if and only if given any p that
instantiates P, there is some p' such that p'
instantiates P', and p part_of p'. (Here
part_of is the instance-level part-relation.)"
PMID15892874 comment Parthood as a relation
between instances The primitive instance-level
relation p part_of p1 is illustrated in
assertions such as this instance of rhodopsin
mediated phototransduction part_of this instance
of visual perception. This relation satisfies
at least the following standard axioms of
mereology reflexivity (for all p, p part_of p)
anti-symmetry (for all p, p1, if p part_of p1 and
p1 part_of p then p and p1 are identical) and
transitivity (for all p, p1, p2, if p part_of p1
and p1 part_of p2, then p part_of p2). Analogous
axioms hold also for parthood as a relation
between spatial regions. For parthood as a
relation between continuants, these axioms need
to be modified to take account of the
incorporation of a temporal argument. Thus for
example the axiom of transitivity for continuants
will assert that if c part_of c1 at t and c1
part_of c2 at t, then also c part_of c2 at t.
Parthood as a relation between classes To define
part_of as a relation between classes we again
need to distinguish the two cases of continuants
and processes, even though the explicit reference
to instants of time now falls away. For
continuants, we have C part_of C1 if and only if
any instance of C at any time is an
instance-level part of some instance of C1 at
that time, as for example in cell nucleus part_
of cell. inverse_of OBO_RELhas_part is_reflexive
true is_anti_symmetric true is_transitive true
5
Numeric IDs in RO v1.01
Typedef id OBO_RELpart_of alt_id
OBO_REL0000002 name part_of def "For
continuants C part_of C' if and only if given
any c that instantiates C at a time t, there is
some c' such that c' instantiates C' at time t,
and c part_of c' at t. For processes P part_of
P' if and only if given any p that instantiates
P, there is some p' such that p' instantiates P',
and p part_of p'. (Here part_of is the
instance-level part-relation.)"
PMID15892874 comment Parthood as a relation
between instances The primitive instance-level
relation p part_of p1 is illustrated in
assertions such as this instance of rhodopsin
mediated phototransduction part_of this instance
of visual perception. This relation satisfies
at least the following standard axioms of
mereology reflexivity (for all p, p part_of p)
anti-symmetry (for all p, p1, if p part_of p1 and
p1 part_of p then p and p1 are identical) and
transitivity (for all p, p1, p2, if p part_of p1
and p1 part_of p2, then p part_of p2). Analogous
axioms hold also for parthood as a relation
between spatial regions. For parthood as a
relation between continuants, these axioms need
to be modified to take account of the
incorporation of a temporal argument. Thus for
example the axiom of transitivity for continuants
will assert that if c part_of c1 at t and c1
part_of c2 at t, then also c part_of c2 at t.
Parthood as a relation between classes To define
part_of as a relation between classes we again
need to distinguish the two cases of continuants
and processes, even though the explicit reference
to instants of time now falls away. For
continuants, we have C part_of C1 if and only if
any instance of C at any time is an
instance-level part of some instance of C1 at
that time, as for example in cell nucleus part_
of cell. inverse_of OBO_RELhas_part is_reflexive
true is_anti_symmetric true is_transitive true
6
Text definitions
Typedef id OBO_RELpart_of name part_of def
"For continuants C part_of C' if and only if
given any c that instantiates C at a time t,
there is some c' such that c' instantiates C' at
time t, and c part_of c' at t. For processes P
part_of P' if and only if given any p that
instantiates P, there is some p' such that p'
instantiates P', and p part_of p'. (Here
part_of is the instance-level part-relation.)"
PMID15892874 comment Parthood as a relation
between instances The primitive instance-level
relation p part_of p1 is illustrated in
assertions such as this instance of rhodopsin
mediated phototransduction part_of this instance
of visual perception. This relation satisfies
at least the following standard axioms of
mereology reflexivity (for all p, p part_of p)
anti-symmetry (for all p, p1, if p part_of p1 and
p1 part_of p then p and p1 are identical) and
transitivity (for all p, p1, p2, if p part_of p1
and p1 part_of p2, then p part_of p2). Analogous
axioms hold also for parthood as a relation
between spatial regions. For parthood as a
relation between continuants, these axioms need
to be modified to take account of the
incorporation of a temporal argument. Thus for
example the axiom of transitivity for continuants
will assert that if c part_of c1 at t and c1
part_of c2 at t, then also c part_of c2 at t.
Parthood as a relation between classes To define
part_of as a relation between classes we again
need to distinguish the two cases of continuants
and processes, even though the explicit reference
to instants of time now falls away. For
continuants, we have C part_of C1 if and only if
any instance of C at any time is an
instance-level part of some instance of C1 at
that time, as for example in cell nucleus part_
of cell. inverse_of OBO_RELhas_part is_reflexive
true is_anti_symmetric true is_transitive true
7
Overloaded definitions
Typedef id OBO_RELpart_of name part_of def
"For continuants C part_of C' if and only if
given any c that instantiates C at a time t,
there is some c' such that c' instantiates C' at
time t, and c part_of c' at t. For processes P
part_of P' if and only if given any p that
instantiates P, there is some p' such that p'
instantiates P', and p part_of p'. (Here
part_of is the instance-level part-relation.)"
PMID15892874 comment Parthood as a relation
between instances The primitive instance-level
relation p part_of p1 is illustrated in
assertions such as this instance of rhodopsin
mediated phototransduction part_of this instance
of visual perception. This relation satisfies
at least the following standard axioms of
mereology reflexivity (for all p, p part_of p)
anti-symmetry (for all p, p1, if p part_of p1 and
p1 part_of p then p and p1 are identical) and
transitivity (for all p, p1, p2, if p part_of p1
and p1 part_of p2, then p part_of p2). Analogous
axioms hold also for parthood as a relation
between spatial regions. For parthood as a
relation between continuants, these axioms need
to be modified to take account of the
incorporation of a temporal argument. Thus for
example the axiom of transitivity for continuants
will assert that if c part_of c1 at t and c1
part_of c2 at t, then also c part_of c2 at t.
Parthood as a relation between classes To define
part_of as a relation between classes we again
need to distinguish the two cases of continuants
and processes, even though the explicit reference
to instants of time now falls away. For
continuants, we have C part_of C1 if and only if
any instance of C at any time is an
instance-level part of some instance of C1 at
that time, as for example in cell nucleus part_
of cell. inverse_of OBO_RELhas_part is_reflexive
true is_anti_symmetric true is_transitive true
Continuants
8
Overloaded definitions
Typedef id OBO_RELpart_of name part_of def
"For continuants C part_of C' if and only if
given any c that instantiates C at a time t,
there is some c' such that c' instantiates C' at
time t, and c part_of c' at t. For processes P
part_of P' if and only if given any p that
instantiates P, there is some p' such that p'
instantiates P', and p part_of p'. (Here
part_of is the instance-level part-relation.)"
PMID15892874 comment Parthood as a relation
between instances The primitive instance-level
relation p part_of p1 is illustrated in
assertions such as this instance of rhodopsin
mediated phototransduction part_of this instance
of visual perception. This relation satisfies
at least the following standard axioms of
mereology reflexivity (for all p, p part_of p)
anti-symmetry (for all p, p1, if p part_of p1 and
p1 part_of p then p and p1 are identical) and
transitivity (for all p, p1, p2, if p part_of p1
and p1 part_of p2, then p part_of p2). Analogous
axioms hold also for parthood as a relation
between spatial regions. For parthood as a
relation between continuants, these axioms need
to be modified to take account of the
incorporation of a temporal argument. Thus for
example the axiom of transitivity for continuants
will assert that if c part_of c1 at t and c1
part_of c2 at t, then also c part_of c2 at t.
Parthood as a relation between classes To define
part_of as a relation between classes we again
need to distinguish the two cases of continuants
and processes, even though the explicit reference
to instants of time now falls away. For
continuants, we have C part_of C1 if and only if
any instance of C at any time is an
instance-level part of some instance of C1 at
that time, as for example in cell nucleus part_
of cell. inverse_of OBO_RELhas_part is_reflexive
true is_anti_symmetric true is_transitive true
Processes
9
Implicit instance-level relations
Typedef id OBO_RELpart_of name part_of def
"For continuants C part_of C' if and only if
given any c that instantiates C at a time t,
there is some c' such that c' instantiates C' at
time t, and c part_of c' at t. For processes P
part_of P' if and only if given any p that
instantiates P, there is some p' such that p'
instantiates P', and p part_of p'. (Here
part_of is the instance-level part-relation.)"
PMID15892874 comment Parthood as a relation
between instances The primitive instance-level
relation p part_of p1 is illustrated in
assertions such as this instance of rhodopsin
mediated phototransduction part_of this instance
of visual perception. This relation satisfies
at least the following standard axioms of
mereology reflexivity (for all p, p part_of p)
anti-symmetry (for all p, p1, if p part_of p1 and
p1 part_of p then p and p1 are identical) and
transitivity (for all p, p1, p2, if p part_of p1
and p1 part_of p2, then p part_of p2). Analogous
axioms hold also for parthood as a relation
between spatial regions. For parthood as a
relation between continuants, these axioms need
to be modified to take account of the
incorporation of a temporal argument. Thus for
example the axiom of transitivity for continuants
will assert that if c part_of c1 at t and c1
part_of c2 at t, then also c part_of c2 at t.
Parthood as a relation between classes To define
part_of as a relation between classes we again
need to distinguish the two cases of continuants
and processes, even though the explicit reference
to instants of time now falls away. For
continuants, we have C part_of C1 if and only if
any instance of C at any time is an
instance-level part of some instance of C1 at
that time, as for example in cell nucleus part_
of cell. inverse_of OBO_RELhas_part is_reflexive
true is_anti_symmetric true is_transitive true
Instance-level
10
RO was developed as an ontology of relations
between types (classes)

• Defined in terms of instances
• pre-quantified
• X part_ofcls Y all X (at t) part_ofinst some Y
  (at t)
• Less flexible but easier to use
• This is how they are conceived of by their
  editors in most OBO ontologies
• And reflects how they are modeled in
  graph-oriented models
• OBO
• Most bioinformatics applications
• Model organism databases

11
Relations in OWL

• Class level relations (owlObjectProperties) do
  not make much sense in OWL (except subClassOf)
• post-quantified
• Each use of part_ofinst must be explicitly
  quantified
• E.g. heart ventricle subClassOf part_ofinst some
  heart
• We can use part_ofcls but this would be weird..
• OWL has no use for part_ofcls
• Benefits
• More flexibility
• E.g. ALL-SOME or ALL-ONLY cardinality
• Drawbacks
• Requires change of thinking for many ontology
  developers
• What do we do about quantification over time?

12
Implications for translation

• RO class level IDs correspond to URIs for OWL
  instance level properties
• OBO_RELpart_of
• gt
• http//purl.org/obo/owl/OBO_RELpart_of
• This is a little odd
• ALL-SOME Text definitions carried over to the owl
• This too is odd
• This has caused some confusion

13
3 alternative ways to fix this

• Abandon type level relations
• Reuse existing OBO IDs / URIs
• Rework text defs and relation props to be
  instance-level
• Introduce separate identifiers for instance and
  class level relations
• E.g. OBO_RELpart_of_some and OBO_RELpart_of
• Translate each OBO_RELpart_of_some use to
  quantified OBO_RELpart_of in OWL
• Clarify current punning semantics
• Use same ID, means different thing in different
  contexts (for OBO, graph models)
• Make it easier to excise class level info for owl

..or
..or
14
Long term what language for the primary
realization?

• OBOF
• OWL
• Common Logic
• http//obo.svn.sourceforge.net/viewvc/obo/obolog/t
  runk/

15
RO and the Basic Formal Ontology (BFO)

• BFO is an upper ontology of entities
• RO is an upper ontology of relations
• Current version relatively upper-ontology neutral
• Implicit references to continuants and processes
• There is a separate bridge resource
• ro_bfo_bridge
• Domain and range constraints
• Awkward to maintain
• BFO in owl with per-ontology versioned URIs
• RO in obo with OBO ID versioning policy

id OBO_RELhas_participant domain
spanOccurrent range snapContinuant
16
RO website

• Website
• http//obofoundry.org/ro
• RO 1-01 pre-release
• http//www.obofoundry.org/ro/pre/
• Resources
• obo owl realizations
• Wiki
• Mail list
• tracker

17
RO Tracker

• Standard sourceforge request tracker
• Link http//obofoundry.org/ro
• Different kinds of requests
• New term, obsoletion, change definition
• Anyone can submit a request
• Definitions preferred
• Requirements-oriented requests fine
• RO community can make comments on tracker or
  bring wider issues to list
• What happens after a request is made?

18
ro_proposed

• http//purl.org/obo/obo-all/ro_proposed/ro_propose
  d.obo.html
• Incubator for new relations
• 145 relations
• Caveat emptor
• Definitions of variable quality
• Definitions mature over time
• Can be copied to RO when ready
• Caveat emptor
• Used in
• OBO cross-products
• Pre and post coordinated
• Phenote and OBD

19
Relations required for XPs

• GO
• http//wiki.geneontology.org/index.php/Relationshi
  p_type_requirements
• Phenotype
• ltthis afternoongt

20
Relations for phenotypes
21
Relations for phenotypes

• Phenotypes are represented using dependent
  continuants
• Qualities
• Dispositions
• PATO is an ontology of qualities
• and dispositions. We think.
• and some things BFO may not consider qualities.
  More on that later.
• Phenotype descriptions can be pre or post composed

22
Quality instances and quality types

• Some examples of quality types
• Shape
• Sphericality
• Temperature
• Length
• Some examples of quality instances
• The shape of my head
• Your temperature
• The length of the tail of a particular mouse
  instance
• The unique redness instance of a particular fly
  eye

23
the type eye
the type red
instantiates
instantiates
the particular case of redness (of a
particular fly eye)
an instance of an eye (in a particular fly)
inheres in
24
Current uses

• Translating EQ model to logical representations
• Curator sees
• Entity FMAWall_of_eyeball
• Quality PATOthick
• Computer sees
• PATOthick
• THAT inheres_in FMAWall_of_eyeball
• Formalizing implicitly pre-coordinated ontologies
• 5000/8000 terms in mammalian phenotype defined
• Results can be combined and queried in
  ontology-aware databases
• OBD
• OWL-aware triplestore

25
The inheres_in relation
http//sourceforge.net/tracker/index.php?funcdeta
ilaid1748772group_id76834atid947684

• Instance level
• Primitive
• Time-indexed?
• Domain dependent continuant
• Range independent continuant
• Too restrictive?
• PATO has quality of a process
• Inverse bearer_of

• Type level
• All-some-all-times
• Q inh E
• Forall t, qQ exists eE, q inh e at t
• E bears Q
• Forall t, eE exists qQ, q inh e at t

26
PATO Top level division
Note some nodes omitted for brevity
Quality
Quality of a continuant A quality which
inheres In a continuant
Quality of an occurrent A quality which
inheres In a process or spatiotemporal region
physical quality
cellular quality
duration
morphology
rate
color
arrested
premature
delayed
density
shape
size
structure
27
Inherence hierarchy
bfo/1.0
inheres_in quality_of realized_by
function_of role_of disposition_of
dependent_continuant quality realizable
function role disposition
bfo/1.0
bearer_of has_quality has_realizable
has_function has_role has_disposition
dependent_continuant quality realizable
function role disposition
28
Inherence hierarchy
bfo/1.0
inheres_in quality_of realized_by
function_of role_of disposition_of
dependent_continuant quality realizable
function role disposition
bfo/1.0
bearer_of has_quality has_realizable
has_function has_role has_disposition
dependent_continuant quality realizable
function role disposition
29
Inherence hierarchy 1.1
bfo/1.1
inheres_in generically_inheres_in
specifically_inhres_in quality_of
realized_by function_of role_of
disposition_of
Dependent_continuant generically_dependent
specifically_dependent quality realizable
function role disposition
bfo/1.1
bearer_of generically_bearer_of
specifically_bearer_of has_quality
has_realizable has_function has_role
has_disposition
Dependent_continuant generically_dependent
specifically_dependent quality realizable
function role disposition
30
Multiple inherence

• Generically dependent continuants inhere in
  multiple entities
• e.g. book contents and physical copies
• Specifically dependent continuants always inhere
  in a single entity
• This is what we are concerned with in PATO
• Quality
• Disposition
• Enforced with cardinality restriction
• GDC inheres_in min 2 bfoEntity
• SDC inheres_in 1 bfoEntity

31
Monadic vs relational
quality of a continuant
Monadic quality of a C A quality of a C that
inheres solely in the bearer and does not require
another entity
Relational quality of a C A quality of a C that
requires another entity apart from its bearer to
exist


concentration (of)
Connected-ness (to)
Sensitivity (to)
Physical quality
Cellular quality
morphology
shape
size
structure
32
Relational qualities

• All qualities inhere in a single bearer
• Some qualities have additional dependence on
  other entities (but they do not inhere in these
  entities)
• (Sensitivity to red light) of an eye
• The quality inheres_in the eye
• With respect to (towards) red light
• (Concentration of glucose) in blood
• The quality inheres_in the blood
• With respect to (towards) glucose
• What do we call this relation?
• Current placeholder towards
• Different relations for different qualities
• Where does this fit in the relation hierarchy?

33
depends_on towards inheres_in
generically_inheres_in specifically_inhres_in
quality_of realized_by
function_of role_of disposition_of
Dependent_continuant generically_dependent
specifically_dependent quality realizable
function role disposition
34
Relations and relational qualities

• Many RQs in PATO look suspiciously like relations
• Do we need both?
• Eye sensitive_to red_light
• Philosophical difference
• Quality types are instantiated instances inhere
• Relations are not instantiated
• Pragmatic difference
• RQs obtain by degree
• We want to attribute reasons for the RQ
• E.g. geneX causes sensitivity_to Y

35
Heart rate

• In PATO rates are qualities of processes
• BFO does not admit these are qualities
• What are they?
• Relational quality
• E.g. rate that inheres_in heart towards beating

36
Parts and absence

• PATO v0.1 allowed the following
• E wing Q patoabsent
• Recommended pattern
• E thorax Q (patolacking_part towards wing)
• Why not
• Thorax that lacks_part wing
• Or
• Thorax that has_part 0 wing owl

37
Multiple parts and granularity

• Vacuolated
• Monadic quality
• Has_part vacuole, in large quantities
• We can also use a relational quality
• Has_multiple_parts
• towards vacuole
• Or a relation?
• has_grain vacuole

38
Magnitude and measurements

• Some qualities are magnitudinal / scalar
• There exists in reality a total order over
  instances of the same type (at any given time)
• E.g.
• tail-lengthA_at_t1 lt tail-lengthB_at_t1 lt
  finger-lengthC_at_t1
• We only have epistemological access via
  measurements
• The measurement is not the phenotype
• Inaccuracy, error. Partial order
• Interval calculus
• Can simplify to total order for many applications

39
Magnitude relations

• Relative magnitude
• increased_relative_to (gt)
• decreased_relative_to (lt)
• Time-indexed instance level relation
• Degenerate/redundant hierarchy
• E.g.
• c1 taller_than c2 _at_ t ltgt
• c1 has_quality q1, q1 instance_of patoheight
• c2 has_quality q2, q2 instance_of patoheight
• q1 gt q2 _at_ t
• Not required but may be useful for reporting, NLP
  etc

40
Magnitude and units

• PATO accompanied by UO
• unit_of relation
• Determinates and determinable
• Option 1
• q has_magnitude (number,unit) _at_ t
• Option 2
• q has_ltunitgt number _at_ t
• E.g.
• (lenth of tail123) has_cm 1.2

41
Magnitude relatum is often implicit

• PATO has
• Q
• increased_Q
• descreased_Q
• q instance_of (increased_Q relative_to
  q1,q2,..) def
• q instance_of Q and
• Forall q in q1 q gt q
• Background set often implicit, not always stated
• E.g. wild type healthy

42
Canonical relations abnormal

• Current placeholder relation
• has_qualifier

id MP0000217 ! abnormal white blood cell
number intersection_of PATO0000053 !
count intersection_of qualifier PATO0000460 !
abnormal intersection_of inheres_in CL0000738 !
leukocyte

• Q has_qualifier abnormal
• Q is_a increased_Q relative_to nq or
• Q is_a decreased_Q relative_to nq
• Where nq inheres_in normal/wildtype

43
Constructing phenotype descriptions

• Other relations used
• Part_of, has_part

44
Relating genes, genotypes, gene products to
phenotypes

• Colloquial implicated_in, correlated_with
• We want to make a stronger relation
• G influences P def
• Exists Disposition D
• D towards P
• D depends_on G

45
Intermediate layer

• Problem
• Users freak out when they see words like
  inheres_in
• And who can blame them
• Solution
• Use intermediate representation Lens
• E.g. EQ model
• But logical representation is leaky
• We need to standardize presentation layer
• E.g. user-friendly synonyms obol style grammars

46
Pheno Relation summary
Ontology Used in
inheres_in RO 1.01 MP-XP, annotations RTS?
quality_of RO 1.01
towards RO 1.01 MP-XP, annotations
ltmag Ro_proposed BIRN/phenote
gtmag Ro_proposed BIRN/phenote
has_qualifier Ro_proposed MP-XP, annotations
unit_of UO
taller_than etc -
influences Ro_proposed OBD

47
(No Transcript)
48
Spatial relations in GO CC (cellular_component)
49
Current GO CC

• Definitions are not computable
• Extended GO
• cellular_component_xp
• Optional additional layer
• Adds computable genus-differentia definitions
• Uses
• Part_of
• Has_part
• Surrounds
• Surrounded_by

50
Uses cases

• Detecting inconsistency in GO
• Example cytoplasmic chromosome
• Reasoner classifies mt chromosome here
• Not the intent
• Changed to cytosolic chromosome
• Spatial reasoning
• E.g. reactome