Cell Ontology Meeting, Jackson Labs May 2010 David Osumi-Sutherland.

Cell Ontology Meeting, Jackson Labs May 2010

David Osumi-Sutherland

Cell types in the Drosophila anatomy ontology

• class: defined/total– cell: 921/3089• neuron: 715/1383

– interneuron: 84/382– sensory neuron: 432/649– motor neuron: 107/194 (many more to add)– neurosecretory neuron 26/26

• glial cell: 5/96• ganglion mother cell: 23/23 (many more to add)• neuroblast: 23/264

Context dependent cell classification

• Many useful classifications of cells depend on their relation to other cells, tissues or the organism they are present in:

Tissue context

All epithelial cells are tightly connected to other epithelial cells to form a sheet that is a semi-permeable barrier.

Organismal context

– A neuroendocrine cell is a neuron that secretes an endocrine hormone. • An endocrine hormone is a

hormone that is carried throughout the body by the circulatory system

Roles

• Depending on context, the same secreted molecule might be:– a neurotransmitter• acts at synapse

– a paracrine hormone• acts locally

– an endocrine hormone• released into circulatory system

Context in the nervous system

• A (primary) motor neuron must be synapsed to a muscle and capable of contributing to stimulating contraction of that muscle.

cell body

LHLateral Horn

iACT

MBc

Mushroom Body calyx

antennal lobe

dendrite

axon

innervation MBc & LH

terminal arbour of dendrite fillsglomerulus DL1, receives synapses

glomerulus

We thank Greg Jefferies for kindly allowing us to use this image.

DL1 adPN adPN

• DL1 adPN: ”A uniglomerular antennal lobe projection neuron, with a soma in the AL cortex from the ad neuroblast lineage (embryonic born) whose dendrites innervate only antennal lobe glomerulus DL1 and whose axon fasciculates with the iACT and innervates the mushroom body calyx (via a collateral) and the lateral horn.”

• SubClassOf: develops_from some ‘ad neuroblast’

• adPN: “An antennal lobe projection neuron of the ad neuroblast lineage.” • EquivalentTo: ‘antennal lobe projection neuron’ that develops_from some ‘ad

neuroblast’

neural cell types in context- an example

part vs overlap

r1r1 r2r2rr1 overlaps r2 iff ::for some r , r part_of r1 and r part_of r2.non-transitive

yy

x

y part_of xtransitive

has_soma_location

• N has_soma_location some R – Description:

• Relation between a neuron and an anatomical structure in which its soma is located.

– Expands to:N1 SubclassOf (

has_part some (‘soma ; GO:’ that part_of some R

)

domain: neuron; range: anatomical entitySubPropertyOf: overlaps(Or use property chain: has_part o part_of -> overlaps ?)

Chemical synapsing

Properties for capturing chemical synapsing between neuron classes can be defined structurally based on what the pre and post synaptic membranes are part of

pre-synaptic membrane

post-synaptic membrane

synapsed_to

• N1 synapsed_to some N2 – Description: • Relation between a neuron and an anatomical

structure it forms a chemical synapse to.

– Expands to:N1 SubclassOf (

has_part some (‘pre-synaptic membrane ; GO:0042734’ that part_of some (

‘synapse ; GO:0045202’ that has_part some (‘post-synaptic membrane ; GO:0045211’ that

part_of some N2))))

domain: neuron; range: cell (?)

cell body

LHLateral Horn

iACT

MBc

Mushroom Body calyx

antennal lobe

dendrite

axon

innervation MBc & LH

terminal arbour of dendrite fillsglomerulus DL1, receives synapses

glomerulus

We thank Greg Jefferies for kindly allowing us to use this image.

DL1 adPN adPN

Where are the synapses ?To capture this we need relations between neurons and the anatomical structures they form synapses in.

neural cell types in context- an example

synapses_in• N synapses_in R• Description: relation between a neuron and some

structure it forms synapses in.• expands_to: N SubClassOf (

has_part some (‘pre-synaptic membrane ; GO:0042734’ that part_of some (

‘synapse ; GO:0045202’ that part_of some R)))

• domain: neuron; range: anatomical entity

• Note: – If N synapses_in R1 and R1 part_of R2 then N synapses_in R2.

• Can express this as property chain:– synapses_in o part_of -> synapases_in

axon_synapses_in• N axon_synapses_in R• Description: relation between a neuron and some structure

its axon forms synapses in.• expands_to: N SubClassOf (

has_part some (‘axon ; GO:0030424’ that has_part some (

‘pre-synaptic membrane ; GO:0042734’ that part_of some (‘synapse ; GO:0045202’ that part_of some R

))))• domain: neuron; range: anatomical entity

• Note: – If N axon_synapses_in R1 and R1 part_of R2 then N axon_synapses_in R2.

• Can express this as property chain:– axon_synapses_in o part_of -> axon_synapases_in

cell body

LHLateral Horn

iACT

MBc

Mushroom Body calyx

antennal lobe

dendrite

axon

innervation MBc & LH

terminal arbour of dendrite fillsglomerulus DL1, receives synapses

glomerulus

We thank Greg Jefferies for kindly allowing us to use this image.

DL1 adPN adPN

‘DL1 adPN’ axon_synapses_in some ‘lateral horn’‘DL1 adPN’ axon_synapses_in some ‘mushroom body calyx’

Reasoning:‘mushroom body calyx’ part_of some mushroom bodytherefore ‘DL1 adPN’ axon_synapses_in some ‘mushroom body’

neural cell types in context- an example

synapsed_by

• N1 synapsed_by some N2 – Description: • Relation between an anatomical structure and a

neuron that chemically synapses to it.– Expands to:

N1 SubclassOf (has_part some (

‘post-synaptic membrane ; GO:0045211’ that part_of some ( ‘synapse ; GO:0045202’ that has_part some (

‘pre-synaptic membrane ; GO:0042734’ that part_of some N2))))

domain: cell (?); range: neuron

synapsed_in• N1 synapsed_in R• Description: relation between a neuron and some

structure it is synapsed in.• expands_to: N1 SubClassOf (

has_part some (‘post-synaptic membrane ; GO:0045211’ that part_of some

‘synapse ; GO:0045202’ that part_of some R)))

• domain: neuron; range: anatomical entity

• Note:– If N1 synapsed_in R1 and R1 part_of R2 then synapsed_in R2.

• Can express this as property chain:– synapsed_in o part_of -> synapased_in

dendrite_synapsed_in• N1 dendrite_synapsed_in R• Description: relation between a neuron and some structure

its axon forms synapses in.• expands_to: N1 SubClassOf (

has_part some (‘dendrite; GO:0030425’ that has_part some (‘pre-synaptic membrane ; GO:0042734’ that part_of some (

‘synapse ; GO:0045202’ that part_of some R)))

• domain: neuron; range: anatomical entity

• Note:– If N1 dendrite_synapsed_in R1 and R1 part_of R2 then N1 dendrite_synapsed_in

R2. • Can express this as property chain:

– dendrite_synapsed_in o part_of -> dendrite_synapsed_in

cell body

LHLateral Horn

iACT

MBc

Mushroom Body calyx

antennal lobe

dendrite

axon

innervation MBc & LH

terminal arbour of dendrite fillsglomerulus DL1, receives synapses

glomerulus

We thank Greg Jefferies for kindly allowing us to use this image.

DL1 adPN adPN

DL1 adPN dendrite_synapsed_in some glomerulus DL1

neural cell types in context- an example

synapse_in

• We don’t always know the direction of synapses, so a general relation is useful:

• synapse_in<- sub_property_of synapsed_in

<- sub_property_of dendrite_synapsed_in <- sub_property_of synapses_in

<- sub_property_of axon_synapses_in

But how does this fit with expansion?

fasciculates_in

• Description:– relationship between a neuron and a neuron projection bundle

(e.g.- tract or nerve bundle) that one or more of its projections travels through.

• instance level definition:– x fasciculates_with y iff: for some ‘neuron projection’ (np), np

part_of x and np overlaps y and np aligned_with y• SubPropertyOf: overlaps• domain: neuron; range: neuron projection bundle

• Note– As we need to say two things about the relation of np to y, we

can't use the class level expansion system to capture this.

cell body

LHLateral Horn

iACT

MBc

Mushroom Body calyx

antennal lobe

dendrite

axon

innervation MBc & LH

terminal arbour of dendrite fillsglomerulus DL1, receives synapses

glomerulus

We thank Greg Jefferies for kindly allowing us to use this image.

DL1 adPN adPN

DL1 adPN fasciculates_in some iACT

neural cell types in context- an example

Recording function

• We have no function ontology

• But we do have a great biological process ontology from GO

• =>• We need one or more relations that allow us

to define cell function using terms for the process that is the realization of that function.

Sensory function

• Drosophila anatomy ontology has 650 cell types defined, in part, using a GO sensory process term.

– e.g.- olfactory receptor neuron:• EquivalentTo: (neuron that has_function_in some

‘detection of chemical stimulus involved in sensory perception of smell’).

Recording Function in specific behaviors

• Some examples:– giant fiber neuron has_function_in some ‘jump

response’– gravity sensitive Johnston organ neuron’

has_function_in some ‘gravitaxis’

Distinct relation needed for these vs process intrinsic to cell?

releases_neurotransmitter

• Options: – 1. Define new relation referencing

‘neurotransmitter release ; GO:0007269’• The regulated release of neurotransmitter into the

synaptic cleft.

– 2. Work with GO to get terms for release of specific neurotransmitters and use has_function_in

Upper ontology of neurons ?

• neuron SubClassOf (capable_of action potential propagation)– sensory neuron EquivalentTo (neuron and

has_function some ‘detection of stimulus involved in sensory perception)

– motor neuron: SubClassOf (synapsed_to some muscle)

– interneuron• local interneuron• projection neuron

– endocrine neuron