representing development david osumi-sutherland – flybase fabian neuhaus - national institute of...

Representing Development

David Osumi-Sutherland – FlyBase

Fabian Neuhaus - National Institute of Standards and Technology

Stage

Campos-Ortega and Hartenstein, 1997

VNE = Ventral neurectoderm

Neuroblast delamination from the ventral neurectoderm

Neuroblast

ganglion mother cell

Ventral neurectodermcells

{Ventral Neurectoderm

(VNE)

Figure from Doe, 1992, Development:116

Stage

ventral nerve cord primordium

(ganglion mother cell)


Stage

ventral nerve cord primordium


late stage 8 stage 10

early ES10

late stage 11

Neuroblast delamination from VNE to VNC primordium

Each circle is a specific neuroblast (NB) typeColours denote gene expression

Figure from Doe, 1992, Development:116

Development of U2 neuron

U2 neuronGMC 7-1b

during stage 12

NB7-1VNE

during stage 8 during stage 9

VNC prim VNC

during stage 17develops_from

part

Stage specific part relations such as these cannot be recorded using standard OBO relations

Limitations of current system

ES8 ES9 ES10 ES11 ES12

GMC

VNC prim

GMC 7-1bis_a

part part

ganglion mother cell GMC 7-1b neuroblast NB 7-1develops_from neuroblast NB7-1 is_a neuroblastis_a ganglion mother cell (GMC)

NB7-1

develops_from

Needed – system to connect anatomy to stage

Needed – system for capturing thesestage specific part relations

time

ES = embryonic stage

What is developmental time?

In any developmental process, (e.g.- development of a whole organism) many events happen in an invariant order.

These events can be used as markers of developmental progress or time. This is the basis of many standard stage series.

These marker events can be the birth, death, or transformation an anatomical structure. the beginning, end and key point in a developmental processes

System for ordering events

Events are treated as instants – they have no time dimension.

There are only 2 types of timing relationships between event instances (e, f):

e before f (<)

e simultaneous f (≈)

both can be derived from

before_or_simultaneous_ with (≤) :

definition: e<f := e≤f AND NOT f≤e

definition: e≈f := e≤f AND f≤e

x

p

α(x) ω(x)ω(p)α(q)

Timing relations between instances of occurrents, continuants

Events:α(p) - beginning of pω(p) - end of an paxiom: α(o) before ω(o)Time

x starts_during p := (α(p) before α(x)) AND (α(x) before ω(p))

q

α(p) ω(q)

Reference Processes

The invariability of the order of two events is always relative to some reference process: X before Y during oogenesis many instances of oogenesis occur in parallel in an

adult female, but with no shared starting time so, relative to the life of an adult female, X and Y

have no invariant order.

Drosophila Oogenesis

Ternary relations ?

Reference processes could be recorded using ternary relations (A before B during C...)

But these are not supported in OWL or OBO, or by their respective editing tools – Protege and OBO-Edit.

How to avoid using ternary relations

For each type for which timing is to be captured – record a reference occurrent.

A reference_occurrent B := all Continuant or Occurrent types have only one

reference process. all occurrents occur only once during their

reference process if Aa is an occurrant, then a part_of

(ref_occurrant(a)) if Aa is a continuant, then a participates_in

(ref_occurrant(a))

referenceoccurrent(x, y) -> (Universal(x) & is_a(y,Occurrent)).

referenceoccurrent(x, y) & referenceoccurrent(x, z) -> (y =z).

referenceoccurrent(x, y) & is_a(x,Occurrent) ->

all x1 (I(x, x1) ->

(I(y, refoccurrent(x1))

& ilo_part(x1,refoccurrent(x1))

& all y1 (I(y,y1) & ilo_part(x1, y1) -> (y1 = refoccurrent(x1)))

)).

referenceoccurrent(x, y) & is_a(x,Continuant) ->

all x1 (I(x, x1) ->

(I(y, refoccurrent(x1))

& participates_in(x1,refoccurrent(x1))

& all y1 (I(y,y1) & participates_in(x1, y1) -> (y1 = refoccurrent(x1)))

)).

Division of reference process into a reference scale

ES7 ES8 ES9 ES10

time

ES6

cellular-ization

stomodeal invaginationgastrulation

germ band extension TP invagination

Stage

Unique Process

gastrulation reference_occurrent embryogenesis

embryonic stage 5 reference_occurrent embryogenesis

gastrulation begins_at_end_of embryonic stage 5

stomodeal invagination begins_at_end_of embryonic stage 9

ES5

begins_at_end_of – formal def

O begins_at_end_of P

↔ (O is_a Occurrent

& P is_a Occurrent

& o (O(o)∀

→ ∃ p (P(p)

& refoccurrent(o) = refoccurrent(p)

&(omega(p) ≈ alpha(o)))))

List of type level relations - 1

unique*1 Occurrent to unique Occurrent begins_at_end_of begins_during ends_during begins_before ends_after simultaneous_with * happens_during **1 Unique here means, happens only once during reference process

*2 non-essential but reduces number of relationships needed


GMC first_exists_during embryonic stage 8 (ES8):some instance of GMC starts to exist during* all instances of ES8 ANDAll instances of GMC (start to exist during* ES8 OR start to exist after the end of some instance of ES8)

*during is shorthand for 'the start of X is after the start of Y and before the end of Y'

GMC

DAG – graph-viewomitting timing relationships

Timing relations between types

Time

is_a inheritance of timing


GMCGMC 7-1bis_a

ganglion mother cell (GMC)first_exists_during embryonic stage 8 (ES8)ganglion mother cell GMC 7-1ball_begin_to_exist_during embryonic stage 9 (ES9)all_cease_to_exist_during embryonic stage 12 (ES12)is_a ganglion mother cell (GMC)


all_begin_to_exist_during – formal definition

C all_begin_to_exist_during O

↔ (C is_a Continuant

& O is_a Occurrent

& c t ( C (c,t)∀ ∀

→ ∃ o

( O(o)

& refoccurrent(c) = refoccurrent(o)

& (alpha(o) ≤ alpha(c))

& (alpha(c) ≤ omega(o)))))

List of type level timing relations - 2 unique*1 occurrent to non-unique continuant:

first_exists_during last_exists_during all_begin_to_exist_during *2

all_cease_to_exist_during *2

begins_to_exist_at_end_of begins_to_exist_after ceases_to_exist_before exists_only_during *2

*1 Unique here means, happens only once during reference process

*2 non-essential but reduced number of relationships needed


GMC

VNC prim

GMC 7-1bis_a

part* part*

We can’t record has_part here

Y has_part X: some X part_of all Y, no matter what stage.



VNC prim

U2 neuron

VNC

develops_from

time

ES12

part* part*

We can’t record part_of here

FALSE:Y part_of X: all U2 neuron part_of some VNC prim, for all stages that U2 neuron exists

Solution to the part problem:time_restricted_integral_part_of

(tri_part_of)

For any time point where some instance of X and some

instance of Y exist:

All instances of X part_of some instance of Y

AND

Some instance of X part_of all instances of Y

time_restricted_integral_part_of(C tr_part_of D)


& D is_a Continuant

& ∀c ∀t (C (c, t)

→ ∃d (∃t₁ D( d, t₁) &(c part_of d at t₁)) &

∀t₂ ((c exists_at t₂) & (d exists_at t₂) →(c part_of d at t₂))))).

( C tr_has_part D)


& D is_a Continuant

& ∀c ∀t (C (c, t)

→ ∃d (∃t₁ D( d, t₁) &(d part_of c at t₁)) &

∀t₂ ((c exists_at t₂) & (d exists_at t₂) →(d part_of c at t₂))))).

C tr_integral_part_of D ↔ (C tr_part_of D & D tr_has_part C )


GMC

VNC prim

GMC 7-1bis_a

tdi_part_ofDAG – graph-viewomitting timing relationships

tdi_part_of

NB7-1

develops_from

ganglion mother cell (GMC)first_exists_during embryonic stage 8 (ES8)tdi_part_of ventral nerve cord primordium (VNC prim)ganglion mother cell GMC 7-1bdevelops_from neuroblast NB7-1all_begin_to_exist_during embryonic stage 9 (ES9)all_cease_to_exist_during embryonic stage 9 (ES9)tdi_part_of ventral nerve cord primordium (VNC prim)


VNC prim

U2 neuron

U2 neurondevelops_from ganglion mother cell GMC 7-1bis_a motor neurontdi_part_of ventral nerve cord primordiumtdi_part_of ventral nerve cordall_begin_to_exist_during embryonic stage 13 (ES13)

GMC 7-1b

develops_from

VNC

tdi_part_oftdi_part_of

develops_from

time

ES12

representing development david osumi-sutherland – flybase fabian neuhaus - national institute of...

Documents

reference occurrent

vneduring stage

y referenceoccurrentx

y1 y1

vnc primvncduring stage

standard stage series

y universalx

developmental time