Download Introduction to Anatomy ontologies

An Introduction to Anatomy Ontologies
Phenotype RCN
Feb 23, 2012
Melissa Haendel
Setting the stage
1. Who are we? What do we need? Why
are we here?
2. What is an anatomy ontology?
3. What kinds of anatomy ontologies
exist?
4. How are anatomy ontologies used?
5. Anatomical evidence
Who are we?
Domain Experts:
Anatomists, comparative morphologists,
developmental biologists,
immunologists, neuroscientists, etc.
Engineers: have to
build tools that can
consume ontologies
and give the
Domain Experts the
right results
Domain experts: want to query
for gene expression and
phenotypes across species
Ontologists: have to be
able to interpret and
represent domain
knowledge
computationally
Engineers:
Our tool builders
Ontologists:
Biologists-gone-informatics,
computer scientists and logicians
We want to enable:
 Comparison of structures across different organisms, scales
 Standardization of anatomical vocabulary among and between
communities
 Integration of anatomical data across databases
 Query across large amount of data
 Automatic reasoning to infer related classes
 Error checking
 Annotation consistency
Therefore, we build ontologies that are intelligible to:
Engineers
Domain experts
Ontologists
Machines
Anatomical information retrieval from
text-based resources
OMIM Query
# Records
“large bone”
785
“enlarged bone”
156
“big bone”
16
“huge bones”
4
“massive bones”
28
“hyperplastic bones”
12
“hyperplastic bone”
40
“bone hyperplasia”
134
“increased bone growth”
612
Less than ideal.
Why build an anatomy ontology?
A simple example
Number of genes annotated to each of the following
brain parts in an ontology:
brain 20
hindbrain 15
part_of rhombomere 10
part_of
Query brain without ontology 20
Query brain with ontology 45
Ontologies can facilitate grouping and retrieval of data
There are many useful ways to
classify parts of organisms:
 its parts and their arrangement
 its relation to other structures
what is it: part of; connected to; adjacent to,
overlapping?
 its shape
 its function
 its developmental origins
 its species or clade
 its evolutionary history
Cajal 1915, “Accept the view that nothing in nature is useless, even from the human point of view.”
An ontology is a classification
appendage
wing
antenna
fore
wing
hind
wing
Relationships record classifications
too
‘leg’ SubClassOf part_of some thoracic segment
part_of some ‘thoracic
segment
wing
leg
Multiple inheritance is very hard to
manage by hand
It is difficult to keep track of multiple
classification chains to:
• ensure completeness;
• avoid redundancy;
• Incorrect inheritance of classification
criteria from a distant superclass
The knowledge in an ontology can make the
reasons for classification explicit
Any sense organ that functions in the
detection of smell is an olfactory sense organ
sense organ
olfactory
sense
organ
capable_of
some
detection of
smell
Classifying
sense organ
capable_of some
detection of smell
nose
nose
olfactory
sense
organ
sense organ
nose
capable_of
some
detection of
smell
Compositionality and avoiding asserted
multiple inheritance
Let the reasoner do the work!
We can logically define composed classes and create
complex definitions from simpler ones
 aka: building blocks, cross-products, logical definitions
Descriptions can be composed at any time
 Ontology construction time (pre-composition)
 Annotation time (post-composition)
Formal necessary and sufficient definitions + a
reasoner
 Automatic (and therefore manageable) classification
 Requires subtype classification, so apart from the root
term(s), no term should lack an is_a parent.
Example of a post-composed anatomical entity
Plasma membrane of spermatocyte
• Plasma membrane [GO CC]
• Spermatocyte [Cell Ontology]
Genus
Differentia
a plasma membrane which is part_of a spermatocyte
Gene Ontology
Basic Formal Ontology
Cell Ontology
Many perspectives, many ontologies
behavior
clinical disorders
reactions
proteins
cellular
processes
chemical entities
evolutionary
characters
nervous system
neural crest
cells
cell
anatomy
physiological processes
development
tissues
phenotypes
processes
gross
anatomy
What kinds of anatomy ontologies exist?
Species-centric and multi-species ontologies
Mouse
 MA (adult)
 EMAP / EMAPA (embryonic)
Human
 FMA (adult)
 EHDAA2 (CS1-CS20)
Amphibian
 AAO
 XAO
Fish
 ZFA (zebrafish)
 MFO (medaka)
 TAO (teleosts)
Nematode
 WBbt (c elegans)
Arthropod
 FBbt (Drosophila)
 TGMA (Mosquito)
 HAO (hymenoptera)
 Arthropod anatomy ontology
Plant ontology
Species neutral ontologies
CARO (common anatomy reference
ontology)
Uberon (cross-species anatomy)
vHOG (vertebrate homologous organs)
CL (cell ontology)
GO (gene ontology)
Phenotype ontologies
MP mammalian phenotype
HP human phenotype
WB worm phenotype
Species-centric ontologies
The Zebrafish Anatomy Ontology
Used to record gene expression and phenotypes at different stages of development
Ontologies built for one species will not
work for others
http://ccm.ucdavis.edu/bcancercd/22/mouse_figure.html
http://fme.biostr.washington.edu:8080/FME/index.html
Multi-species anatomy ontologies
The Plant Ontology
Seed plants
(Angiosperms and
Gymnosperms)
Pteridophytes
(Ferns and
Lycopods)
Bryophytes
(Mosses, Hornworts
and Liverworts)
Algae
Challenge is in representing diversity in anatomy, morphology, life cycles,
growth patterns
Bowman et al, Cell, 2007
Example of complexity arising from
multiple species-contexts
cell
nucleate cell
erythrocyte
enucleate
cell
not
applicable
in all
contexts
Example of complexity arising from
multiple species-contexts
cell
enucleate
cell
nucleate cell
species ontologies
attached at appropriate
level
CL:0000232
CL:0000562
nucleate
erythrocyte
ZFA:0009256
…
erythrocyte
…
zebrafish
nucleate
erythrocyte
CL:0000592
enucleate
erythrocyte
human
erythrocyte
FMA:81100
Using reasoners to detect errors
UBERON: bone
disjoint with
Drosophila melanogaster
part_of
only_in_taxon
is_a
is_a
Homo sapiens
UBERON: tibia
is_a
Fruit fly FBbt ‘tibia’
Vertebrata
✗
is_a
part_of
Human FMA ‘tibia’
Developmental Biology, Scott Gilbert, 6th ed.
The Gene Ontology has an anatomy ontology
zebrafish
Look ma, no pons!
human
Phenotype ontologies also have inherent anatomy
WBbt
C. elegans
phenotype
Designed primarily for annotation of phenotypes within a single species
Representing different levels of granularity
GO
lateral line
development
neuromast
development
?
hair cell
development
?
neuromast part_of lateral line
hair cell part_of neuromast
cilium
development
cilium part_of hair cell part_of neuromast
The problem: Data Silos
is_a (SubClassOf)
part_of
develops_from
surrounded_by
GO
FMA
multicellular
organismal process
EHDAA2
pharyngeal region
organ system
solid organ
respiratory
system
parenchymatous
organ
Lower
respiratory
tract
lobular organ
pleural sac
lung
respiratory gaseous
exchange
respiratory
primordium
respiratory system
process
lung bud
lung
MPO
abnormal respiratory
system morphology
MA
thoracic
cavity
organ system
thoracic
cavity organ
respiratory
system
abnormal lung
morphology
lung
abnormal pulmonary
acinus morphology
pulmonary
acinus
abnormal pulmonary
alveolus morphology
lung
alveolus
alveolar sac
How to synchronize anatomy
ontologies
Three approaches:
 Mapping
 Direct reconciliation
 Synchronization using
imports/MIREOT
There are issues with mappings
Class A
Class B
In Bioportal?
Useful?
FMA extensor
retinaculum of wrist
MA retina
Yes
No
FMA portion of blood
MA blood
No
Yes
ZFA Macula
MA macula
Yes
No
ZFA aortic arch
MA arch of aorta
Yes
Dubious
ZFA hypophysis
MA pitiuitary
No
Yes
FMA tibia
FBbt tibia
Yes
No
FMA colon
GAZ Colón, Panama
Yes
No
PATO male
Chebi maleate 2(-)
Yes
No
Reconciliation and linking between TAO and ZFA
Zebrafish terms are is_a subtypes of teleost terms
Teleost Anatomy Ontology
Zebrafish Anatomy
is_a
Logic implemented via Xrefs- difficult to keep synchronized
The Common Anatomy Reference Ontology
CARO is a structural classification based on
granularity
From the bottom up:
Cell component
Cell
Portion of tissue
Multi-tissue structure
From the top down:
Organism subdivision
Anatomical system
Acellular structures
Note: CARO is being updated to be more interoperable, include
logical definitions, and functional differentia
Synchronization by import across ontologies
CARO
VAO
Present TAO
Modularized ontology
One can import a whole ontology or just portions of another ontology
MIREOT: Minimum information to reference an external ontology term
Uberon – a multi-species ontology for phenomics
and evo-devo analyses
Uberon.org
Uberon classes generalize species-specific ones, and
connect to other ontologies via a variety of relations
is_a (SubClassOf)
part_of
develops_from
capable_of
is_a (taxon equivalent)
only_in_taxon
anatomical
structure
endoderm
organ part
foregut
swim bladder
organ
NCBITaxon:
Actinopterygii
respiration organ
endoderm of
forgut
respiratory
primordium
GO: respiratory
gaseous exchange
pulmonary acinus
alveolus
NCBITaxon: Mammalia
lung
alveolus of lung
MA:lung
alveolus
FMA:
pulmonary
alveolus
alveolar sac
lung primordium
lung bud
FMA:lung
MA:lung
EHDAA:
lung bud
OntoFox: a Web Server for MIREOTing
Good things:
 Based on MIREOT principle
 Web-based data input and
output
 Output OWL file can be
directly imported in your
ontology
 No programming needed
 Programmatically accessible
Improvements:
 Integration into ontology
editing tools
 More customizable
http://ontofox.hegroup.org
Proposed model moving forward
 Maintain series of ontologies at different
taxonomic levels
- euk, plant, metazoan, vertebrate, mollusc, arthropod,
insect, mammal, human, drosophila
 Each ontology imports/MIREOTs relevant subset
of ontology “above” it
- this is recursive
 Subtypes are only introduced as needed
 Work together on commonalities at appropriate
level above your ontology
Leveraging an integrated set of
ontologies
cross-ontology
link (sample)
cell
import
nervous
system
gut
circulatory
system
gland
mollusca
mantle
shell
foot
cephalopod
tentacle
brachial lobe
gonad
arthropoda
mushroom
body
mesoderm
caro / uberon/all
metazoa
drosophila
neuron types
XYZ
skeleton
appendage
respiratory
airway
muscle
tissue
larva
skeletal
tissue
vertebrata
trachea
limb
vertebra
bone
fin
tibia
vertebral
column
cuticle
antenna
tissue
parietal
bone
mesonephros
teleost
amphibia
weberian
ossicle
mammalia
mammary
gland
tibiafibula
mouse
zebrafish
NO pons
human
Not all classification is useful
About thirty years ago there was much talk that geologists
ought only to observe and not theorise; and I well remember
some one saying that at this rate a man might as well go into a
gravel-pit and count the pebbles and describe the colours.
C. Darwin
Be practical: Build ontologies for what you need and for
what can be reused
Ontologies can help reconcile annotation inconsistencies
Semantic Similarity of Phenotypes
FMA+PATO
MP
ZFA+PATO
FBbt+PATO
"Linking Human Diseases to Animal Models Using Ontology-Based Phenotype Annotation." PLoS Biol 7(11): e1000247.
doi:10.1371/journal.pbio.1000247 Washington NL, Haendel MA, Mungall CJ, Ashburner M, Westerfield M, Lewis SE
Querying for genes in similar structures across species
A
C
ascidian ampulla
sea urchin tube feet
D
B
mouse limb
polychaete parapodia
E
Vertebrata
tetrapod limbs
Ascidians
ampullae
Echinodermata
tube feet
Arthropoda
Annelida
parapodia
Mollusca
Distal-less orthologs participate in distal-proximal pattern formation and
appendage morphogenesis
Panganiban et al., PNAS, 1997
Anatomy ontologies in 2012
 Identify key points of integration between ontologies
 Modularize
based on domain
or taxon
Import and reuse
rather than crossreferencing or
“aligning”
 Let the reasoner
help do the work
 Work together
to distribute work
Reproduced with permission, Jason Freeny
http://web.mac.com/moistproduction/flash/index.html
Anatomical evidence: what is it,
and why do we care about it?
What is evidence?
ECO:000000X
Imaging assay evidence
Synaptolaemus cingulatus
AMNH 91095
OBI:Specimen
material_processing
Drawing about
anatomical entity
OBI:Image
Phenotype (character) annotation:
S. Cingulatus: mesethmoid
narrow
OBI:Conclusion
(textual entity)
Draw prepared specimen
OBI:imaging assay
cleared and stained for
cartilage and bone
OBI:processed specimen
Brian, 2008, maybe in
Venezuela
OBI: Interpreting Dataphenotypic assessment
Sidlauskas and Vari, Zoological Journal of the Linnean Society, 2008, 154, 70–210
Anatomical evidence is cumulative and synergistic
Synaptolaemus cingulatus
AMNH 91095
ECO:0000080
phylogenetic evidence
mesethmoid
narrow
ECO:0000071
morphological similarity evidence
Caenotropus maculosus
USNM 231545
mesethmoid
narrow
.
Schizodon fasciatus
INPA 21606
..
mesethmoid
wide
Brian, 2008
Phylogeny construction using
PAUP* 4.0 Beta 10
OBI: Interpreting Data
phylogeny
OBI:Conclusion
The means to the end matters
Synaptolaemus cingulatus
AMNH 91095
ECO:0000080
phylogenetic evidence
Mesethmoid
ECO:0000071
sequence similarity evidence
Caenotropus maculosus
USNM 231545
mesethmoid
narrow
.
Schizodon fasciatus
INPA 21606
..
mesethmoid
wide
Brian, 2008
Phylogeny construction using
PAUP* 4.0 Beta 10
OBI: Interpreting Data
phylogeny
OBI:Conclusion
So what should one do about
evidence?
• Keep in mind that as you record your
phenotype data, the means by which you
obtained it can matter later one
• Others may want to use your data, and they
too will care
• You may find that how you know what you
know depends on the means to the end
• You can work with ECO and OBI to get the
terms you need for your work
Acknowledgments
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Jonathan Bard
Marcus Chibucos
Wasila Dahdul
Paula Mabee
Chris Mungall
David Osumi-Sutherland
Alan Ruttenberg
Erik Segerdell
Carlo Torniai
Matt Yoder
Jie Zheng
AND numerous others
Larson, October 1987